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Exocrine Function
common bile duct
HEAD BODY
TAIL
ampulla
UNCINATE
pancreatic duct
pancreatic enzymes
Enzyme Secretion
acinus
Enzyme Secretion
Neural
acetylcholine VIP GRP
Hormonal
CCK gastrin
Secretin (hormonal)
H2O bicarbonate
duodenal lumen
trypsinogen
chymotrypsinogen proelastase prophospholipase procarboxypeptidase
trypsin
chymotrypsin elastase phospholipase carboxypeptidase
Exocrine Stimulation
The more proximal the nutrient infusionthe greater the pancreatic stimulation (dog studies) - stomach maximal stimulation - duodenum intermediate stimulation - jejunum minimal / negligible stimulation Elemental formulas tend to cause less stimulation than standard intact formulas - intact protein > oligopeptides > free amino acids Intravenous nutrients (even lipids) do not appear to stimulate the pancreas
Protective Measures
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 trypsin inhibitor is secreted along with the proenzymes to suppress any premature enzyme activation
Acute Pancreatitis
Definition
Usually painful and self-limited Isolated event or a recurring illness Pancreatic function and morphology return
to normal after (or between) attacks
Acute Pancreatitis
Etiology
Other 10%
Idiopathic 10%
Gallstones 45%
EtOH 35%
Acute Pancreatitis
Associated Conditions
Cholelithiasis Ethanol abuse Idiopathic Medications Hyperlipidemia ERCP Trauma
Pancreas divisum Hereditary Hypercalcemia Viral infections - Mumps - Coxsackievirus
Acute Pancreatitis
Causative Drugs
AIDS therapy: didanosine, pentamidine Anti-inflammatory: sulindac, salicylates Antimicrobials: metronidazole, sulfonamides, tetracycline, nitrofurantoin Diuretics: furosemide, thiazides IBD: sulfasalazine, mesalamine Immunosuppressives: azathioprine, 6-mercaptopurine Neuropsychiatric: valproic acid Other: calcium, estrogen, tamoxifen, ACE-I
Pancreas divisum
Hereditary Pancreatitis
Autosomal dominant with 80% phenotypic
penetrance
Acute Pancreatitis
Pathogenesis
acinar cell injury
Acute Pancreatitis
Pathogenesis
premature enzyme activation
Acute Pancreatitis
Pathogenesis
SEVERITY Mild
Acute Pancreatitis
Clinical Presentation
Abdominal pain
- Epigastric - Radiates to the back - Worse in supine position
Acute Pancreatitis
Differential Diagnosis
Acute Pancreatitis
Diagnosis
Symptoms
- Abdominal pain
Laboratory
- Elevated amylase or lipase > 3x upper limits of normal
Radiology
- Abnormal sonogram or CT
Lipase
Parotitis
Biliary stone Intestinal injury Tubo-ovarian disease Renal failure Macroamylasemia
Normal
Normal
Normal
Acute Pancreatitis
Diagnosis
Hyperlipidemia: lipemic serum, Tri>1,000 Hypercalcemia: elevated Ca Trauma: history Medications: history, temporal association
Acute Pancreatitis
Clinical Manifestations
PANCREATIC Mild: edema, inflammation, fat necrosis Severe: phlegmon, necrosis, hemorrhage, infection, abscess, fluid collections Retroperitoneum, perirenal spaces, mesocolon, omentum, and mediastinum Adjacent viscera: ileus, obstruction, perforation SYSTEMIC Cardiovascular: hypotension Pulmonary: pleural effusions, ARDS Renal: acute tubular necrosis Hematologic: disseminated intravascular coag. Metabolic: hypocalcemia, hyperglycemia
PERIPANCREATIC
Acute Pancreatitis
Time Course
ER presentation cytokine release organ failure
12
24
36
48
60
72
84
96
Med intake Family History Alcohol intake Viral exposures Lipase LFTs GB US
Diagnosis 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)
Pancreatic Source - Biliary obstruction - Bowel obstruction - Perforated ulcer - Appendicitis - Mesenteric ischemia - Peritonitis
Parotitis DKA Anorexia Fallopian tube Malignancies
Unknown Source
Renal failure Head trauma Burns Postoperative
Salivary
Diagnosis 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%
Diagnosis
Elevated ALT > 3x normal (in a non-alcoholic) has
a positive predictive value of 95% for GS pancreatitis
Diagnosis Imaging
CT
- Excellent pancreas imaging - Recommended in all patients with persisting
organ failure, sepsis or deterioration in clinical status (6-10 days after admission) - Search for necrosis will be present at least 4 days after onset of symptoms; if ordered too early it will underestimate severity - Follow-up months after presentation as clinically warranted for CT severity index of >3
Diagnosis - Imaging
ERCP / EUS
- Diagnostic and Therapeutic - Can see and treat: Ductal dilatation Strictures Filling defects / GS Masses / Biopsy
Diagnosis Imaging
ERCP indications (should be done in the first 72hr)
GS etiology with severe pancreatitis needs sphincterotomy Cholangitis Jaundice Dilated CBD If no GS found sphincterotomy is indicated anyway Poor surgical candidate for laparoscopic cholecystectomy Clinical course not improving sufficiently to allow timely laparoscopic cholecystectomy and intraoperative cholangiogram - Pregnant patient - Uncertainty regarding biliary etiology of pancreatitis
Predictors of Severity
Why are they needed?
- appropriate patient triage & therapy - compare results of studies of the impact of
therapy
Which is best?
Ranson Criteria
Alcoholic Pancreatitis
AT ADMISSION WITHIN 48 HOURS
1. Age > 55 years 2. WBC > 16,000 3. Glucose > 200 4. LDH > 350 IU/L 5. AST > 250 IU/L
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
7-8 100%
Number Mortality
5-6 40%
Glasgow Criteria
Non-alcoholic Pancreatitis
1. 2. 3. 4. 5. 6. 7. 8.
BUN > 16
Arterial PO2 < 60 mm Hg Ca < 8
CT Severity Index
appearance
grade score normal A 0 enlarged B 1 inflamed C 2 1 fluid collection D 3 2 or more collections E 4
necrosis
score score 1-2
none 0
33-50% 4 mortality 0%
> 50% 6
7-10
92%
17%
Balthazar et al. Radiology 1990.
Scoring systems - 3 Ranson criteria - 8 APACHE II points - 5 CT points Organ failure - shock (SBP < 90 mmHg) - pulmonary edema / ARDS (PaO2 < 60 mmHg) - renal failure (Cr > 2.0 mg/dl) Local complications - fluid collections pseudocysts - necrosis (mortality 15% if sterile, 30-35% if infected) - abscess
Goals of Treatment
Limit systemic injury - support and resuscitation effective - decrease pancreatic secretion ineffective / harmful? - inhibit inflammatory mediators ineffective - inhibit circulating trypsin ineffective (too late) - removing gallstones mostly ineffective Prevent necrosis how? Prevent infection - antibiotics (imipenem and ciprofloxacin) probably effective in necrotic pancreatitis - prevent colonic bacterial translocation - removing gallstones variably effective
Refeeding (usually 3 to 7 days) - bowel sounds present - patient is hungry - nearly pain-free (off IV narcotics) - amylase & lipase not very useful here
Rule-out necrosis
- contrasted CT scan at 48-72 hours - prophylactic antibiotics if present - surgical debridement if infected
Nutritional support
- may be NPO for weeks - TPN vs. enteral support (TEN)
Role of ERCP
Gallstone pancreatitis
- Cholangitis - Obstructive jaundice
Metabolic stress - catabolism & hypermetabolism seen in 2/3 of patients - similar to septic state (volume depletion may be a major early factor in the above derangements) Altered substrate metabolism - increased cortisol & catecholamines - increased glucagon to insulin ratio - insulin resistance Micronutrient alterations - calcium, magnesium, potassium, etc
Hypermetabolism
- Increased resting energy expenditure
Catabolism
- Increased proteolysis of skeletal muscle
Mortality
3%
27%
Benefit or harm? - early uncontrolled studies suggested benefit - two retrospective studies (70s & 80s) showed no benefit with TPN in pancreatitis - 1987 randomized study of early TPN vs. IVF alone showed more sepsis, longer stays, & no fewer complications with TPN When to use TPN? - jejunal access is unavailable - ileus prevents enteral feeding - patients in whom TEN clearly exacerbates pancreatitis
studies - late 80s patients who received jejunal feeding tubes at the time of surgery, did well with early post-op enteral support - 1991 randomized study of early TPN vs. early TEN post-op showed no short-term difference - 1997 early TPN vs. early TEN (Peptamen) via nasojejunal tube in 32 patients showed no difference except 4x less cost & less hyperglycemia - 1997 similar study showed fewer complications and lower cost without change in length of stay - 1998 similar study showed more sepsis and organ failure in the TPN group
Conclusions
Acute pancreatitis is a self-limited disease in
which most cases are mild.
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