Good topic on PUD

1. ACUTE PANCREATITIS
 Presented by
 Dr E.P Amaning

2. PATHOPHYSIOLOGY
 Occurs when homeostasis is disrupted
 Acinar cell injury pancreastasis (intra-cellular
glutathione, ATP & disruption of microtubule,
microfilaments) trypsinogen activation
production of molecular fragments which serve as
chemo-attractants for the inflammatory cascade
(activated neutrophils, superoxides, proteolytic
enzymes-cathepsins B, D, and C, collagenase and
elastase.)
 release of cytokines( TNF-alpha,IL-6, IL-8 )
mediating local and systemic inflammatory
responses.

3. INTRODUCTION
 Function of the pancreas is to make food-
digesting enzymes.
 Makes 0.1% of body wgt, has 13 times
production capacity of liver & RES.
 Several mechanisms to prevent auto-digestion:
inactive protein forms (proenzymes), later
posttranslational modification of digestive
proteins, package into subcellular
compartment (lysosomes & zymogen
granules). Low Ca++ and acidic pH prevents
activation within the zymogen granules.
 Intracellular enzyme activation and pancreatic
auto-digestion  acute pancreatitis.

4. EPIDEMIOLOGY
 Freq: in the US 183,000 reported cases in 1998
 Overall mortality 10-15%, in severe disease 30%
 Major cause of death in first week: multi-organ
system failure, later weeks: infections
 Race: more common in blacks
 Sex: males >>females; males related to alcohol,
females to biliary tract disease.
 Idiopathic pancreatitis has no sex predilection.

5. Age
Causes Median age
(yrs)
Vasculitis related 36
Alcohol related 39
Biliary tract 69
trauma 66
Drug induced 42
ERCP 58
AIDS 31

6. HISTORY
 Cardinal symptom: abdominal pain (dull, boring & steady) in
epigastric region / left or right side depending on which side
of pancreas is involved, radiates to the back.
 duration: > one day
 Aggravated by: eating or lying supine,
 Alleviated by: fasting or lying on left side with hips and knees
flexed.
 Ass. Symptoms: anorexia, nausea, vomiting, diarrhoea.

7. Physical examination
 Fever and tachycardia
 Abdominal tenderness, muscular guarding,
distension, hypoactive bowel sounds.
 Dyspnoea ( irritation of diaphragm or
respiratory distress syndrome)
 Hemodynamic instability and hematemesis or
melaena stools
 Uncommon findings (severe necrotising
pancreatitis): Cullen’s sign, Grey-Turner’s sign,
erythematous skin nodules, Purtscher
retinopathy (ischemic injury to the retina
caused by activation of complement and
agglutination of blood cells within retinal
vessel).

8. CAUSES
Biliary tract disease
(38%)
Due to gallstones lodging in
the sphincter of Oddi. Risk is
inversely proportional to the
size of the stone.
Alcohol (35%) Due to alcohol abuse
Post ERCP (4%)
Abdominal trauma
(1.5%)
Often in penetrating injuries,
or crush injuries
Toxins (<1%) Organophosphates, Tityus
trinitatis scorpion.
Postoperative 1% Unclear mechanism

9. CAUSES
Drugs ( 1.4%) Azathioprine, sulfonamides,
sulindac, corticosteroids etc
Infection (<1%) EBV, mumps, salmonella,
M.tuberculosis etc.
Hereditary Autosomal dominant.
hypercalcemia
Dev anomalies Annular pancreas, divisum
pancreas.
tumors Pancreatic ductal ca ampullary
ca cholangiocarcinoma,
hypertriglyceridemia

10. Differentials
 Abdominal trauma
(blunt or penetrating)
 Acute abdomen
 Biliary colic
 Cholangitis
 Cholecystitis
 Diverticulitis
 Duodenal ulcers
 Myocardial infarction
 Emphysema
 Emphysematous
cholecystitis
 Acute gastritis
 Hyperamylasaemia
 Intestinal perforation
 Intra- abd. sepsis
 Mesenteric vascular
thrombosis
 Omental torsion

11. WORK UP- lab studies
 amylase and lipase: (typically elevated though may
only indicate pancreastasis). Elevations also occur ff
intestinal obstruction, mesenteric ischemia, tubo-
ovarian abscess, renal insufficiency,
macroamylasemia, parotitis.
 Return to baseline in a few days, lipase has a longer
half life.
 The levels do not indicate severity of disease.

12. WORK-UP
 Liver assoc. enzymes: ALP, total bilirubin, AST, ALT
to rule out gallstone etiology. ALT > 150U/L suggests
gallstone pancreatitis.
 Calcium, cholesterol, triglycerides: to search for
the cause or complications (hypocalcaemia)
 Serum electrolytes, BUN, creatinine, glucose
 FBC: admission Ht >47% may predict severe
necrotizing pancreatitis. Leukocytosis implies
infection or inflammation

13. WORK-UP
 C- reactive protein (non-specific ): to indicate
prognosis, values >10mg% indicates severe
pancreatitis.
 Arterial blood gases

14. IMAGING STUDIES
 Abdominal radiography: has a limited role; can be
used in detecting a perforated viscus; colon cut-off
sign,sentinel loop sign or an ileus, may show
calcifications in chronic cases.
 Abdominal US: most useful initial test in etiologic
diagnosis; technique of choice in detecting gall
stones. Sensitivity  70-80% in acute cases. It
cannot determine severity of the disease.

15. IMAGING STUDIES
 Abdominal CT scanning: it is indicated; useful in
assessing complications. Scans are unneeded in the
first 72hrs after onset of symptoms except
diagnosis is uncertain.
 It provides prognostic information using the
Balthazar scale( see below ).
 Dynamic spiral CT scan: presence and extent of
pancreatic necrosis (focal or diffuse areas of
unenhanced parenchyma)

16. Balthazar grading scale
A normal
B enlargement
C Peri-pancreatic inflammation
D Single fluid collection
E Multiple fluid collection 50% chance of
developing an
infection; 15%
chance of dying

17. IMAGING STUDIES
 MRCP: has a role in diagnosis of biliary and
pancreatic duct obstruction. Sensitivity lower than
ERCP. It is safer, non-invasive, fast and provides
images useful in guiding clinical care decisions
 Endoscopic US: useful in detecting microlithiasis
and peri- ampullary lesions. Secretin stimulated
EUS useful in recurrent idiopathic pancreatitis.

18. PROCEDURES
 ERCP: used to evaluate the biliary and peri-ductal
system.
 Safe in acute gallstone pancreatitis and assoc
cholangitis.
 In detecting uncommon causes viz peri-ampullary
duodenal diverticulum, pancreatic duct strictures
pancreas divisum etc.
 ERCP + sphincter of Oddi manometry reveals SOD
as cause of recurrent pancreatitis

19. PROCEDURES
 CT-guided needle aspiration: to
differentiate btw infected & sterile
necrosis in severe necrotizing
pancreatitis. Specimen should be sent
promptly to the lab. Surgical
debridement if Gram stain shows
bacteria or fungi.

20. HISTOLOGIC FINDINGS
 Mild cases: interstitial edema + inflammatory
infiltrate without hemorrhage or necrosis.
 Severe cases: extensive inflammation and necrosis
+ gland dysfunction & multi-organ system failure.
 Very severe cases: arterial thrombosis results in
pan-lobular infarction hemorrhagic, gangrenous
and necrotic mass.

21. STAGING
 Currently no recognised standard criteria
 Ranson’s: valid only at 48hrs after onset, threshold
of parameters depends on cause (alcohol or
gallstone). Sensitivity is 73%, specificity 77%.
 Acute physiology and chronic health evaluation
(APACHE): very cumbersome for clinical use.
Sensitivity 77%, specificity 84%.
 Peritoneal lavage: high specificity 93%, sensitivity
54%
 C-reactive protein: values > 6 at 24hrs or 7 at
48hrs indicate a severe disease. Sensitivity 73%,
specificity 71%.

22. TREATMENT
 Medical management: in mild cases NPO, IVF,
analgesics. Antibiotics are not indicated.
 Gallstones: laparoscopic cholecystectomy.
 Severe cases: require intensive care, goal is to
provide aggressive supportive care,  inflammation,
limit infection, identify and treat complications.
 Fluids, antibiotics (imipenem/ cilastatin or
metronidazole +levofloxacin), early ERCP +
sphincterotomy if indicated, nutritional
supplementation.

23. TREATMENT
 Emerging treatment: lexipafant ( a platelet-
activating factor antagonist) has shown no benefit
 Clinical vigilance: in later weeks after presentation
signs of intra-abdominal infection, pseudocyst,
hemorrhage, colon perforation, obstruction or
fistulation & multi-organ system failure should be
sought.
 Signs of infection is an indication for CT-guided
needle aspiration.

24. SURGICAL CARE
 Indicated when an anatomic complication
amenable to mechanical solution is present.
 Pancreatic duct disruption:  retroperitoneal
fluid on CT scan or sudden development of
hypocalcaemia is suggestive. Managed by
ultrasound guided drainage tube insertion.
Endoscopic retrograde pancreatography
confirms diagnosis and is also therapeutic.
Transpapillary stent placement or a 6F
nasopancreatic tube attached to an external
suction device is helpful.

25.  Refractory cases: distal pancreatectomy if in tail of
pancreas; Whipple’s procedure if in the head of
pancreas.

26. PSEUDOCYSTS
 Defined as peripancreatic fluid collections persisting
for more than 4 weeks. Intervention needed only if
cyst is larger than 7cm or rapidly expanding.
Treatment includes:
 Percutaneous aspiration.
 Endoscopic techniques: transpapillary drainage (main
duct communicates with the pseudocyst cavity).
Transmural enterocystostomy in non-communicating
cases.

27. INFECTED PANCREATIC
NECROSIS
 Surgery indicated in large areas of necrosis and
positive Gram’s stain following aspiration.
 Aggressive surgical debridement and drainage is
necessary.
 Percutaneous catheter drainage and antibiotics in
pancreatic abscess formation.

28. CONSULTATION
 Treat the underlying cause.
 Alcohol-induced: need to address the underlying
addiction, consult to a counsellor
 Hyper-triglyceridemic or hypercalcemic induced:
consult to endocrinologist
 Gall stones or microlithiasis: consult for
cholecystectomy.
 Diet: mild cases (5% dextrose); severe cases
(parenteral nutrition to include fat emulsions to
prevent essential fatty acid deficiency). Naso-
jejunal tube for enteral nutrition after patient is
stable.

29. CONSULTATION
 Begin oral feeding once abdominal pain has
subsided and the patient has regained appetite.
Diet should be low in fat and protein.

30. SUMMARY
 Acute pancreatitis is a life-threatening, multi-
organ failure-disposing acute inflammation of the
pancreas, resulting from intracellular activation of
normally inactive pro-enzymes,followed by
pancreatic autodigestion.
 It is recognised by the presence of :
 Sudden,severe abdominal pain,associated with
anorexia,nausea,and vomiting.

31.  Biliary tract disease(38%) and chronic alcohol
abuse(35%) are the major causes.
Trauma(1.5%),drugs(1.4%),infection,especially
viral(1%),hereditary factors(1%),developmental
anomalies of the
pancreas(1%),hypertriglyceridemia(1%),tumor(1%)
,postoperative conditions(1%),and idiopathic
factors(10%) are the other causes.

32.  Biochemical investigations such as serum
amylase and serum lipase as well as CRP are
helpful in diagnosis.
Imaging studies such as abdominal ultrasound,
abdominal CTscan,ERCP and MRCP are needed
for confirmation or when in doubt.

33.  Staging is by means of prognostic
criteria(Ranson,Imrie,Glasgow,APACHE and APACHE
II),C-Reactive Protein measurement.Others Trypsin
activation peptide,Polymorphonuclear elastase,IL-
6,PhospholipaseA2 are also available,but not widely
used(expensive)

34. PROGNOSTIC FACTORS IN
ACUTE PANCREATITIS
 Background
 Early differentiation between mild and severe
pancreatitis is of crucial prognostic and
therapeutic importance.
 Serum markers that help to do this are:
 1.Polymorphonuclear cell elastase (PMNE)
 2.C-Reactive Protein (CRP)

35.  Together PMNE and CRP are able to predict development
of necrosis 80% of the time. PMNE peaks within 1-2
days, while CRP peaks 3-4 days later and remains
elevated as long as there is ongoing inflammation.
 3.Serum Phospholipase A2 (PLA2) correlates with the
extent of necrosis and predicts the likelihood of
pulmonary complications.The assay is however difficult
and expensive,therefore reserved for research purposes
only.

36.  4.Trypsinogen Activation Peptides ( TAP ): These are
small peptides cleaved from trypsinogen by
enterokinase in the gut lumen and therefore absent
from the blood normally. In acute pancreatitis, trypsin
activation occurs extraluminally ( in the
retroperitonum ), releasing TAP into the circulation
from where they are excreted through the kidney.
Therefore TAP are a specific indicator of the extent of
extraperitoneal trypsinogen activation and the most
useful biochemical marker for assessing the severity
of acute pancreatitis. Its sensitivity is 80% and
specificity 90%. In mild pancreatitis, there is little or
no TAP.

37. CLINICAL SCORING SYSTEM
 Background
 Most institutions do not have the capacity to assay
the serum markers that help distinguish between
mild and severe acute pancreatitis. Clinical scoring
systems are therefore widely used.
 Most popular is the Ransons system consisting of 11
easily obtainable clinical parameters at admission and
48hours later.Presence of up to 3 signs suggests
favorable outcome,4 or more signs portend a
complicated course.

38. RANSONS SIGNS OF SEVERE
PANCREATITIS
 At admission:
 Age > 55years
 WBC > 16,000
 Blood glucose > 200mg/dl
 Serum lactate dehydrogenase > 300 IU/L
 Serum glutamic- oxaloacetic transaminase >250U

39.  48hr after admission:
 Hematocrit fall> 10%
 Blood Urea Nitrogen rise > 5mg/dl
 Serum Calcium < 8mg/dl
 Arterial PO2 < 60mmHg
 Estimated fluid sequestration > 6L
 Base deficit > 4mEq/L.