ACUTE PANCREATITIS

ACUTE PANCREATITIS:
Symptoms:
Abdominal pain: Diffuse throughout the entire upper abdomen. May be localized in the midepigastrum and LUQ or RUQ. Radiation to the back. Pain reaches maximum intensity within 10-20 min and may appear like a perforated ulcer. Pain is moderate to severe. Can be unbearable and refractory to PO narcotics. Steady and boring. Little fluctuation in pain. No relief by change of position of bed.
Nausea and vomiting: Frequent. May be severe and last several hours. May turn into dry heaves. Vomiting does not relieve the intensity of the pain. Even with gallstone pancreatitis, there is no temporal relationship between eating and the onset of pain.
Physical Exam:
Vitals: HR may be ( to 100 to 150. BP may start high and then go lower as there is third spacing. Temp: may be normal and then rise to 101 to 103.
Respiration: May be shallow if there inflammatory exudate on the diaphragm. Limited diaphragmatic excursion if abd causes splinting of the abdomen. Dullness to percussion due to pleural effusion.
Abdomen: Tenderness in upper abdomen. Guarding, percussion tenderness. Distention of abdomen. Rarely rigid. Grey Turner sign: ecchymoses in one or both flanks. Cullen sign: ecchymoses of the periumbilical region due to pancreatic exudate
Lab diagnosis:
Amylase: Reflects leakage of pancreatic isoamylase into the systemic circulation. ( 75% of acute pancreatitis. Remains ( for 5 to 10 days. Usually 3x Nl. Limitations: Amylase not ( in all cases of pancreatitis.
Lack of specificity: Acute pancreatitis, pancreatic carcinoma, acute cholecystitis, common bile duct obstruction, perforation of viscous, intestinal ischemia, intestinal obstruction ,acute appendicitis, renal insufficiency, and many more.
Lipase: ( in pancreatitis to 3x normal. Normal is 20-250. More specific. Almost all lipase originates from the pancreas.
Limitations:
( Renal insufficiency: Lipase ( only when creatinine clearance is < 20 ml/min. Lipase level is usually 2x normal.
( Acute intra-abdominal conditions: Usually less than 3x normal.
Standard blood tests:
( ( WBC, serum glucose, AST, ALT, Alk phos, and serum bilirubin.
( Biliary vs. alcoholic pancreatitis: ALT > 150 96% specific for gallstone pancreatitis. However, sensitivity was only 48%. Therefore a level of < 150 does not exclude gallstone pancreatitis
Radiologic features:
Survey film: Anterior displacement of the stomach. Ileus of one or more loops of jejunum (called the sentinel loop), or any of the small intestine. Colon cutoff sign: Inflammation from head of pancreas that spreads to the proximal transverse colon that leads to spasm of this area and dilatation of the ascending colon. Possible calcified gallstones.
Chest radiography: limited diaphragmatic excursion, pulmonary infiltrates, or pleural effusion.
Barium Studies: Replaced by CT
Ultrasound: Presence of gallstone. Dilated CBD. Enlargement of pancreas
CT: Most common technique for evaluation of acute pancreatitis. The indications are:
( If mesenteric infarction or perforated ulcer cannot be excluded.
( Staging pancreatitis
( Defining the complications.
MRI: Same information as CT. Not currently used.
Differential Diagnosis:
Biliary Colic
Perforated hollow viscus
Mesenteric ischemia
Closed loop intestinal obstruction
Inferior wall MI
Dissecting aneurysm
Ectopic pregnancy
Predisposing conditions:
Gallstones: Responsible for 30 to 75% of all cases of acute pancreatitis. Caused by lodging of gallstone in the ampulla of vater. Pathogenesis remains undetermined. Thought to be obstruction of pancreatic outflow rather than regurgitation of bile into the pancreas. Others cases are caused by stones too small to image.
Alcohol: 30% of cases. Mechanism is unclear.
Hyperlipidemia: 4% of cases. Most occur in pts with uncontrolled DM and a Hx of hypertriglyceridemia. Typically pts will need levels greater than 1000. Levels between 500 and 1000 may occasionally cause pancreatitis.
Hereditary pancreatitis: Autosomal dominant with variable penetrance. Need identification of at least two family members. Episodes begin in childhood.
Hyperparathyroidism and Hypercalcemia: 0.5% of cases. Mechanism unclear.
Structural abnormalities:
Medications:
( Immunosuppressive agents
( Sulfonamides
( Abx: Metronidazole, tetracycline, and nitrofurantoin
( Valproic acid
( Corticosteroids
( Furosemide
( Estrogens
( Aldomet
( Pentamidine
( Octreotide
( Didanosine
Infectious agents:
( Viral: Coxsackie B, EBV, CMV, varicella, and Hep A, Hep B, Hep C.
( Bacterial: Tb, leptospirosis, brucellosis.
( Candida albicans
( Parasitic: C. Sinensis and ascaris.
Other: Vascular dz, ERCP, post-operative, pancreatic trauma, cystic fibrosis, pregnancy, and miscellaneous.
Classification by Ranson criteria:
These are signs that have prognostic significance. The criteria on admission are measures of the intensity of local inflammation. The other 6 reflect the development of systemic complications and the harmful effects of third spacing fluid. The higher the number of Ranson criteria a pt has the more severe the pancreatitis. A large study showed that a ranson score of 1.6 correlated with mild pancreatitis, 2.4 with severe pancreatitis, and 5.6 with lethal pancreatitis.
On admission:
Age > 55
WBC > 16,000
Glucose > 200
AST >250
LDH > 350

During first 48 hrs
1) Hct ( of > 10: a measure of hemoconcentration
2) BUN ( of >5: reflects renal failure
3) Ca <8: loss of nonionized calcium associated w/loss of serum albumin, fat saponification, and complex cascade ( calciuria.
4) Pa O2 < 60: respiratory failure
5) Base deficit > 4: metabolic acidosis and shock
6) Fluid sequestration > 6 L: difference between amount of fluids administered IV vs. losses from urine and NGT.

These criteria are good only for the first 48 hrs. These criteria are most useful to exclude severe disease. The overall sensitivity for the criteria is 57 to 85%, specificity is 68 to 85%, the positive predictive value is 50% and negative predictive value of 90%.
Medical Management:
Fluid Resuscitation: Large amounts of fluid are lost secondary to exudation of blood and plasma protein into the retro peritoneal space. There is also ( the formation and release of kinin peptides ( vasodilatation and ( vascular permeability. Fluid resuscitation prevents hypotension and renal insufficiency. Requirements may be in excess of 6 L per day and can exceed 10L to maintain adequate vol. Swan-Ganz may be helpful in determining adequacy of fluid resuscitation. Colloid should be used if albumin is < 2 g/l. If Hct ( to 25 then PRBC should be used to maintain Hct at 30.
Respiratory care: Major problems are atelectasis, pneumonia, pleural effusions, CHF and fatigue. ARDS may also develop. O2 should be measured constantly and given if needed. ARDS occurs on 2nd to 7th day of illness.
Cardiovascular care: ( in cardiac index and ( in peripheral vascular resistance. IV use of dopamine can help maintain systemic blood pressure.
Relief of pain: PCA MSO4 is preferred over Meperidine.
Nutritional support: TPN for 3 to 6 weeks. Switch to oral feedings if abdominal pain and tenderness have lessened, organ dysfunction improved, and pt is hungry. Start with small feedings.
Local Complications
1. Pancreatic inflammatory mass (phlegmon).
2. Pancreatic infection of necrotic tissue
3. Pancreatic abscess (bacterial infection)
4. Pancreatic pseudocyst (collection of fluid and debris which, in contrast to true cysts, do not have epithelial lining)
5. Pancreatic ascites (leak of pancreatic duct)
6. Involvement of adjacent organs by necrotizing pancreatitis
Systemic Complications
1) Pulmonary: Hypoxia and ARDS can occur due to ( surfactant due to circulating phospholipases, alveolar capillary leak.
2) Cardiovascular: ( intravascular vol or shock may occur due to "third spacing" of fluid into edematous retroperitoneal space. Kallikrein activation and bradykinin production can cause ( capillary permeability, vasodilation, and hypotension.
3) Hematologic: Circulating trypsin activates thrombin and plasmin with resulting DIC. ( Hct may occur due to retroperitoneal bleeding.
4) Gastrointestinal: GI bleeding may occur due to pancreatic inflammation affected the stomach, duodenum, or peri-pancreatic blood vessels, or due to gastric varices resultant from splenic vein thrombosis. Nausea and vomiting may occur due to ileus of small bowel adjacent to pancreatic inflammation.
5) Renal: Impaired kidney function due to hypoperfusion of the kidneys from ( intravascular volume.
6) Metabolic: Hypocalcemia may occur due to precipitation of Ca in fatty soaps in the retroperitoneum (saponification of Ca by fatty acids in areas of fat necrosis), ( serum albumin, and/or ( PTH secretion.
7) CNS (psychosis)
8) Fat necrosis. Occurs in pancreas and in other sites, such as subcutaneous tissue. Related to release of lipase and phospholipase.
9) Endocrine. Hyperglycemia may occur if insulin production is impaired. Need to have 90% destroyed before get problem.
10) Fevers. Related to pancreatic inflammation and cytokine release.
11) Ascites: fluid leaking from pancreas. ( amylase and lipase.
12) Pseudocyts: Not true cysts. Still dealing with residual and fluid collection. About 6 weeks. Some will resolve on their own. Some need more active treatment.
CHRONIC PANCREATITIS
Chronic inflammatory process of the pancreas which generally manifests as pain and/or malabsorption. It can cause exocrine and endocrine insufficiency, especially when >90% of pancreatic function impaired.
Etiology
*****Alcohol >80%****
Idiopathic
Cystic Fibrosis: cause of occult pancreatitis.
Hereditary
Protein malnutrition
Pathophysiology
Uncertain. Associated with ( precipitation of protein (inspissated enzymes) w/in ducts ( duct obstruction, dilation, fibrosis, and calcification. Induced stone formation w/in ducts in pancreas.
Recurrent pancreatitis ( Chronic pancreatic changes.
Alcohol toxic to pancreas. Disrupts normal defenses against autodigestion.
Abnormal trypsin resistance to trypsin degradation.
Clinical Features
1) Epigastric pain: constant or intermittent. Etiology of pain unclear, but may be related to pancreatic duct/tissue HTN (actual stretching) or to peri-pancreatic nerve damage.
2) Steatorrhea occurs when >90% of gland ceases to function. If from pancreatic. Do they see oil drops in stool. Has to be pancreatic insufficiency. Maldigestion.
3) DM:
4) Protein maldigestion is less common than fat maldigestion.
5) Malabsorption of fat soluble vitamins (ADEK) and vitamin B12 may occur. Vitamin B12 deficiency occurs because B12 binds to non-intrinsic factor proteins which must be cleaved by pancreatic enzymes to allow binding to intrinsic factor for absorption.
Diagnostic Evaluation
Unfortunately no clinical "gold standard" exists. Pancreatic biopsy is generally not performed for fear of inducing acute pancreatitis. Severe cases are easy to diagnose with pancreatic calcifications on xray, steatorrhea, and diabetes mellitus.
Anatomic Imaging Studies
( Abd radiograph ( calcification in severe cases.
( Ultrasound (trans-abdominal or endoscopic) - shows calcification, thickening pancreatic duct wall, dilated and irregular pancreatic duct, and lobular appearance
( CT scan - shows calcifications and a dilated pancreatic duct
( ERCP - shows dilated and irregular pancreatic duct with strictures, possible stones, and dilated side branches.
Functional Studies
1. Qualitative and quantitative fecal fat: > 7 gm in 24 hrs will confim diagnosis.
2. Secretin stimulation test.: release of pancreatic enzymes and release of bicarb.
3. Bentiromide test.
Management
1. *****Avoid alcohol *****
2. Long-term narcotic pain medication is often required.
3. Tricyclic antidepressants can help raise sensory pain threshold.
4. Surgical or endoscopic treatment may help if there is a focal pancreatic duct stricture.
5. Oral ingestion of pancreatic enzymes results in negative feedback to the pancreas, decreases enzyme secretion, improves steatorrhea, and may improve pain in mild-moderate severity cases.
6 Octreotide may have a role in selected cases.
HEREDITARY PANCREATITIS
Autosomal dominant disease with 80% penetrance.
Symptoms: begin before age 20. Epigastric pain and ( pancreatic enzymes. Symptoms may be mild, or may appear as acute or chronic pancreatitis.
Abd radiographs ( calcification in approximately 50% of pts.
There is ( risk of pancreatic cancer ( ~ 40% risk by age 70.
Mutation in the cationic trypsinogen gene on Ch 7 ( abnormality in the trypsinogen molecule which inhibits degradation by trypsin in a feed-back ioop. Under normal circumstances, there is a low level of trypsinogen autoactivation in the pancreas. Any activated trypsin within the pancreas is inhibited by trypsin inhibitor. However if there is excessive trypsin activation which exceeds the amount of trypsin inhibitor, then trypsin can feedback on itself and hydrolyze trypsin to prevent activating the cascade of pancreatic enzymes. In patients with hereditary pancreatitis, activated trypsin will not be inactivated, and therefore will lead to generalized digestive enzyme activation leading to pancreatitis.