Acinar cells secrete 1-2 L/day of isotonic fluid (water, electrolytes, pancreatic enzymes)

Primary Components

1.  Bicarbonate

• neutralizes gastric acid in small intestine
• provides appropriate pH for maintaining activity of pancreatic enzymes

2.  Digestive Enzymes

• secreted as zymogens which are activated in the duodenum
• regulation of secretion is complex and depends on hormonal and neuronal mechanisms
• 2 hormones: secretin and CCK are important in post-prandial secretion
• Proteolytic: trypsinogen, chymotripsinogen, procarboxypeptidase, protealase
• Amylolytic: amylase
• Lipolytic: lipase, phospholipase A, carboxylesterase lipase
• Nucleolytic: ribonuclease
• Other: trypsin inhibitor, colipase

A form of Acute Pancreatitis

• Milder and less painful than necrotizing
• Limited to pancreas and surrounding area

A form of Acute Pancreatitis

• More painful and severe than interstitial
• Necrosis in and around the pancreas
• Higher risk of infection, sepsis, organ failure, and death

Events that initiate injury

• activation of zymogens within acinar cells
• pancreatic ischemia
• pancreatic duct obstruction

Secondary events that determine duration and severity

• release of active pancreatic enzymes -- local or distant tissue damage
• cytokine generation --> inflammation --> TNF-α, IL-1
• release of vasoactive substances --> capillary permeability

Net effects

• vascular damage - ischemia and edema
• tissue damage and cell death

Pancreatic infections may result from translocation of colonic bacteria due to increase intestinal permeability

1. Abdominal Pain

• epigastric - radiates to either upper quadrants or the back
• sudden onset and steady with no decrease in pain with repositioning
• intensity - "knife-like"

2. Nausea/Vomiting

3. Epigastric tenderness

4. Abdominal distension

5. Fever

Symptoms suggestive of severe pancreatitis

• shock
• respiratory distress
• absent bowel sounds
• ARF
• moderate-severe hypocalcemia

1. Increased WBC (10-25 K)
2. Serum Amylase (> 3x ULN)

• rises within 4-8 hrs, pks @ 24 hrs, returns to nl within 8-14 days
• persistent elevations suggest pancreatic necrosis and complications

3. Serum Lipase (> 3x ULN)

• longer t_1/2 than amylase -- can be elevated after amylase has returned to normal
• more specific than amylase for pancreatic disease

4.  ↑ bilirubin (mild), ↑ ALP, ↑ AST/ALT, ↓ albumin

Fluid Resuscitation

• agressive fluid resuscitation is KEY
• Initial fluid resuscitation --> isotonic crystalloids
• IV colloids may be needed to aid in restoration of intravascular volume
• Correct electrolyte deficiencies (Ca, K, Mg)

Nutrition

• Oral nutrition held at onset of attack
• Mild attack -- resume oral feeding within several days
• Severe dz -- nutritional deficits develop rapidly
• If expect NPO > 1 week or pt. malnourished -- begin parenteral or enteral feedings immediately

Parenteral vs Enteral

• Both are effective
• Parenteral -- increase risk of infection, hyperglycemia, and risk of increasing triglycerides
• Enteral -- safer, less expensive, and may prevent infection by decreasing risk of bacterial translocation across the GI wall
• Enteral -- the tip of the OG/NG tube should be in the jejunum (J-tube) -- distal to the bile duct

Treatment for Acute Pancreatitis

• Old drug of choice
• Little effect on sphincter of Oddi
• Not as effective as other narcotics -- requires high doses
• Drug metabolite accumulates in renal failure, increasing risk of adverse CNS events (seizures, psychosis)

Treatment for Acute Pancreatitis

• Good pain relief
• May lead to spasm of sphincter of Oddi
• Increases serum amylase
• Possible etiology of pancreatitis

Treatment for Acute Pancreatitis

• Similar effects of morphine
• May be better tolerated by patients (< ADRs)

Treatment for Acute Pancreatitis

• Possibly best choice in acute pain management
• Potent analgesic
• Little effect on sphincter of Oddi
• Well tolerated
• Lower accumulation risk than hydromorphone and morphine
• Very expensive

Treatment for Acute Pancreatitis

• Benefit in patients who need high dose and frequent administration of narcotic dosing

Treatment for Acute Pancreatitis

• Potent inhibitor of pancreatic enzyme secretion, but it also increases sphincter of Oddi pressure and decrease splanchnic blood flow
• Limited to patients with severe disease due to lack of data to support use

• Therapy should be guided by cultures
• High risk patients may benefit (necrotizing pancreatitis with signs of infection, pancreatic abscess or infected pseudocyst)
• Regimen should cover enteric G- and anaerobes
• Commonly used agents -- Imipenem/cilastatin, Fluoroquinolone + metronidazole (PCN allergy)
• Initiate therapy within 48 hrs and continue for 2-3 weeks
• G+ and fungal infections increasing in patients receiving antibiotic prophylaxis -- empiric fungal prophylaxis commonly added

• Slow progression from inflammation to cellular necrosis to fibrosis
• Changes in pancreatic fluid --> environment for formation of intraductal protein plugs --> block small ductules --> progressive structural damage of ducts and acinar cells
• Calcium complexes with protein plugs --> injury and destruction of tissue
• Abdominal pain associated with increased intraductal pressure
• Malabsorption occurs when enzyme secretion decreased by ~ 90% (lipase secretion decreases before proteolytic enzymes, bicarbonate secretion may or may not fail)

Abdominal pain

• constant or episodic
• pain radiates to back
• deep-seated, positional, and frequently nocturnal
• Unresponsive to medication
• May be aggravated by eating
• Nausea and vomiting accompany the pain

Malabsorption

• Steatorrhea
• Azotorrhea
• Vitamin B12 deficiency

Weight loss

Diabetes (late manifestation)

Jaundice

• Serum amylase and lipase usually normal
• WBC count, fluids, and electrolytes are usually normal

• Alcohol abstinence
• Smoking cessation
• Small, frequent meals (6 meals per day)
• Fat restricted diet (50-75 g/day)
• Increased dietary fiber
• Surgical procedures

Chronic Pain Management for Chronic Pancreatitis

• Caution in patients w/ history or current use of alcohol
• Limit to 2 g/day in alcohol-induced pancreatitis

Chronic Pain Management for Chronic Pancreatitis

• Increased risk of GI bleed
• COX-2 for patients at high-risk of GI bleed
• Caution in renal failure

Chronic Pain Management for Chronic Pancreatitis

• 50-100 mg po q 4-6 hrs
• Narcotic-like effect
• Contraindicated in alcohol intoxication
• Caution in elderly and renal failure (CNS effect)

Chronic Pain Management for Chronic Pancreatitis

• Abuse-potential -- concern in alcoholic patients
• Be aware of total APAP dose in combo products
• Numerous combinations, doses, and potencies

Chronic Pain Management for Chronic Pancreatitis

• Celiac nerve block
• Injected into celiac nerve
• Effects last ~ 1 month

• Indicated when steatorrhea and wt. loss are present
• Enteric-coating and increasing gastric pH increases bioavailability of enzymes

Non-Enteric Coated

• Addition of antisecretory agent may increase efficacy
• ADRs -- nausea, cramping, hyperuricemia
• CI -- hypersensitivity to pork protein

Enteric Coated

• Requires fewer capsules/tablets per meal
• Does not require additional antisecretory therapy
• ADRs -- nausea, cramping, hyperuricemia
• CI -- hypersensitivity to pork protein

• Improves efficacy of pancreatic enzyme supplementation by increasing gastric pH and helping to prevent enzymatic degradation in the stomach
• Little or no effect in reducing steatorrhea