Acute pancreatitis is defined clinically by abdominal pain consistent with pancreatitis along with elevated serum amylase or lipase levels and imaging findings. It has an incidence of 4.9 to 73.4 per 100,000 patients in the US. The natural history involves an initial inflammatory phase lasting about a week followed by potential complications like pancreatic necrosis in 20% of patients. The pathogenesis involves inappropriate activation of digestive enzymes within the pancreas. Common causes include gallstones, alcohol use, hypertriglyceridemia, and post-ERCP. Diagnosis relies on abdominal pain and at least a 3-fold elevation of serum amylase or lipase.

2. Acute pancreatitis
• Presented by :Naser Ahmad Mohammadi
• Date :06/06/1399
• Venue:Mehraban hospital conference room
• Duration:40 minutes

3. References
1. Sleisenger and Fordtran's Text book of Gastroenterology&Hepatology
2. UpToDate
3. UK guidelines for the management of acute pancreatitis

4. Definition
acute pancreatitis is best defined clinically by a patient presenting with 2
of the following 3 criteria:
(1) symptoms (e.g., epigastric pain) consistent with pancreatitis
 (2) a serum amylase or lipase level greater than 3 times the laboratory’s
upper limit of normal
 (3) radiologic imaging consistent with pancreatitis, usually using CT or MRI

7. INCIDENCE
• The incidence of acute pancreatitis in the United States varies from
4.9 to 73.4 per 100,000 patients.

8. NATURAL HISTORY
Acute pancreatitis appears to have 2 distinct phases.
• The first is related to the pathophysiology of the inflammatory cascade.
• The second, which develops in fewer than 20% of patients with acute
pancreatitis, is related to the anatomic complications that develop, such as
pancreatic necrosis.
• The first phase usually lasts 1 week. During this phase, the severity of acute
pancreatitis is directly related to extra pancreatic organ failure.

9. • Approximately 75% to 80%, of patients with acute pancreatitis have a resolution
of the disease process (interstitial pancreatitis) and do not enter the second
phase.
• However, in close to 20% of patients, a more protracted course develops, often
related to the necrotizing process (necrotizing pancreatitis) lasting weeks to
months.
• There are 2 time peaks for mortality in acute pancreatitis.
• Most studies in the United States and Europe reveal that about half the deaths
occur within the fist week or 2, usually from multi organ failure.
• Death can be very rapid. About one quarter of all deaths in Scotland occurred
within 24 hours of admission, and one third within 48 hours.

11. PATHOGENESIS AND PATHOPHYSIOLOGY
• Acute pancreatitis occurs when there is abnormal activation of
digestive enzyme within the pancreas . This occurs through
inappropriate activation of inactive enzyme precursors called
zymogens (or proenzymes) inside the pancreas,most notably
trypsinogen.

13. Gallstones
• The most common obstructive process leading to pancreatitis is gallstones which
cause approximately 40% of cases of acute pancreatitis.
• However, only 3% to 7% of patients with gallstones develop pancreatitis.
• Gallstone pancreatitis is more common in women than men because gallstones
are more frequent in women.
• Acute pancreatitis occurs more frequently when stones are less than 5 mm in
diameter

14. Biliary Sludge and Microlithiasis
• Biliary sludge is a viscous suspension in gallbladder bile that may contain small ( <3
mm) stones (i.e., microlithiasis).
• Cephalosporin antibiotic ceftriaxone can form a sludge within the biliary system when
its solubility in bile is exceeded; this process rarely causes stones.
• Sludge disappears after stopping the drug.
• Commonly, biliary sludge is found in patients with idiopathic acute pancreatitis.
• However, the association between biliary sludge and acute pancreatitis is unproved.

15. Alcohol and Other Toxins
Ethyl Alcohol
• Alcohol causes at least 30% of cases of acute pancreatitis.
• Alcohol is the most common etiology of chronic pancreatitis in developed
countries.
• Interestingly, only 10% of chronic alcoholic patients develop chronic pancreatitis
• Possible mechanisms of alcohol-related injury, including perturbations in
exocrine function, changes in cellular lipid metabolism, induction of oxidative
stress.

16. Tumors
• Tumors, presumably by obstructing the pancreatic duct, can cause recurrent acute
pancreatitis, especially in individuals older than age 40.
• The most common tumor that presents in this manner is intra ductal papillary
mucinous neoplasm (IPMN).
• Pancreatic adenocarcinoma can also present as acute pancreatitis in a small
percentage of patients.
• Metastases from other cancers (lung, breast) to the pancreas have also caused
pancreatitis

17. Drugs
• Medications are an infrequent but important cause of acute pancreatitis.
• Although there are reports that drug-induced acute pancreatitis accounts for 1% to 4%
of all cases.
• Drug-induced pancreatitis tends to occur within 4 to 8 weeks of beginning a drug.
• There are several potential pathogenic mechanisms of drug-induced pancreatitis.

18. • pancreatitis recurs within hours to days. Examples of drugs that operate
through this mechanism are aminosalicylates, metronidazole, and tetracycline.
• The second mechanism is the presumed accumulation of a toxic metabolite that
may cause pancreatitis, typically after several months of use. Examples
of drugs in this category are valproic acid and didanosine
• Drugs that induce hypertriglyceridemia (e.g., thiazides, isotretinoin, tamoxifen).
• Finally, a few drugs may have intrinsic toxicity wherein an overdose can cause
pancreatitis (erythromycin, acetaminophen).

20. Hypertriglyceridemia
• Hypertriglyceridemia is perhaps the third most common identifiable cause of
pancreatitis after gallstones and alcoholism
• Accounting for 2% to 5% of cases.
• Hypertriglyceridemia is also implicated in more than half of gestational
pancreatitis case
• Serum TG concentrations above 1000 mg/dL (11 mmol/L) may precipitate attacks
of acute pancreatitis.
• However, recent studies suggest that the serum TGs may have to be even higher
to precipitate acute pancreatitis
• Perhaps above 2000 mg/dL, and with obvious lactescent (milky) serum due to
increased concentrations of chylomicrons.

21. Post-ERCP
• Acute pancreatitis is the most common and feared complication of ERCP,
associated with substantial morbidity and occasional mortality.
• Asymptomatic hyperamylasemia occurs after 35% to 70% of ERCPs.
• Clinical acute pancreatitis occurs in 5% of diagnostic ERCPs.
• 7% of therapeutic ERCPs, and up to 25% in those with suspected SOD or
in those with a history of post-ERCP pancreatitis.

23. Diabetes Mellitus
• The diabetic population is also at greater risk for developing severe acute
pancreatitis because they often have many of the known risk factors for
developing severe disease, such as obesity and underlying comorbidities.

24. SOD
• SOD is also a controversial cause of acute pancreatitis.
• Investigators who study patients with recurrent acute pancreatitis report that
SOD (usually defined as a basal pancreatic sphincter pressure > 40 mm Hg) is
the most common abnormality discovered, occurring in approximately 35%
to 40% of patients.

25. Pancreas Divisum
• Pancreas divisum is the most common congenital malformation of the pancreas,
occurring in 5% to 10% of the general healthy population.
• The vast majority of whom never develop pancreatitis.
• Two earlier trials had shown that a 100-mg rectal suppository of diclofenac reduces the
incidence of post ERCP pancreatitis
• Typically, 3- to 5-French unflanged pancreatic stents are used in the following post-ERCP
settings: SOD, difficult cannulation, biliary orifice balloon dilation, and precut
sphincterotomy

26. Miscellaneous
• A recent case-control study from Denmark found a 4-fold increase in acute
pancreatitis in patients with Crohn’s and a 1.5-fold increase in patients with UC
• A Swedish case-control study showed that there is a 4-fold increased rate of
acute pancreatitis in heavy smokers compared with nonsmokers.

28. CLINICAL FEATURES
• It is difficult to diagnose acute pancreatitis by history and physical examination,
because clinical features are similar to those of many acute abdominal illnesses.

29. History
• Abdominal pain is present at the onset of most attacks of acute
pancreatitis.
• Pain in pancreatitis usually involves the entire upper abdomen.
However, it may be epigastric, in the right upper quadrant, or,
infrequently, confined to the left side.
• Pain in the lower abdomen may arise from the rapid spread of
pancreatic exudation to the left colon.

30. • Onset of pain is rapid but not as abrupt as that of a perforated viscus. Usually
it is at maximal intensity in 10 to 20 minutes. Occasionally, pain gradually
increases and takes several hours to reach maximum intensity.
• Pain is steady and moderate to very severe.
• There is little pain relief with changing position.
• Frequently, pain is unbearable, steady, and boring.
• Band-like radiation of the pain to the back occurs in half of patients.

31. • Pain that lasts only a few hours and then disappears suggests a disease
other than pancreatitis, such as biliary colic or peptic ulcer.
• Pain is absent in 5% to 10% of attacks, and a painless presentation may be a
feature of serious fatal disease.
• Ninety percent of affected patients have nausea and vomiting
• Vomiting may be severe, may last for hours, may be accompanied by
retching, and may not alleviate pain.
• Vomiting may be related to severe pain or to inflammation involving the
posterior gastric wall.

32. Physical Examination
• Physical findings vary with the severity of an attack.
• Patients with mild pancreatitis may not appear acutely ill, Abdominal tenderness
may be mild, and abdominal guarding absent.
• In severe pancreatitis, patients look severely ill and often have abdominal
distention, especially epigastric, which is due to gastric, small bowel, or colonic
ileus.
• Almost all patients are tender in the upper abdomen, which may be elicited by
gently shaking the abdomen or by gentle percussion.
• Guarding is more marked in the upper abdomen

33. • Abdominal findings may include ecchymosis in 1 or both flanks (Grey
Turner’s sign or about the
periumbilical area (Cullen’s sign), owing to extravasation of
hemorrhagic pancreatic exudate to these areas.
• These signs occur in less than 1% of cases and are associated with a
poor prognosis

34. LABORATORY DIAGNOSIS
Pancreatic Enzymes
• In general, the diagnosis of acute pancreatitis relies on at least
a 3-fold elevation of serum amylase or lipase in the blood.
Serum Amylase Level
In healthy persons, the pancreas accounts for 40% to 45% of
serum amylase activity, the salivary glands accounting for the
rest.

35. • Simple analytic techniques can separate pancreatic and salivary amylases.
Because pancreatic diseases increase serum pancreatic (P) isoamylase,
measurement of P-isoamylase can improve diagnostic accuracy.
• However, this test is rarely used

36. • It rises within 6 to 12 hours of onset and is cleared fairly rapidly from the blood
(half-life, 10 hours).
• Probably less than 25% of serum amylase is removed by the kidneys.
• The serum amylase is usually increased on the first day of symptoms, and it
remains elevated for 3 to 5 days in uncomplicated attacks

37. • Chronic elevations of serum amylase (without amylasuria) occur in macroamylasemia.
• In this condition, normal serum amylase is bound to an immunoglobulin or abnormal serum
protein to form a complex that is too large to be filtered by renal glomeruli and thus has a
prolonged serum half-life.
• Macroamylasemia may complicate the diagnosis of pancreatic disease, but it has no other
clinical consequence.
• The urinary amylase-to-creatinine clearance ratio (ACCR) increases from approximately 3% to
approximately 10% in acute pancreatitis.

38. Serum Lipase Level
• The sensitivity of serum lipase for the diagnosis of acute pancreatitis is similar to
that of serum amylase and is above 85%.
• Lipase may have greater specificity for pancreatitis than amylase.
• Serum lipase is normal when serum amylase is elevated, as in salivary gland
dysfunction, tumors, gynecologic conditions, and macroamylasemia.
• Serum lipase always is elevated on the first day of illness and remains elevated
longer than does the serum amylase, providing a higher sensitivity.

39. Standard Blood Tests
• The WBC count frequently is elevated, often markedly so in severe pancreatitis, and is not
related to a presence of infection.
• The blood glucose also may be high and associated with
high levels of serum glucagon.
• Serum AST, ALT, alkaline phosphatase, and bilirubin also may increase, particularly in
gallstone pancreatitis
Decreased serum calcium is not from saponification.
• The erythrocyte mean corpuscular volume (MCV) has been shown to help differentiate
alcoholic from nonalcoholic acute pancreatitis.
• Alcoholic patients tend to have a higher MCV due to the toxic effects of alcohol
on erythrocyte formation in the bone marrow.

40. Chest Radiography
• Abnormalities visible on the chest X-ray occur in 30% of patients with acute
pancreatitis.
• including elevation of a hemi diaphragm, pleural effusion(s), basal or plate-like
atelectasis secondary to limited respiratory excursion, and pulmonary infiltrates.
• Pleural effusions may be bilateral or confined to the left side; rarely they are only on
the right side.
• Patients with acute pancreatitis found to have a pleural effusion and or pulmonary
infiltrate on admission are more likely to have severe disease.
• During the first 7 to 10 days, there also may be signs of acute respiratory distress
syndrome(ARDS) or heart failure(HF).
• Pericardial effusion is rare.

41. Abdominal US
• Abdominal US is used during the first 24 hours of hospitalization to search for
gallstones, dilation of the bile duct due to choledocholithiasis, and ascites.
• Ascites is common in patients with moderate to severe acute pancreatitis as
protein-rich fluid extravasates from the intravascular compartment to the
peritoneal cavity.
• If the pancreas is visualized (bowel gas obscures the pancreas 25% to 35% of the
time), it is usually diffusely enlarged and hypoechoic.

42. DIAGNOSTIC IMAGING
• Abdominal Plain Film Findings on a plain radiograph range from no
abnormalities in mild disease to localized ileus of a segment of small.

43. EUS and ERCP
• Usually EUS is not helpful early in acute pancreatitis.
• Imaging of the pancreas during an attack of acute pancreatitis and weeks following an
episode reveal signals that are not normal (typically hypo echoic) and indistinguishable
from chronic pancreatitis and malignancy.
• However, after a month, especially in patients with idiopathic interstitial pancreatitis,
EUS may help determine the presence of small tumors, pancreas divisum, and bile duct
stones.
• EUS is equivalent to MRCP and ERCP but far more sensitive than either abdominal US
or CT in detecting common duct stones

44. CT-Scan
o CT is the most important imaging test for the diagnosis of acute pancreatitis and its intra-abdominal
complications.
The 3 main indications for a CT in acute pancreatitis are to:
(1) exclude other serious intra-abdominal conditions (e.g., mesenteric infarction or a perforated ulcer)
(2) stage the severity of acute pancreatitis.
(3) determine whether complications of pancreatitis are present (e.g., involvement of the GI tract or
nearby blood vessels and organs, including liver, spleen, and kidney).

47. MRI
• MRI is better than CT, but equal to EUS and ERCP in detecting choledocholithiasis.
• MRI is less accessible and more expensive than CT.
• This has been shown to be particularly useful in the evaluation of patients with
idiopathic pancreatitis and recurrent pancreatitis.

48. PREDICTORS OF DISEASE SEVERITY
• The definition of the severity of acute pancreatitis early in the course of disease
(during the first week) is typically based on clinical rather than anatomic
parameters.

55. Number of criteria Mortality rate
0-2 1%
3-4 16%
5-6 40%
7-8 100%

57. Laboratory Markers
• Because the degree of elevation of serum amylase and lipase does not
distinguish mild from severe pancreatitis, other laboratory tests have been
examined.

58. Blood Urea Nitrogen
• Several prognostic scoring systems, including the ranson criteria and
BISAP, incorporate BUN levels for the prediction of mortality in patients
with acute pancreatitis.
• Hemoconcentration, as described earlier, has been shown to be an
accurate predictor of necrosis and organ failure.

59. Hematocrit
• A high hematocrit on admission, or 1 that fails to decrease after 24 hours of
rehydration, is thought to be a sign of hemoconcentration from retroperitoneal
fluid loss and thus is a marker of severe disease.
• One study showed that a hematocrit greater than 44% had a sensitivity of 72%
on admission and of 94% after 24 hours in detecting organ failure.
• most investigators have found hematocrit to be important in the management
of patients with acute pancreatitis.
• An elevated hematocrit ( >44%) is a predictor for the development of necrosis.

60. C-Reactive Protein
• CRP, an acute-phase reactant produced by the liver, is used extensively in Europe
as a marker of severe pancreatitis
• CRP is inexpensive to measure and readily available.
• At a cutoff of 21 mg/dL, the sensitivity of CRP in detecting severe disease in
patients with acute pancreatitis is only 60%, but the test is highly specific.

61. Urinary Trypsinogen Activation Peptide
• Urinary TAP may serve as an early predictor of severity in patients with acute
pancreatitis
• Elevated urinary TAP ( >30 nmol/L) correlates with disease severity.
• The test can be applied within 12 hours of admission.

62. Procalcitonin
• This propeptide is another acute-phase reactant that has been shown to
differentiate mild from severe acute pancreatitis within the first 24 hours after
symptom onset.

63. Chest Radiography
• A pleural effusion documented within 72 hours of admission by chest
radiography (or CT) correlates with severe disease

65. Algorithm for the management of acute pancreatitis at various stages in its course

68. Fluid replacement is to maintain urine out put >0.5cc-1/kg per hour

70. Cardiovascular Care
• Cardiac complications of severe acute pancreatitis include congestive heart
failure, myocardial infarction, cardiac dysrhythmia, and cardiogenic shock.
• If hypotension persists even with appropriate fluid resuscitation.
• IV dopamine may help maintain the systemic blood pressure.
• Dopamine does not impair the microcirculation of the pancreas as do other
vasoconstrictor

71. Respiratory Care
• Hypoxemia (oxygen saturation < 90%) requires supplemental
oxygen, ideally by nasal prongs or by face mask if needed.
• current guidelines recommend the initial routine use of nasal cannula oxygen in all
patients with acute pancreatitis.

72. Antibiotics
• In the absence of infection, antibiotics are not indicated in mild pancreatitis
• However, antibiotics would be appropriate in pancreatic sepsis (e.g. Infected necrosis and, less
often, abscess) and non pancreatic sepsis (e.g., line sepsis, urosepsis,or pneumonia).
• Imipenem,meropenem, floroquinolones (ciprofloxacin, ofloxacin,), and metronidazole
emerged as the drugs that achieved the highest inhibitory concentrations in pancreatic tissue.

74. Nutrition
• In patients with mild disease, the timing of initiating oral intake is unclear.
• Two reports in patients with mild disease suggested that early refeeding
improved outcome and allowed early discharge.
• Patients with severe acute pancreatitis, especially with pancreatic necrosis, may
need 4 to 6 weeks of artificial nutritional support.

86. Pancreatic encephalopathy
• Consists of a variety of central nervous system symptoms occurring in patients
with acute pancreatitis, including agitation, hallucinations, confusion,
disorientation, and coma

87. Purtsher’s retinopathy
• (discrete flame-shaped hemorrhages with cotton wool spots) can cause sudden
blindness.
• It is thought to be due to micro embolization in the choroidal and retinal arteries.

88. Case presentation
A 50- years- old female patient were admitted to the mehraban hospital at
emergency room on Thursday with history of sever and boring acute epigastric
pain with nausea and vomiting, the pain is radiated to the both flanks and back,
worsening by lying supine and better by sitting and leaning for ward , the patient
medical history included obesity and history of CCX from 5 years ago.

91. Name: Simin khanum ‫محترمه‬
:
‫خانم‬ ‫سیمین‬
Father.Name: Mh-Omar ‫عمر‬ ‫محمد‬ ‫پدر‬ ‫نام‬
:
Code number: 1793
Age: 45Y
SEX: F Refered by Dr. :‫محمدی‬ ‫صاحب‬ ‫متخصص‬
Date: 1399/05/31 Time Reporte:
Pancaratit Profile
Test Result Normal Range Unit
Amylase 426 <100 U/L
Lipase 354 <60 U/L

92. Name: Simin khanum ‫محترمه‬
:
‫خانم‬ ‫سیمین‬
Father.Name: Mh-Omar ‫پدر‬ ‫نام‬
:
‫عمر‬ ‫محمد‬
Code number: 1809
Age: .
SEX: F Refered by Dr. :‫محمدی‬ ‫صاحب‬ ‫متخصص‬
Date: 1399/05/31 Time Reporte:
Biochemistry
Test Result Normal Range Unit
Triglycerides 102 40-200 mg/dl
Total Cholestrol 207 130-200 mg/dl
L.D.L 145 Up to 150 mg/dl
H.D.L 41 30---70 mg/dl

93. Urea 28 child.11-36 Adult. 18-45 mg/dl
Creatinin 0.67 f:0.3-1-2 M:0.4-1.4 mg/d
BUN 13 <25 mg/d
Bilirubin Total 7.13 <1.2 mg/d
Bilirubin Direct 3.17 <0.4 mg/d
Bilirubin Indirect 3.96 <0.8 mg/dl
SGOT (ASAT) 396 M. 37 F: 31 U/L
SGPT(ALAT) 489 M. upto: 45 F: upto 35 U/L
Alk.Phosphotase 670 F. 64 -- 306 .M. 80- 306 Child:180-1200U/L
L.D.H 1266 18--65 Year <480 : >65 Year <530 U/L

94. Serology
Test Result Normal Range Unit
H.B.s Ag Negative(-) Negative
H.C.V Ab Negative(-) Negative
H.I.V Negative(-) Negative
HAV IGM Negative(-)
Hbe Ag Negative(-)

95. Name:Simin khanum f/n Mh-Omar sex.F. age:y ID:1809
Date: 1399/5/31 Time Reporte:
Refered By: Dr . Mohamamdi
ELECTROLYTES
Test Result Units Normal Range
Sudium..Na 134 mmol/L: 135-145mmol/L
Potassium. K 6.1 mmol/L: 3.5- 5.5 mmol/L
CI……….. 105 mmol/L: 98 – 108 mmol/L
iCa ...... 1.09 mmol/L (1.15-1.33mmol/L)
Calcium ...... 8.87 mg/dl (8.6-10.3mg/dl)
Magnesium 1.98 mg/dl 1.9-2.6
ph………….. 7.62 7.2-7.6
phosphorus. 6.61 mg/dl 2.6-4.5

97. Scoring the disease
• BISAP SCORE =0
• SIRS CORE =0
• APACHE 2=not measured
• RANSON SCORE=2
• MODIFIED GLASGOW score=1

99. Name: Semen ‫محترمه‬
:
‫سیمین‬
Father.Name: Mh.Omar
‫پدر‬ ‫نام‬
:
‫محمدعمر‬
Code number: 1862
Age: 55y
SEX: f Refered by Dr. :‫محمدی‬ ‫صاحب‬ ‫متخصص‬
Date: 1399/06/01 Time Reporte:
Pancaratit Profile
Test Result Normal Range Unit
Amylase 69 <100 U/L
Lipase 71 <60 U/L

101. Name: Semin ‫محترمه‬
:
‫سیمین‬
Father.Name: Mh.Omar ‫پدر‬ ‫نام‬
:
‫محمدعمر‬
Code number: 1923
Age: 48y
SEX: f Refered by Dr. :‫مسعود‬ ‫صاحب‬ ‫متخصص‬
Date: 1399/06/02 Time Reporte:10:49 AM
Biochemistry
Test Result Normal Range Unit
RBS 70 70-170 mg/dl
BUN 12 <25 mg/d
Bilirubin Total 2.30 H <1.2 mg/d
Bilirubin Direct 0.96 <0.4 mg/d
Bilirubin Indirect 1.34 H <0.8 mg/dl
SGOT (ASAT) 136 H M. 37 F: 31 U/L
SGPT(ALAT) 327 H M. upto: 45 F: upto 35 U/L
Alk.Phosphotase 520 H F. 64 -- 306 .M. 80- 306 Child:180-1200U/L
L.D.H 545 H 18--65 Year <480 : >65 Year <530 U/L

102. Thank You