a basic overview of the diagnosis and management of acute pancreatitis.

1. Acute Pancreatitis
EYOB HABTAMU, (MD/009/2015)

2. Outline
Introduction
 The normal pancrease
 Definition and pathogenesis of acute pancreatitis
 Causes of acute pancreatitis
Clinical presentation
 History
 Physical examination
 Laboratory examination findings
Assement of severity & hospital triage
Management
Complications

3. Introduction
The pancrease is an organ in the digestive system and
endocrine system.
◦ Endocrine hormones: Insulin, glucagon, and pancreatic
polypeptide
◦ Digestive secretions: Trypsinogen, Chymotrypsinogen,
Carboxypeptidase, elastases, Pancreatic lipase, Pancreatic
amylase
◦ Exocrine secretions: Secretin, Cholecystokinin (CCK), Gastric
inhibitory peptide (GIP), Somatostatin

4. Auto protection of the pancrease
Protection of the pancreatic tissue is facilitated by:
• The packaging of pancreatic proteases in precursor (proenzyme) form
• Intracellular calcium homeostasis
• Acid-base balance
• The synthesis of protective protease inhibitors

5. Acute pancreatitis
• Acute pancreatitis is the sudden onset of reversible inflammation of the pancrease,
•It is estimated to affect between 4.5 and 35 in every 100,000 individuals per year.
• Acute pancreatitis can vary from mild (mortality rate less than 1%; typically resolves in several days)
to severe (mortality rate up to 30%).
• Mortality rates are highest in patients with:
•hemorrhagic pancreatitis,
•multiorgan dysfunction or failure,
•necrotizing pancreatitis.
•The incidence of acute pancreatitis increases with age. Onset in the first decade suggests a hereditary
cause, infection, or trauma.

6. Pathogenesis
The pathogenesis of this disorder is not fully understood, but Acute pancreatitis occurs
when there is abnormal activation of digestive enzymes within the pancrease.
6
Inappropriate activation of inactive enzyme precursors called zymogens
(Trypsinogen)
Trypsin leads to further activation of other digestive enzymes
Inflammation, edema, vascular injury, and cellular death.
Endotoxins, exotoxins, viral infections, ischemia, oxidative
stress, lysosomal calcium, and direct trauma

7. Etiology
•

10. Etiology (Gall stones)
•Gallstones account for 35 to 40 % of cases, but only 3 to 7% of patients with gallstones develop
pancreatitis.
•Mechanism by which the passage of gallstones induces pancreatitis is unknown, but suggested
mechanisms include:
 Reflux of bile into the pancreatic duct due to transient obstruction of the ampulla during
passage of gallstones
 Obstruction at the ampulla secondary to stone or edema resulting from the passage of a
stone
•An elevated serum ALT is the most clinically useful parameter in predicting a gallstone etiology in
patients with acute pancreatitis.

11. Etiology (Biliary sludge and microlithiasis)
•Most patients with biliary sludge are asymptomatic.
• Biliary sludge is found in 20-40% of patients with acute pancreatitis with no obvious cause.
•In the absence of any other etiology, biliary sludge should be suspected in patients with acute
pancreatitis with a transient elevation in liver tests.
•Sludge is found in patients with stasis, which may be secondary to:
•Prolonged fast
•Total parenteral nutrition
•Ceftriaxone use

12. Etiology (Alcohol)
•Responsible for approximately 30% of cases of acute pancreatitis in the US.
•Exact mechanism is unknown, but suggested ideas include:
increased synthesis of enzymes that are thought to be responsible for acute pancreatitis
over-sensitization of acini to cholecystokinin
abnormal sphincter of Oddi motility
small duct obstruction by protein plug formation
direct toxic and metabolic effects,
•The diagnosis should not be entertained unless a person has a history of over 5 years of heavy alcohol
consumption.

13. Etiology (Drugs)
•Pancreatitis due to medications is rare (0.3 to 1.4%)
•Suggested mechanisms include:
 immunologic reactions (eg, 6-mercaptopurine, aminosalicylates, sulfonamides),
 direct toxic effect (eg, diuretics, sulfonamides),
 accumulation of a toxic metabolite (valproic acid, didanosine, pentamidine, tetracycline),
 ischemia (diuretics, azathioprine)
 intravascular thrombosis (estrogen),
 increased viscosity of pancreatic juice (diuretics and steroids).
•The prognosis of drug-induced pancreatitis is generally excellent and mortality is low.

14. Determining the etiology of acute
pancreatitis
•The etiology of acute pancreatitis can be established in at least 75 % of patients.
•History- focus on previous symptoms or documentation of gallstones, alcohol use, history of
hypertriglyceridemia or hypercalcemia, family history of pancreatic disease, drug history, history
of trauma, and the presence of concomitant autoimmune diseases.
•Labs- on admission, all patients should have a serum amylase or lipase, triglyceride level,
calcium level, and liver biochemistries.
•Imaging- abdominal ultrasound should be obtained on admission in all patients with acute
pancreatitis to evaluate for cholelithiasis or choledocholithiasis. Repeat after recovery if clinical
suspicion for gallstones remains.
-
* Extensive or invasive evaluation is usually not recommended in those with a single episode of
pancreatitis who are younger than 40.

15. Clinical presentation

16. Symptoms
•The disease varies in severity and the diagnosis is often missed at the extreme ends of the spectrum.
•Almost all patients with acute pancreatitis have acute upper abdominal pain at the onset.
Location: mid-epigastrium, right upper quadrant, diffuse (infrequently confined to the left side)
Character: steady, gnawing
Radiation: may radiate to the back (50% of cases), or throughout the abdomen and into the chest
Severity : usually very sever (mild or absent in some cases)
Aggravating and alleviating factors: Initially, the pain worsens after eating or drinking, especially fatty foods,
and then typically becomes constant over time. Leaning forward may relieve the pain.
Associated symptoms: Nausea, vomiting, anorexia, frequent hiccups.
Onset: rapid, reaching maximum intensity in 10-20 min.
* The intensity and location of the pain do not correlate with severity.

17. Physical signs
•The physical examination findings may be normal or reveal fever, hypotension, tachycardia,
tachypnea, or diaphoresis.
•Abdominal examination typically reveals
Notable tenderness to palpation,
Guarding,
Signs of peritoneal irritation,
Distension, or rigidity,
Decreased bowel sounds,
Jaundice may be present.
• Basilar rales, and signs of atelectasis, & pleural effusion may be present in 10-20%.
•In severe disease, patients may present with altered mental status.

18. Physical signs (less common)
Grey-Turner's sign: hemorrhagic discoloration of the flanks
Cullen's sign: hemorrhagic discoloration of the umbilicus
Grunewald 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
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)
Pandiaraja's sign: ecchymosis of right axilla

19. Laboratory examination
•Overall, history and physical examination have moderate accuracy, especially when findings are
abnormal.
•Laboratory testing can assist in diagnosis, classify the severity of disease, and predict outcomes.
• Serum amylase and lipase values threefold or more above normal virtually clinch the diagnosis if gut
perforation, ischemia, and infarction are excluded.
•Other tests that should be ordered at presentation include a
complete blood count;
comprehensive metabolic panel including renal and hepatic function
 urinalysis;
lipase, calcium, LDH, and triglyceride levels
If alcohol abuse is a factor, magnesium and phosphorous levels should be assessed.

20. Laboratory examination(2)
•In acute pancreatitis, the serum amylase and lipase are usually elevated within 24 h of onset and
remain so for 3–7 days.
•Approximately 85% of patients with acute pancreatitis have a threefold or greater elevated
serum lipase and amylase levels.
•The values may be normal if:
(1) there is a delay (of 2–5 days) before blood samples are obtained,
(2) the underlying disorder is chronic pancreatitis rather than acute pancreatitis, or
(3) hypertriglyceridemia is present.
•Lipase is the single best enzyme to measure for the diagnosis of acute pancreatitis.
There is no correlation between the severity of pancreatitis and the degree of serum lipase and
amylase elevations.

21. Causes of hyperamylasemia

22. Laboratory examination(3)
•Leukocytosis (15,000–20,000 leukocytes/μL) occurs frequently in acute pancreatitis.
•Hemoconcentration may be the harbinger of more severe disease (i.e., pancreatic necrosis), whereas azotemia is
a significant risk factor for mortality.
•Hyperglycemia is common and is due to multiple factors, including decreased insulin release, increased glucagon
release, and an increased adrenal glucocorticoids and catecholamines.
•Hypocalcemia occurs in ~25% of patients, and its pathogenesis is incompletely understood.
•Hyperbilirubinemia (serum bilirubin>4.0 mg/dL) occurs in ~10% of patients.
•Hypertriglyceridemia occurs in 5–10% of patients, and serum amylase levels in these individuals are often
spuriously normal.
•Hypoxemia (arterial PO2 ≤60 mmHg) in 5-10% , may herald the onset of ARDS.
•Electrocardiogram is occasionally abnormal in acute pancreatitis with ST-segment and T-wave abnormalities
simulating myocardial infarction.

23. Imaging findings
•Abdominal ultrasound is recommended in the emergency ward as the initial diagnostic imaging
modality and is most useful to evaluate for gallstone disease and the pancreatic head.
•Contrast-enhanced CT (CECT) and / or MRI of the pancreas should be reserved for patients in
whom the diagnosis is unclear or who fail to improve clinically within the first 48 – 72 h after
hospital admission or to evaluate complications.

24. Diagnosis
Any severe acute pain in the abdomen or back should suggest the possibility of acute
pancreatitis. The diagnosis is established by two of the following three criteria:
(1) Typical abdominal pain in the epigastrium that may radiate to the back,
(2) Threefold or greater elevation in serum lipase and/or amylase,
(3) Confirmatory findings of acute pancreatitis on cross-sectional abdominal imaging.

25. Differential diagnosis
(1) Perforated viscus, especially peptic ulcer;
(2) Acute cholecystitis (may also increase amylase) and biliary colic;
(3) Acute intestinal obstruction;
(4) Mesenteric vascular occlusion;
(5) Renal colic;
(6) Inferior myocardial infarction;
(7) Dissecting aortic aneurysm;
(8) Connective tissue disorders with vasculitis;
(9) Pneumonia;
(10) Diabetic ketoacidosis.

26. Clinical course
EARLY PHASE (< 2 WEEKS )
- severity is defined by clinical parameters
rather than morphologic findings.
- If SIRS, persists, patients are predisposed to
organ failure.
-Three organ systems should be assessed to
define organ failure: respiratory,
cardiovascular, and renal.
-Persistent organ failure (>48 h) is the most
important clinical finding in regard to severity
of the acute pancreatitis episode.
LATE PHASE (> 2 WEEKS )
- characterized by a protracted course of illness
and may require imaging to evaluate for local
complications.
-The important clinical parameter of severity, as
in the early phase, is persistent organ failure
-These patients may require supportive measures
such as renal dialysis, ventilator support, or need
for supplemental nutrition via the nasojejunal or
parenteral route.
-The radiographic feature of greatest importance
to recognize in this phase is the development of
necrotizing pancreatitis on CT imaging.

27. Primary Assessment
1. Hemodynamic status should be assessed immediately upon presentation and resuscitative
measures begun as needed.
2. Risk assessment should be performed to stratify patients into higher- and lower-risk
categories to assist triage, such as admission to an intensive care setting.
3. Patients with organ failure should be admitted to an intensive care unit or intermediary care
setting whenever possible.

28. Severity of acute pancreatitis
•Mild acute pancreatitis is without local complications or organ failure.
- the disease is self-limited and subsides spontaneously, usually within 3–7 days after treatment
is instituted.
•Moderately severe acute pancreatitis is characterized by transient organ failure (resolves in <48
h) or local or systemic complications in the absence of persistent organ failure.
- These patients may or may not have necrosis, but may develop a local complication such as a
fluid collection that requires a prolonged hospitalization greater than 1 week.
•Severe acute pancreatitis is characterized by persistent organ failure (>48 h). Organ failure can
be single or multiple.
Organ failure is defined as a score of 2 or more for any one of three organ systems (respiratory,
cardiovascular, or renal) using the modified Marshall scoring system.

29. Severity of acute pancreatitis
INTERSTITIAL PANCREATITIS
•Acute inflammation of the pancreatic
parenchyma and peripancreatic tissues, but
without recognizable tissue necrosis
•occurs in 90–95% of admissions for acute
pancreatitis
•is characterized by diffuse gland enlargement,
homogenous contrast enhancement, and mild
inflammatory changes or peripancreatic
stranding.
•Symptoms generally resolve with a week of
hospitalization.
NECROTIZING PANCREATITIS
•Inflammation associated with pancreatic
parenchymal necrosis and/or peripancreatic
necrosis
•occurs in 5–10% of acute pancreatitis
admissions
•Does not evolve until several days of
hospitalization
•is characterized by lack of pancreatic
parenchymal enhancement by intravenous
contrast agent and/or presence of findings of
peripancreatic necrosis.

30. Predicting severe acute pancreatitis
•Clinicians have been largely unable to predict which patients with AP will develop severe
disease.
•The new scoring systems, such as the BISAP, have not shown to be more accurate than the other
scoring systems.
• Also no laboratory test is practically available or consistently accurate to predict severity in
patients with AP.
•CT and/or MRI imaging also cannot reliably determine severity early in the course of AP, as
necrosis usually is not present on admission and may develop after 24– 48 h.
•Thus, in the absence of any available test to determine severity, close examination to assess
early fluid losses, hypovolemic shock, and symptoms suggestive of organ dysfunction is crucial.
* Rather than depending on a scoring system to predict severity of AP, clinicians need to be aware of intrinsic
patient-related risk factors, including laboratory and imaging risk factors, for the development of severe disease.

31. During the first 48 to 72 hours, a rising hematocrit or blood urea nitrogen or creatinine level,
persistent SIRS after adequate fluid resuscitation, or the presence of pancreatic or peripancreatic
necrosis on cross-sectional imaging constitutes evidence of evolving severe pancreatitis.

32. Predicting severe acute pancreatitis
RANSON CRITERIA
◦ At admission:
◦ Age in years > 55 years
◦ WBC count > 16000 cells/mm3
◦ Blood glucose > 11 mmol/L (> 200 mg/dL)
◦ Serum AST > 250 IU/L
◦ Serum LDH > 350 IU/L
◦ Within 48 hours:
◦ Serum calcium < 2.0 mmol/L (< 8.0 mg/dL)
◦ Hematocrit fall > 10%
◦ Oxygen (hypoxemia PaO2 < 60 mmHg)
◦ BUN increased by 1.8 or more mmol/L (5 or more mg/dL) after
IV fluid hydration
◦ Base deficit (negative base excess) > 4 mEq/L
◦ Sequestration of fluids > 6 L
BISAP
– Parameters should be obtained within the
first 24 hours of hospitalization:
 BUN > 25mg/dl.
 Impaired mental status(GCS<15).
 SIRS
 Age > 60 years.
 Pleural effusion on radiography.

33. Management (principles)
• 85-90% of cases of acute pancreatitis are self-limited & subside spontaneously, (usu. 3-7 days
after start of Rx) & do not exhibit organ failure or local complications.
•Administer aggressive fluid resuscitation,
IV fluids( NS or LR ) – initially bloused at 15cc – 20cc/kg, followed by 3ml/kg/hr, to
maintain urine output >0.5cc/kg/hr.
•NPO; IV narcotic analgesics; supplemental Oxygen (2L via nasal cannula).
•Assess for etiology and severity.
•Serial bedside evaluations: every 6-8 hrs.
 Assess: Vital signs, Oxygen saturation , Change in Physical examination.
•Targeted resuscitation strategy – 8-12hrs.
 Measure BUN & Hematocrit.
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34. Management
INITIAL MANAGEMENT
1. Aggressive hydration, (250 – 500 ml per hour of
isotonic crystalloid solution) should be provided to all
patients, unless cardiovascular, renal, or other related
comorbid factors exist. Early aggressive intravenous
hydration is most benefi cial during the first 12 – 24 h,
and may have little benefi t beyond this time period
2. In a patient with severe volume depletion, manifest
as hypotension and tachycardia, more rapid repletion
(bolus) may be needed
3. Lactated Ringer’s solution may be the preferred
isotonic crystalloid replacement fluid
4. Fluid requirements should be reassessed at frequent
intervals within 6 h of admission and for the next 24 –
48 h. Th e goal of aggressive hydration should be to
decrease the BUN
ANTIBIOTICS IN AP
1. Antibiotics should be given for an extrapancreatic
infection, such as cholangitis, catheter-acquired infections,
bacteremia, urinary tract infections, pneumonia
2. Routine use of prophylactic antibiotics in patients with
severe AP is not recommended
. 3. Th e use of antibiotics in patients with sterile necrosis
to prevent the development of infected necrosis is not
recommended
4. Infected necrosis should be considered in patients with
pancreatic or extrapancreatic necrosis who deteriorate or
fail to improve aft er 7 – 10 days of hospitalization. In
these patients, either (i) initial CT-guided fi ne-needle
aspiration (FNA) for Gram stain and culture to guide use of
appropriate antibiotics or (ii) empiric use of antibiotics aft
er obtaining necessary cultures for infectious agents,
without CT FNA, should be given

35. Management (2)
NUTRITION IN AP
1. In mild AP, oral feedings can be started
immediately if there is no nausea and vomiting,
and the abdominal pain has resolved
2. In mild AP, initiation of feeding with a low-fat
solid diet appears as safe as a clear liquid diet
3. In severe AP, enteral nutrition is recommended
to prevent infectious complications. Parenteral
nutrition should be avoided, unless the enteral
route is not available, not tolerated, or not
meeting caloric requirements
4. Nasogastric delivery and nasojejunal delivery
of enteral feeding appear comparable in efficacy
and safety.
SURGERY IN AP
1. In patients with mild AP, found to have gallstones in the
gallbladder, a cholecystectomy should be performed before
discharge to prevent a recurrence of AP
2. In a patient with necrotizing biliary AP, in order to prevent
infection, cholecystectomy is to be deferred until active infl
ammation subsides and fluid collections resolve or stabilize
3. Asymptomatic pseudocysts and pancreatic and/or
extrapancreatic necrosis do not warrant intervention
regardless of size, location, and/or extension
4. In stable patients with infected necrosis, surgical, radiologic,
and /or endoscopic drainage should be delayed preferably for
more than 4 weeks to allow liquefi cation of the contents and
the development of a fibrous wall around the necrosis (walled-
off necrosis)
5. In symptomatic patients with infected necrosis, minimally
invasive methods of necrosectomy are preferred to open
necrosectomy

36. Complications

39. Follow-up care
Evaluate for the development of:
Diabetes
Exocrine insufficiency
Recurrent cholangitis
Development of infected fluid collections.

40. References
•Harrison’s principles of internal medicine 19th edition.
•Up-to-date version 21.6
•Acute pancreatitis; JEFFREY D. QUINLAN, MD, Uniformed Services University of the Health
Sciences, Bethesda, Maryland; Am Fam Physician. 2014;90(9):632-639
•American College of Gastroenterology Guideline: Management of Acute Pancreatitis (2013)
• Acute pancreatitis; Chris E. Forsmark, M.D. et.al N Engl J Med 2016;375:1972-81.

41. Recommended readings
•American College of Gastroenterology Guideline: Management of Acute Pancreatitis (2013 or
later versions)
•Acute pancreatitis; Chris E. Forsmark, M.D. et.al N Engl J Med 2016;375:1972-81.