This document provides information on acute pancreatitis including:
- The anatomy and blood supply of the pancreas.
- Risk factors, pathophysiology, clinical presentation, diagnosis and management of acute pancreatitis including determining severity.
- Choice of antibiotics and analgesics for severe acute pancreatitis, with imipenem and ciprofloxacin/metronidazole recommended for infected pancreatic necrosis.
- Novel pain management strategies like thoracic epidural analgesia and inhibitors of proteinase-activated receptors and transient receptor potential vanilloid-1 showing promise in animal models of acute pancreatitis.
2. Anatomy
Pancreas is a retroperitoneal organ 15-20 cm long and weights about 90 g.
Transversely it lies across the posterior abdominal wall posterior to the
stomach between duodenum on the right and the spleen on the left.
3.
4.
5. Relation of pancrease
Head
1. Anterior relation
transverse colon
2. Posterior relation
IVC
CBD
Right renal vein
14. Phyiology
Both exocrine and endocrine.
Composed of acinar cell[85%], islet cell[2%],ductal cell[3%],matrix[10%]
Acinar cell secret digestive enzyme .
An exocrine secretion ( pancreatic juice from the acinar cells) that enter the
duodenum through the main and accessor y pancreatic ducts.
15.
16. Why pancreatic enzyme not cause auto
digestion ?
Proenzyme
Pancreatic secretory trypsin inhibitor
Lac of alkaline medium
18. Acute pancreatitis
A clinical description of acute pancreatitis was first presented in 1652 by
the Dutch anatomist Nicholas Tulp.
Reginald Fitz of Boston presented the first systematic analyses of acute
pancreatitis In 1889.
Prevalence rate for Pancreatitis in India is 7.9 per 100,000.
20. pancreatic injury
leads to zymogen
granules and
lysosomes colocalize
inside the acinar cells.
Lysosome contains
cathepsin B
activates trypsin[in
zymogen granules ]
in these
colocalization
organelles.
Pancreatitis
activated trypsin then
induces leak of
colocalized
organelles, releasing
cathepsin B into the
cytosol.
It is the cytosolic
cathepsin B that then
induces apoptosis or
necrosis, leading to
acinar cell death.
21.
22. Risk factors
Gall Stones
40 percent .
The overall incidence of AP in patients with symptomatic
gallstone disease is 3% to 8%.
Old women
Two theory
1. Obstructive theory.
2. Reflux theory.
23. Alcohol
35 percent .
heavy ethanol abuse (>100 g/day for at least 5 years)
However, only 5% to 10% of patients who drink alcohol
develop AP.
Young men
Smoker .
Mechanism
1. Decrease pancreatic perfusion.
2. Sphincter of Oddi spasm.
3. Obstructs pancreatic ducts through the precipitation of
proteins inside the ducts.
4. fatty acid ethyl esters, cause fragility of zymogen granules
and lysosomes, which leads to abnormal pancreatic enzyme
activation inside acinar cells
5. Ethanol activates PSCs and induces pancreatic fibrosis.
25. ERCP
AP is the most common complication after
ERCP,
occurring in up to 5% of patients.
AP occurs more frequently in patients who
have undergone therapeutic procedures
compared with diagnostic procedures.
Clinical course mild .
28. Other
Autoimmune pancreatitis
Viral infections (mumps, coxsackie B)
Fungul infection[ aspergillus ]
Scorpion bite - Italian scorpion('l'ityus trimtatis)
MOA: Neurotransmitter discharge from cholinergic
nerve terminals, massive production of pancreatic juice
Idiopathic
Intraoperative injury or handling
Trauma
29. Clinical menifestion
ABDOMINAL PAIN
SITE : usually experienced first in the epigastrium but may be localized to either upper
quadrant or felt diffusely throughout the abdomen or lower chest
ONSET: characteristically develops quickly, generally following substantial meal
SEVERITY: frequently severe, reaching max. intensity within minutes
NATURE: "knifing" burning
DURATION: hours-days
COURSE: constant (refractory to usual doses of analgesics, not relieved by vomiting)
RADIATION : directly to back(50%), chest or flanks
AGGRAVATING FACTOR: food/alcohol intake, walking, lying supine.
RELEIVING FACTOR: sitting or leaning/stooping forward (MUHAMMEDAN
30.
31. Associative symptoms
Nausea, frequent and effortless vomiting, Due to reflex pylorospasm
Persistent retching despite empty stomach
Hiccups Due to gastric distension/diaphragmatic irritation
Fever
Weakness, Anxiety, Sweating
dehydration
36. Pancreatic Enzymes' Assays
Serum Amylase:
ONSET: almost immediately
PEAK: within several hours
3-4 times upper limit of normal within 24 hrs (90%)
RETURN to normal depends on severity(3-5 days)
Also raise in SBO, appendicitis, peptic perforation, mesenteric ischemia,
torsion of ovary, ruptured ectopic pregnancy
Serum Lipase:
more sensitive/specific than amylase
Remains elevated longer than amylase(12 days)
Useful if late presentation
37. Imaging studies
X-ray FPA
1. Sentinel loop sign
Localized isolated Distended gut loop (Ileus) seen near the site of injured viscus
or inflamed organ
SITE.
Acute Pancreatitis* Left hypochondrium (PROXIMAL JEJUNUM)
Acute Appendicitis* Right iliac fossa
Acute Cholecystitis* Right Hypochondrium
Diverticulitis* Left iliac fossa
Not diagnostic of Acute Pancreatitis; useful in differential diagnosis
38.
39.
40. 2. Colon cut-off sign
Gas filled (Distended) segment of proximal(mainly transverse) colon associated
with narrowing of the splenic flexure with collapse of descending colon
41. 3. OTHERS
Obliteration of psoas shadow
Localized ground glass appearance ( localized increased high soft
tissue density)
Calcified gall stones
Pancreatic calcification(chronic pancreatitis)
Air in the duodenal C-loop
For DD of perforation peritonitis
42.
43.
44. USG
Not diagnostic
Should be performed within 24 hours in all patients to detect gall stones*
as a potential cause .
Rule out acute cholecystits as differential diagnosis
Detect dilated CBD
sensitivity-(70-80%)
45. CECT Abdomen
IOC
Detect pancreatic necrosis (patients with suspected severe pancreatitis).
Detect complications of AP.
Diagnose conditions mimicking AP, including
gastrointestinal ischemia, ulceration, or perforation
90% sensitivity and specificity
Normal pancreas enhance uniformaly.
Pancreatic duct appear linear non enhancing structure
46.
47.
48.
49.
50.
51.
52. Magnetic Resonant Imaging
Suitable alternative to CT in patients with a contrast allergy and renal
insufficiency where T2-weighted images without gadolinium contrast can
diagnose pancreatic necrosis
Magnetic Resonant
Cholangiopancreatography
INDICATION:
diagnosis of suspected biliary and pancreatic duct obstruction in the setting of
pancreatitis.
Repeated attacks of idiopathic acute pancreatitis
54. Endoscopic Retrograde
Cholangiopancreatography
INDICATION
Severe gallstone AP or AP with concurrent acute
cholangitis/biliary obstruction/ biliary sepsis/jaundice
(due to persistent stone)
ERCP within 24(-72) h of admission
Sphincterotomy/stent and bile duct clearance reduces
infective complications/mortality
55. Assessment of Severity of Disease
Ranson criteria
11 parameters
3 or more
PPV 50%
NPV 90%
56.
57. Drawbacks
1. it does not predict the severity of disease at the time of the admission
because six parameters are assessed only after 48 hours of admission.
2. it is mainly used to rule out severe pancreatitis or to predict the risk of
mortality
3. Different for gall stone and alcoholic pancreatitis .
58. Acute Physiology and Chronic Health
Evaluation (APACHE II) score
12 PARAMETERS
An APACHE II score of 8 or higher defines severe pancreatitis.
The main advantage is that it can be used on admission and repeated at
any time.
However, it is complex, not specific for AP, and based on the patient’s age,
which easily upgrades the AP severity score.
59.
60. Management
Mild or moderate acute Pancreatitls
self-limiting, needing only brief hospitalization.
Rehydration by IV fluids
Frequent non-invasive observation/monitoring(atleast 8 hrly)
Brief period of fasting till pain/vomiting settles
No medication required other than analgesics and anti-emetics
Antibiotics not indicated in absence of signs or documented sources of
infection
Correction of electrolyte imbalance
61. Severe acute pancreatitis
SAP is characterized
by the presence of
organic failure
(Ranson ≥ 3 or
APACHE II ≥ 8), or
local complications
such as necrosis,
pseudocyst and
abscess
62. Antibiotics
Routine use NOT recommended as Prophylaxis in severe AP as Prevenitve
measure in sterile necrosis to prevent development of infected necrosis
Indicated in Established infected pancreatic necrosis or Extraperitoneal
infections ,Cholangitis, catheter-acquired infections, bacteremia, UTIs,
pneumonia
C-reactive protein is a sensitive marker of pancreatic necrosis and it starts
to increase significantly 48 hours after the onset of symptoms. Thus, C-
reactive protein can be useful in the identification of patients with high
possibility to develop necrosis, in particular when the value is over 150
mg/dl, and subsequently define which patients are candidates to receive
early antibiotics
63. The main arguments against the use of antibiotics are the increase of fungal
infection, and the increase of bacteria resistance,
One paper analyzing data of 46 patients with infected pancreatic necrosis
receiving antibiotics showed that 17 (37%) of them developed fungal
infection.
International Association of Pancreatology guidelines for the management of
AP recommends the use of prophylactic broadspectrum antibiotics to reduce
infection rates in CT-proven necrotizing pancreatitis
Although there is no support in the literature, it is reasonable to assume that
prophylactic antibiotic therapy should be considered only for patients with
more than 30% pancreatic necrosis. In contrast, there is no evidence in the
literature that the use of antibiotics in the absence of necrosis is beneficial.
64. Which antibiotic?
Two main aspects must drive the choice of the antibiotics: the flora and the
penetration in the pancreatic tissue.
The bacteria most frequently found are E. coli (27–35%), Enterococcus (24–
26%), Staphylococcus aureus (14–16%), Staphylococcus epidermidis (15%),
Klebsiella (15%) Pseudomonas sp (7–11%) and Streptococos (4–7%)
Experimental studies were performed to determine which antibiotic would
have a better pancreatic concentration
Poor penetration Medium penetration Good penetration
Netilmicin Mezlocillin Ciprofloxacin
Tobramicin Piperacillin Ofloxacin
Ceftizoxime Imipenem
Cefotaxime Metronidazole
65. Based on studies and guidelines, conclude that the recommended
antibiotic in AP is Imipenem 3 × 500 mg/day i.v. Alternatively, the use of
Ciprofloxacin 2 × 400 mg/day i.v. associated with Metronidazole 3 × 500
mg/day i.v. can also be considered.
66. Best painkiller in pancreatitis ?
The WHO analgesia ladder was
originally developed to treat
pain due to cancer. However,
over time, the indications have
been extended, and the medical
management of pain in acute
pancreatitis
67. Opioid analgesics, especially morphine, were long blamed to cause dysfunction of the
sphincter of Oddi after systemic administration. However, several studies showed that
morphine has no proven significantly unfavorable influence on the course of AP (
the latest studies including systematic reviews convincingly demonstrated that opioid
analgesics could be safely administered with major benefit in AP, and that the dogma of
“no opioids in AP” should be considered to be obsolete
metamizole resulted in somewhat more frequent and quicker pain relief than s.c.
morphine
pethidine
tramadol
buprenorphine as a longer-acting analgesic has a similar analgesic capacity as
pethidine, but a lower potential to cause physical opioid dependence
68. An interesting question on the interaction of pain with nutrition in AP is
related to pain relapse after oral refeeding during AP. In different studies,
the incidence of pain onset or exacerbation after refeeding ranged
between 21-25% and reached a maximum between 50-100% of cases
within 48 h of refeeding (59). Therefore, the incidence of pain relapse after
oral refeeding during AP seems to be quite high (59). Current evidence
suggests that nutrition support should only be performed in patients with
severe pancreatitis, whereas nutrition support is generally not needed in
patients with mild or moderate disease where oral feeding should be
started as soon as possible and as tolerated by patients. If nutrition
support is needed in these patients, enteral nutrition should be preferred
over parenteral nutrition. However, a clear consensus on how and when
the oral refeeding should be initiated has not yet been reached.
69. Novel Strategies of Pain Management in AP
recently reported improved survival owing to thoracic epidural analgesia (TEA) in a
animal AP model. Here, the 7-day-survival rate of animals that received bupivacaine
as TEA was 82% when compared to a mere 29% in the control group.
inhibitors of the proteinase-activated-receptor-2 (PAR2), or of the transient receptor
potential vanilloid-1 (TRPV1) have been shown to be beneficial for treating pain during
experimental AP in mice
Recently, blockade of interleukin-6 (IL-6) signaling by an orally available, small-
molecule IL-6 receptor inhibitor was shown to diminish abdominal hyperalgesia during
AP
nitric oxide synthase (NOS) inhibitors reduced abdominal hyperalgesia and AP-
associated during AP in rats.
a multicentre randomized controlled trial of magnesium sulphate in the prevention of
post-ERPC pancreatitis shall provide data on the impact of magnesium on pain
sensation during post-ERCP pancreatitis (26). Once shown to be effective, beyond its
preventive usage, magnesium may be considered a novel analgesic alternative to treat
pain in AP
70. Nutrition
In mild AP
oral feedings can be started immediately if there is no nausea/vomiting,
and the abdominal pain/tenderness/lleus has resolved
Initiation of feeding with a small and slowly increasing low-fat (low-
protein) soft diet
In severe AP
Enteral route is recommended to prevent infectious complications
Parenteral nutrition should be avoided, unless enteral route is not
available, not tolerated, or not meeting caloric requirements
71. Role of Surgery in pancreatitis
In case of mild gallstone AP, cholecystectomy should be performed before
discharge to prevent a recurrence of AP
In case of necrotizing biliary AP, in order to prevent infection,
cholecystectomy is should be done after 6 week.
If patient unfit for surgery(comorbid/elderly), biliary sphincherotomy alone
may be effective to reduce further attacks of AP
72. Complication of acute pancreatitis
Most common complication – peripancreatic fluid collection
Most common metaboloc complication – hypocalcemia
1. Peripancreatic fluid collection [30 to 57%]
not covered with epithelium or capsule
treatment –conservative
2. Pancreatic necrosis - Pancreatic necrosis is the presence of nonviable
pancreatic parenchyma.
20%
Complication -infection
73.
74. Infected pancreatic necrosis should be suspected in patients with
prolonged fever, elevated white blood cell count,
CECT is the most reliable technique to diagnose pancreatic necrosis. It is
typically seen as areas of low attenuation. Evidence of air within the
pancreatic necrosis seen on a CT scan confirms the diagnosis but is a rare
finding.
75. Management
FNA with culture and sensitivity .
Historically, the definitive treatment of infected pancreatic necrosis was surgical
debridement with necrosectomy, but mortality was very high .
As a result of the elevated morbidity and mortality rates with open debridement,
endoscopic and laparoscopic techniques are being used more often.
Timing of debridement
The optimal timing is at least 3-4wks following the onset of acute pancreatitis.
Delayed debridement allows
–clinical stabilization of the patient
–resolution of early organ failure
–decreased inflammatory reaction, and
necrotic areas are demarcated
76. 3.Pancreatic pseudocyst
By definition, the capsule of a pseudocyst is composed of collagen and
granulation tissue, and it is not lined by epithelium.
location-Lesser peritoneal sac in proximity to the pancreas Large pseudocysts
can extend into the paracolic gutters, pelvis
Pathophysiology
Pancreatic necrosis causes ductular disruption, resulting in leakage of
pancreatic juice from inflamed area of gland, accumulates in space
adjacent to pancreas Inflammatory response induces formation of distinct
cyst wall composed of granulation tissue, organizes with connective tissue
and fibrosis
5% to 15%
84. When to Discharge
Pain is well controlled with oral analgesia
Able to tolerate an oral diet that maintains their caloric needs, and
all complications have been addressed adequately
Follow up
Routine clinical follow-up care (typically including physical examination
and amylase and lipase assays) is needed to monitor for potential
complications of the pancreatitis Within 7-10 days