2. Pancreas is both a digestive
organ as well as an endocrine
gland located
reteroperitoneally in
between 1st
and 3rd
part of
duodenum, subserving
following 3 important
functions:
◦ neutralize chyme
◦ digestive enzymes
◦ hormones
5. COMPARTMENTALIZATION - digestive enzymes are contained
within zymogen granules in acinar cells
REMOTE ACTIVATION - digestive enzymes are secreted as
inactive proenzymes within the pancreas
PROTEASE INHIBITORS – pancreatic secretory trypsin inhibitor
(PSTI or SPINK1) is secreted along with the proenzymes to
suppress any premature enzyme activation.
AUTO “SHUT-OFF” – trypsin destroys trypsin in high
concentrations
Production of non specific antiproteases like alpha 1
antitrypsin and alpha 2 macroglobulin
6. Acute pancreatitis is the acute inflammatory process of pancreas
with variable involvement of other regional tissues or remote organ
systems.
Clinically defined by 2 out of 3 criteria
1. Symptoms,such as epigastric pain, consistent with the disease.
2. Serum amylase or lipase greater than 3 times the normal upper limit.
3. Radiological imaging consistent with the diagnosis using CT or MRI.
in case of acute pancreatitis Pancreatic function and morphology
return to normal after (or between) attacks
7. Various theories suggesting pathogenesis of acute
pancreatitis are :
1. Colocalisation of lysosomal hydrolases e.g cathepsin B
with trypsinogen leading on to its conversion to active form.
2. pancreatic injury may lead to altered secretion of activated
proteases or their proenzymes through the basolateral
membranes of the acinar cells followed by their leakage
into the interstitium . Enhanced pancreatic ductal
permeability allows activated enzymes to leak from the
duct and initiate pancreatic autodigestion.
8. 3. oxygen radicals released secondary to pancreatic injury can
cause inactivation of circulating protease inhibitors, thereby
contributing to the accumulation of activated proteases in
pancreatic tissue.
4. Reflux of bile in to the pancreatic duct or increased pancreatic
pressure because of the obstruction at the ampulla caused by
gall stones may lead on to leakage of proteases .
5. Numerous genetic mutations causing premature activation of
pancreatic zymogens within the pancreas also have been
proposed as part of the pathogenetic mechanism for hereditary
pancreatitis. e.g. Mutations in the cystic fibrosis
transmembrane conductance regulator (CFTR) and PSTI or
SPINK1.
9. All the above proposed mechanisms ultimately lead on to activation
of Proteolytic enzymes in the pancreas rather than in the intestinal
lumen. These enzymes cause auto digestion of pancreatic tissue
leading to the activation of inflammatory cascade.
Activating factors for these proenzymes are:
Endotoxins, Exotoxins,Viral infections, Ischemia, Anoxia, Direct
trauma, Activated proenzyme (e.g trypsin).
10. INITIAL PHASE
◦ acinar cell injury due to intrapancreatic digestive
enzyme activation
◦ Zymogen activation mediated by lysosomal
hydrolases e.g. cathepsin B
SECOND PHASE
◦ Intrapancreatic inflammation reaction
◦ Due to activation, chemoattraction, and
sequestration of neutrophils in the pancreas
* This neutrophil sequestration can activate trypsinogen
13. Anti HIV medication: Lamivudine,
didanosine, nelfinavir
Anti microbials:
dapsone,isoniazid,rifampin,penta
midine,pentavalent
antimonials,tetracyclines,erythrom
ycin,metronidazole,
Antihypertensives: ace inhibitors,
losartan, Furosemide,
Hydrochlorothiazide,alphamethyld
opa
Analgesics:
Acetaminophen,sulindac
IBD:
mesalamine,5ASA,sulfasalazine
Anti cancer drugs: L-Asparaginase,
6-Mercaptopurine, Cytosine
arabinoside
Steroids: Dexamethasone,
hydrocortisone,estrogen
Neuropsychiatric drugs:
valproate,carbamazapine,topiram
ate,clozapine
Others: Carbimazole,
methimazole,
Pravastatin,simvastatin Procainam
ide
Azathioprine, interferon alpha
14. Pain : Major symptom
◦ Vary from mild to severe,
constant pain
◦ Steady and boring in character
◦ Located in epigastrium and
periumbilical radiating to the
back
◦ Chest, flank and lower
abdomen
◦ Pain more intense on supine,
relieved by sitting
15. Nausea, vomitting, abdominal distention
Low grade fever, tachycardia, hypotension
Shock, jaundice
Erythematous skin nodules
In 10-20% of patients- basilar rales, atelectasis, and
pleural effusion
Bowel sounds usually diminished or absent
Palpable enlarged pancreas, or a pseudocyst in the upper
abdomen
Cullen’s Sign; grey turner sign; fox sign
17. Grünwald sign (appearance of ecchymosis, large bruise,
around the umbilicus due to local toxic lesion of the
vessels)
Körte's sign (pain or resistance in the zone where the
head of pancreas is located (in epigastrium, 6–7 cm
above the umbilicus))
Kamenchik's sign (pain with pressure under the
xiphoid process)
18. Mayo-Robson's sign (pain while pressing at the top of the
angle lateral to the Erector spinae muscles and below the
left 12th rib (left costovertebral angle (CVA))[2]
Mayo-Robson's point - a point on border of inner 2/3 with
the external 1/3 of the line that represents the bisection
of the left upper abdominal quadrant, where tenderness
on pressure exists in disease of the pancreas. At this point
the tail of pancreas is projected on the abdominal wall.
20. 1. History and physical
examination
Showing features consistent
with the diagnosis of ac.
Pancreatitis as discussed
in previous slides
1. Laboratory tests
2. Imaging studies
21. Serum amylase
Elevates within HOURS and can remain elevated for 4-5
days
High specificity when using levels >3x normal
Many false positives (see next slide)
Most specific = pancreatic isoamylase (fractionated
amylase
Normal values of serum amylase are 30-110IU/L
23. Serum lipase
The preferred test for diagnosis
Begins to increase 4-8H after onset of symptoms and
peaks at 24H
Remains elevated for days
Sensitivity 86-100% and Specificity 60-99%
>3X normal S&S ~100%
Normal levels of serum lipase are 5-208 u/l
24. Trypsinogen 2
◦ Excreted into the urine
◦ Used as a screening test for acute pancreatitis
Trypsinogen activated peptide
◦ Small peptide
Advantage
◦ Appear very early during the disease
Disadvantage
◦ Limited "diagnostic window".
decrease very quickly irrespective of the course of the disease
◦ Not suitable for rapid simple analysis
25. • Elevated ALT > 3x normal (in a non-alcoholic) has a positive predictive value of
95% for GS pancreatitis
• newer diagnostic tests like Serum Neutrophil –elastase,IL-6, and alpha
macroglobulin , urinary trypsinogen activated peptide, polymorphonuclear
leucocyte esterase have also been used in diagnosing acute pancreatitis.
Other tests used to determine prognosis include wbc count(15,000-20,000
leukocytes/ microliter)
( Hct > 44%)
Plasma glucose
Serum calcium
CRP(normal values are 10-21 mg/dl)
LDH levels
Serum triglycerides
ECG: ST segment and T wave abnormalities due to changes in vagal nervous
system and visceral venous thrombosis
26. Plain xray abdomen shows
1. Air in duodenal c loop
2. Colon cut off sign which represents distention of the
colon up to the transverse colon with a paucity of gas
distal to the splenic flexure.
3. The sentinel loop sign, which represents a focal dilated
proximal jejunal loop in the left upper quadrant
USG abdomen : mainly helpful in diagnosing gall stones
and pseudopancreatic cyst. It can also be used for fine
needle aspiration of the fluid collection in pancreatitis
28. CT
◦ Excellent in pancreas imaging
◦ Recommended in all patients with persisting organ
failure, sepsis or deterioration in clinical status (6-10
days after admission)
◦ Necrosis will be present at least 4 days after onset of
symptoms; if CT is ordered too early it will
underestimate severity
◦ Follow-up months after presentation as clinically
warranted for CT severity index of >3
29. Transverse CT scan obtained with intravenous and oral contrast material reveals
a large, edematous, homogeneously attenuating (73-HU) pancreas (1) and
peripancreatic inflammatory changes (white arrows). Although the
attenuation values are low, there is no pancreatic necrosis. Calcified
gallstones are seen in gallbladder (black arrow). 2 = liver (140 HU
30. MRI/MRCP newest “fad”
◦ Decreased nephrotoxicity from gadolinium
◦ Better visualization of fluid collections
◦ MRCP allows visualization of bile ducts for stones
Does not allow stone extraction or stent insertion
EUS(endoscopic ultrasonography)
◦ EUS is equal to MRCP and ERCP but far more sensitive
than either abdominal ultrasonography or CT in detecting
common duct stones.
◦ It might be the best method of evaluating bile duct in a
patient with acute necrotising pancreatitis
31. Biliary pancreatitis
Amylase Usually > 1000
IU
AST, ALT Acute elevation
with rapid resolution
Alkaline phosphatase and
bilirubin Increased
Ultrasound Gallstones,
dilated common bile duct
CT scan Gallstones,
dilated common bile duct
Alcoholic pancreatitis
S. amylaseUsually < 500
IU
AST,ALT Minimal
elevation that does not
fluctuate
ALP Not usually elevated
USG shows Changes of
chronic pancreatitis
Pancreatic calcifi cation,
dilated pancreatic duct
with stones
32.
33. AT ADMISSION
1. Age > 55 years
2. WBC > 16,000
3. Glucose > 200
4. LDH > 350 IU/L
5. AST > 250 IU/L
WITHIN 48 HOURS
1. HCT drop > 10
2. BUN > 5
3. Arterial PO2 < 60 mm Hg
4. Base deficit > 4 mEq/L
5. Serum Ca < 8
6. Fluid sequestration > 6L
34. AT ADMISSION
1. Age > 70 years
2. WBC > 18,000
3. Glucose > 220
4. LDH > 400 IU/L
5. AST > 250 IU/L
WITHIN 48 HOURS
1. HCT drop > 10
2. BUN > 5 after iv fluid
rehydration
3. Arterial PO2 < 60 mm Hg
4. Base deficit > 5 mEq/L
5. Serum Ca < 8
6. Fluid sequestration > 4L
35. Though ransons criteria is an excellent prognostic tool, but
it has 2 disadvantages:
◦ It can not be used with in 24 hrs of admission
◦ It is cumbersome though less as compared to apache II
score
39. 1. WBC > 15,000
2. Glucose > 180
3. BUN > 16
4. Arterial PO2 < 60 mm Hg
5. Ca < 8
6. Albumin < 3.2
7. LDH > 600 U/L
8. AST or ALT > 200 U/L
40. SIRS: systemic inflammatory
response syndrome is said to
be present if 2 of the
following criteria are full
filled:
1. Heart rate > 90 beats/minute
2. Core temperature <36°C or
>38°C
3. White blood count <4000
or >12000/mm3
4. Respirations >20/min or
PCO2 <32 mm Hg
41. CT Grade (balthazar grade)
◦ Normal 0 points
◦ Focal or diffuse enlargement 1 point
◦ Intrinsic change or fat stranding 2 points
◦ Single ill-defined fluid collection 3 points
◦ Multiple collections of fluid or gas 4 points
Necrosis Score
◦ None 0 points
◦ 1/3 of pancreas 2 points
◦ 1/2 of pancreas 4 points
◦ > 1/2 of pancrease 6 points
Severe = Score > 6 (CT Grade + Necrosis)
42.
43. Mild acute pancreatitis
▸ No organ failure
▸ No local or systemic
complications
Moderately severe acute
pancreatitis
▸ Organ failure that
resolveswithin 48 h (transient
organfailure) and/or
▸Local or systemic complications
without persistent organ failure
Severe acute pancreatitis
▸ Persistent organ failure (>48 h)
–Single organ failure
–Multiple organ failure
44.
45. Local complications
Necrosis Sterile, Infected, Organized
Pancreatic fluid collections •Peripancreatic fluid collections
•Pancreatic Pseudocyst causing pain,
rupture, hemorrhage, infection,Obstruction
of GIT .
•Acute necrotic collection
•Walled off necrosis
Pancreatic ascites Disruption of main pancreatic duct
Leaking pseudocyst
Involvement of contiguous organs by
necrotizing pancreatitis
Massive intraperitoneal hemorrhage
Thrombosis of blood vessels
Bowel infarction
Obstructive jaundice
46. Necrotizing pancreatitis
◦ severe form of acute
pancreatitis,
◦ increasing abdominal pain,
fever,
◦ marked leukocytosis,
◦ and bacteremia
Shown in cect as area
Of non enhancement
It can get infected or remain
sterile
47. APFC(acute peripancreatic fluid collection): Peripancreatic
fluid associated with interstitial oedematous pancreatitis with no
associated peripancreatic necrosis. This term applies only to areas of
peripancreatic fluid seen within the first 4 weeks after onset of
interstitial oedematous pancreatitis and without the features of a
pseudocyst.
Pseudocyst: An encapsulated collection of fluid with a well defined
inflammatory wall usually outside the pancreas with minimal or no
necrosis. This entity usually occurs more than 4 weeks after onset of
interstitial oedematous pancreatitis to mature.
Acute necrotic collection: 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.
48. Walled of necrosis: A mature, encapsulated collection of
pancreatic and/or peripancreatic necrosis that has developed a well
defined inflammatory wall. WON usually occurs >4 weeks after onset
of necrotising pancreatitis.
Pancreatic pseudocyst Walled of necrosis
49. Systemic
complications
Pulmonary Pleural effusion, Atelectasis, Mediastinal abscess, Pneumonitis,
ARDS
Cardiovascular Hypotension, Hypovolemia, Sudden death, Nonspecific ST-T
changes in ECG, pericardial effusion
Hematologic DIC
GI Hemorrhage PUD, Erosive gastritis, Hemorrhagic pancreatic necrosis with
erosion into major BV, Portal vein thrombosis, Variceal
hemorrhage
Renal Oliguria, Azotemia, Renal artery and/or vein thrombosis, Acute
tubular necrosis
Metabolic Hyperglycemia, Hypertriglyceridemia, Hypocalcemia,
Encephalopathy, Sudden blindness (Purtscher’s retinopathy
Central Nervous System Psychosis, Fat emboli
Fat necrosis Subcutaneous tissues, Bone
50. Pulmonary: ARDS
◦ damage to the pulmonary surfactant layer by circulating
phospholipase A and free fatty acids
Cardiovascular: Circulatory shock
◦ a combination of volume depletion and hyperdynamic
circulatory state with decreased peripheral vascular
resistance
• Renal: Acute renal failure
– caused by circulatory shock and a selective increase in renal
vascular resistance
51. • GI: Hemorrhage
– erosion of the splenic or gastroduodenal arteries.
– diffuse mucosal bleeding from the antrum and
duodenum
– perforation of peripancreatic inflammation into any
portion of the gastrointestinal tract from esophagus to
colon.
– Splenic involvement by direct extension of the
inflammatory process or, secondarily, by splenic vein
thrombosis, which leads to gastric fundic varices.
52.
53. 1. Conventional measures:
Analgesics- to reduce pain, opiates like morphine,
tramadol, meperadine can be given. phentanyl has also
been tried by s/c and i/v route.
Patient is to be kept nill per oral
I/V fluids : early rigorous intravenous hydration is
important in preventing complications. 3-4 litres fluid
daily the form of crystalloids like RL, DNS has been
recommended. Or maintain urine output at 40-50 ml/hr
Oxygen inhalation ideally should be given to all patients
with acute severe pancreatitis.
54. 2. Diet and nutrition:
Patient is to be kept on I/V fluids initially, but can be
considered for early refeeding if:
Resolution or decreased abdominal pain
Patient is hungry
No signs of any organ dysfunction
Enteral feeding is superior to total parentral nutrition.not
much difference has been found between NG and NJ
feeding.
Start early refeeding with low fat high carb liquid diet
55. 3. Antibiotics
These are usually not indicated in mild acute pancreatitis because
of the risk of super infectionand development of resistance.
Can be given for prophylaxis in severe necrotising pancreatitis
and in treatment of infective necrosis
Organisms implicated in acute pancreatitis are usually were gram-
negative aerobic or anaerobic species (E.coli, Pseudomonas
aeruginosa, Proteus species, K. pneumoniae), with occasional
gram positives S. faecalis, Staph aureus, S viridans,
Staphylococcus epidermidis) and rare fungi (Candida species)
56. Antibiotics contd.
The antibiotics found to have maximum penetration in the
necrotic pancreatic tissue as well as having maximum
activity against the causative organisms are imipenem,
fluoroquinolones (ofloxacin,pefloxacin and ciprofloxacin)
and metronidazole.these antibiotics can be used for a
period of 7-21 days.not much benefit has been obtained
by a shorter or a longer course of therapy.
57. Endoscopic and surgical interventions
1. Sphincterotomy for gall stone pancreatitis
2. Pancretic duct stent placement to prevent pacreatic fluid
leakage
3. Necrosectomy mainly for infected necrosis or in cases of
sterile necrosis not accepting orally
4. Early cholecystectomy for gall stone pancreatitis
5. Percutaneous catheter drainage of necrotic material
58. Other modalities of treatment
1. Protease inhibitors (aprotinin, gabexate, mesilate) have
shown some positive results in few clinical trials
2. Platlet activating factor inhibitor (lexipafant)
3. antisecretory agents (somatostatin, octreotide): not
of much benefit
4. Probiotics have rather shown negative results in
some of the trials
59. Early course-0-72 hrs
Is there organ failure
NO
•Admission to ward
•NPO
•Pain control
•I/V hydration
•Nasal oxygen
•Regular hct,electrolyte
YES
•Admission to icu
•Same orders as ward admission
•Assisted ventilation if needed
•Assess for bile duct obstruction
•For jaundice – urgent ercp
60. YES
Later course > 72 hrs
Evidence of severe dis. Or
organ failure
Early refeeding
Evaluate for etiology
If GS early cholecystectomy
NO
Observe for biliary sepsis-
urgent ercp
Enteral feeding(NJ or NG)
CT to evaluate for necrosis
Consider antibiotic if
infective necrosis suspected
61. Late course : 7-28 days
Patient improving?
yes
Consider oral
refeeding
If on antibiotics, consider
FNAC of pancreas for culture
and change of antibiotics
If not on antibiotics and fnac
negative than keep off
antibiotics
no
62. Beyond 28 days
Patient improving?
Consider refeeding
If patient can not
tolerate feeding consider
necrosectomy
yes
Consider necrosectomy
by
endoscopic,radiological
or surgical means
no
63. The mortality rate in cases of mild acute pancreatitis is
around 5% whereas for severe necrotising pancreatitis
it may be as high as 30-70%.this warrants for timely
diagnosing and efficiently managing acute pancreatitis
so as to prevent complications and decrease mortality.
Many newer techniques for management of acute
pancreatitis are emerging, but the most important way
of reducing morbidity and mortality by this painful
disease is to attain healthy life style and abstain from
alcohal(the 2 most common causes of ac. Pancreatitis.)
