CHAPTER 24
Pancreatitis: Acute and Chronic
Evangelia Davanos, PharmD, BCNSP, CNSC • Ashley Steinberg, MD
Pancreatitis, an inflammatory disease of the pancreas, may be classified as acute or chronic. Most cases of acute pancreatitis are caused by either alcohol intake or gallstones. The clinical course may be mild, subsiding within 48 to 72 hours with conservative therapy, or may progress to pancreatic necrosis with rapid deterioration of the respiratory system and other organ systems. Subsequently, severe cases of pancreatitis may lead to sepsis and death. Treatment is largely supportive, with intravenous hydration and parenteral analgesics being the mainstay of therapy. Treatment failure mandates a search for complications such as abscesses, pseudocysts, or pancreatic necrosis, which may require antibiotic therapy.
The etiology of chronic pancreatitis is similar, with alcoholism as the predominant factor in up to 50% of cases (DiMagno & DiMagno, 2012). Pancreatic duct obstruction, smoking, hereditary factors, or hypertriglyceridemia may all cause chronic pancreatitis. Persistent inflammation of the gland leads to fibrosis and a loss of exocrine and endocrine parenchyma. Initially, pain is the predominant symptom until acinar tissue is completely effaced. Steatorrhea may occur at that point and becomes the main concern, as it may lead to malabsorption and nutritional deficiencies (Duggan, O’Sullivan, Feehan, Ridgway, & Conlon, 2010).
ANATOMY, PHYSIOLOGY, AND PATHOLOGY
The pancreas is a tadpole-shaped gland of soft consistency. It is more than 6 inches long and has a finely lobulated surface. It lies somewhat obliquely, immediately behind the peritoneum of the posterior abdominal wall, and slopes from a large head, up through a neck and body, toward a narrow tail. The head lies in the C curve of the duodenum, and part of its posterior surface is prolonged and wedge-shaped, forming the uncinate process. The main pancreatic duct (Wirsung) is continuous from the tail to the head and joins the common bile duct at the ampulla of Vater, which then opens into the duodenum. The accessory pancreatic duct (Santorini) drains the uncinate process and lower part of the head and also opens into the duodenum separately from the main duct, although the two ducts often communicate. The blood supply is from the splenic and pancreaticoduodenal arteries; the corresponding veins drain into the portal system.
The pancreas has both endocrine (internal) and exocrine (external) secretory properties. The endocrine component of the pancreas consists of the islets of Langerhans. These produce insulin, glucagon, and somatostatin, which all play a major role in the metabolism of food. Most of the endocrine tissue is contained in the tail and distal body of the pancreas. The exocrine pancreas consists of glandular, secretory units called acinar cells. These produce and secrete pancreatic juice, which has two important components: bicarbonate, which neutralizes stomach acid, and digestive enzymes, which are secreted into the duodenum via the main pancreatic duct and aid in the digestions of fat, protein, and carbohydrates.
ACUTE PANCREATITIS
Epidemiology
An inflammatory process of the pancreas may further involve other regional tissues or remote organ systems. The process can be mild or severe; mild is associated with minimal organ disruption and an uneventful recovery, and severe sometimes progresses to cell necrosis and death. Seventy-five percent of cases of acute pancreatitis fall into the mild category. The incidence of acute pancreatitis has been steadily increasing over time, negatively influencing the burden on health care costs worldwide (Spanier, Bruno, & Dijkgraaf, 2013). According to the National Digestive Diseases Information Clearinghouse, pancreatitis has a prevalence of 1.1 million people. In 2003, there were 17 cases of acute pancreatitis per 100,000 people; in 2004 pancreatitis accounted for 489,000 hospitalizations and 3,480 deaths (National Digestive Diseases Information Clearinghouse, 2013). Histologically, acute pancreatitis is characterized by a wide spectrum of lesions, including edema, fatty necrosis, parenchymal necrosis, and hemorrhage.
Alcoholism | Idiopathic |
Cholelithiasis | Infections |
Drugs | Pancreas divisum |
Hypercalcemia | Trauma |
Hypertriglyceridemia | ERCP |
ERCP, postendoscopic retrograde cholangiopancreatography.
Acute pancreatitis is seen more frequently in men, specifically between the ages of 40 and 60 years. Although there are many causes of acute pancreatitis (Table 24.1), 40% to 70% of cases are caused by gallstones and 25% to 35% of cases are caused by alcohol use (Tenner, Baillie, DeWitt, & Vege, 2013; d2j7fjepcxuj0a.cloudfront.net/wp-content/uploads/2013/09/ACG_Guideline_AcutePancreatitis_September_2013.pdf).
Other, rarer causes make up the final 10%. Recently, postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis has been noted to be an increasingly prevalent cause of acute pancreatitis, with the incidence associated with diagnostic and therapeutic ERCP being 0.4% to 1.5% and 1.6% to 5.4%, respectively (Arata et al., 2010).
History and Physical Examination
Clinically, abdominal pain, tenderness, and raised serum concentration of pancreatic enzymes are the most common features (Russell, 2004). Signs and symptoms typically include sudden epigastric pain radiating to the back, associated with nausea and vomiting. A history of gallstone disease should be initially ascertained with additional ultrasound imaging. If there is no suggestion of cholelithiasis on ultrasound, further questioning into the history of alcohol intake should be performed, as usual causes are underlying cholelithiasis and excess alcohol intake.
Physical findings of acute pancreatitis include fever, tachycardia, and epigastric tenderness with guarding. Rebound tenderness may be elicited if the pancreatitis is severe and has led to peritonitis. Hypotension and tachypnea are indicative of severe pancreatitis, as are decreased breath sounds from pleural effusion (effusion fluid cytology will show an increase in pancreatic enzymes). Rarely, there are ecchymoses on the flanks (Grey-Turner sign) or in the periumbilical region (Cullen’s sign).
Approximately, half of the patients with acute pancreatitis recover spontaneously, as the disease has a self-limiting nature. There is a 10% mortality rate, with almost half of deaths within the first 2 weeks owing to multiorgan failure and later deaths caused by pancreatic infection (Mutinga et al., 2000). Initial prognostic criteria for acute pancreatitis were developed by Ranson et al. (1974) and are shown in Table 24.2. Based on the Ranson criteria, if three or fewer of these signs are present, the mortality rate approaches 1%, and rarely leads to serious illness. If four or more signs are present, the mortality rate can reach 25%, and about 50% of patients become seriously ill. For patients admitted in the ICU, in order to determine severity of disease, along with the Ranson criteria, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score may be calculated (an APACHE II score calculator can be found at: www.sfar.org/scores2/apache22.html).
Current Medical Therapies for Inflammatory Bowel Disease |
ADMISSION | AT 48 HOURS |
Age >55 years | Hematocrit drop >10% points |
White count >16,000/mm3 | BUN rise >5 mg/dL (>1.8 mmol/L) |
Blood glucose >200 mg/dL (>11 mmol/L) | Arterial PO2 <60 mmHg |
Serum LDH >350 IU/L | Base deficit >4 mEq/L |
AST >250 IU/L | Serum calcium <8 mg/dL (<2 mmol/L) |
Estimated fluid sequestration >6 L |
BUN, blood urea nitrogen; LDH, lactate dehydrogenase; AST, aspartate aminotransferase.
Complications of acute pancreatitis include those common to the pancreas itself, to adjacent organs, or to various systems within the body. Pseudocysts, abscesses, and hemorrhage into the pancreas are the most common complications. The latter may require surgical intervention, whereas pseudocysts are managed conservatively unless they enlarge over time or cause significant impediment secondary to pain. After the pancreas, the first organ system that is affected is usually the lungs, with adult respiratory distress syndrome developing early in severe acute pancreatitis. Pancreatitis can cause massive sequestration of fluid leading to third spacing, causing severe hypotension and hypovolemic shock. Pleural effusion and atelectasis can occur, as well as renal failure. Electrolyte abnormalities are also common, and electrolytes must be constantly monitored and repleted as necessary.
Severe acute pancreatitis can lead to pancreatic infection and generalized sepsis as a result of bacterial translocation from the gut, which permits colonization of the necrotic tissue. Common bacteria implicated in such infection include Enterobacteriaceae.
Diagnostic Studies
LABORATORY TESTS
Serum amylase is most frequently used to detect pancreatitis. However, elevated amylase levels occur only in acute exacerbations, so the usefulness of this test is limited. Elevation of the serum lipase level is more specific but less sensitive than serum amylase analysis; however, it is often drawn concurrently with serum amylase to increase its sensitivity and specificity.
A complete blood count, a basic metabolic panel, and a hepatic panel, along with lactate dehydrogenase and triglyceride levels, should all be checked. An elevated hematocrit may be noted due to hemoconcentration, as serum is lost into the peritoneal and retroperitoneal spaces. The white blood cell count is usually elevated, as in most infectious processes. Hypocalcemia is common in pancreatitis, and occurs secondary to failure of homeostatic mechanisms due to destruction of islet β-cells. Hypocalcemia may also be caused by the precipitation of calcium soaps, caused by calcium deposition into the retroperitoneum from the breakdown of free fatty acids. Hypokalemia and hypomagnesemia are the other two most frequent electrolyte abnormalities that may be seen. Hyperglycemia may occur due to decreased insulin production or increased glucagon levels. Increased bilirubin and alkaline phosphatase values may reflect cholestasis due to compression of the common bile duct. Triglyceride levels are generally elevated, but a level above 1,000 mg/dL would implicate an underlying hyperlipidemic disorder, usually a type V lipid profile, which may be the sole cause of the pancreatitis.
Imaging Studies
A flat plate of the abdomen may reveal calculi in the gallbladder or sentinel loops (localized gas collections in loops of bowel overlying the pancreas) in a few cases. It will also rule out the presence of free air under the diaphragm, which would signify a perforation of a hollow viscus. Diffuse stippled calcification is seen in about 30% of patients with chronic pancreatitis; however, an abdominal x-ray often will not aid in diagnosis.
Gallstone disease should be considered first in most patients, and hence an ultrasound is often necessary. Ultrasonography is the most useful initial test, because of ease and availability, and it can also be used to differentiate between a phlegmon (a solid inflamed mass of pancreatic tissue that subsides spontaneously) and a pseudocyst (a cystic collection of fluid and necrotic debris without a definitive formed wall).
CT of the abdomen is not always necessary, especially in cases of acute pancreatitis that are not exhibiting signs of severe pancreatitis and have rapid clinical improvement. However, in cases where no etiology can be found, and/or in cases where there is rapid deterioration of clinical status, a CT should be done. A CT of the abdomen should be utilized to see if there is pancreatic necrosis, gallstones, pseudocysts, or an abscess (Thoeni, 2012). The presence of necrosis is an indicator of more severe disease. A more specific CT scan called a CT with pancreatic protocol can aid in diagnosis by more accurately delineating the pancreas; in this study, 2.5 to 3 mm cuts are made (as compared to 5 mm on a normal CT scan) and enhancement is delayed.
If acute pancreatitis is caused by gallstones, an ERCP with sphincterotomy and stone extraction should be done. Otherwise, ERCP exacerbates acute pancreatitis and should be avoided.
Treatment Options, Expected Outcomes, and Comprehensive Management
Hospitalization is necessary for acute pancreatitis. Treatment is largely supportive, consisting of intravenous fluid replacement, nutrition support, electrolyte balance, pain management, and prevention of infections. Due to fluid moving from the intravascular space to the peritoneum, patients may become hypovolemic, and adequate fluid resuscitation is necessary with 0.9% normal saline or Ringer’s lactate. Once the fluid deficit is corrected, a continuous infusion should start for maintenance of fluid provision (35 mL/kg/d). Urine output should be monitored as an indicator of the adequacy of hydration. Pain can best be controlled with opioids such as morphine and hydromorphone, and patient-controlled analgesia (PCA) can be very effective. Although it used to be believed that morphine and opioids can exacerbate pancreatitis due to their effect on the sphincter of Oddi, there are no data to support that theory (Toouli et al., 2002).
Guidelines for the management of acute pancreatitis from the American College of Gastroenterology (Tenner et al., 2013) can be found at http://d2j7fjepcxuj0a.cloudfront.net/wp-content/uploads/2013/09/ACG_Guideline_AcutePancreatitis_September_2013.pdf
Nutrition Support
Nutrition support in acute pancreatitis is very important in order to prevent further protein catabolism and worse outcomes. Malnutrition has been shown to worsen the outcome of the disease and it occurs in 50% to 80% of chronic alcoholics; because alcohol abuse is one of the major factors causing pancreatitis, malnutrition is of great concern in these patients. During acute pancreatitis, the inflammatory processes that occur are similar to those in sepsis or trauma, leading to increased protein catabolism, an inability of exogenous glucose to inhibit gluconeogenesis, increased energy expenditure, and increased insulin resistance. Specialized nutrition support (enteral or parenteral nutrition) in acute pancreatitis patients is indicated when it is expected that the patient will have inadequate oral intake for 5 to 7 days, unless the patient is malnourished prior to the pancratitis insult. In cases of mild pancreatitis, it is expected that resolution of pain and initiation of diet will occur within 3 to 7 days, and therefore there is no need for specialized nutrition support (Gianotti et al., 2009). Parenteral nutrition has no role in pancreatitis unless enteral nutrition cannot be tolerated or cannot be initiated due to contraindications (Mirtallo et al., 2012). Many providers worry about enteral nutrition stimulating the pancreas and therefore worsening the disease. However, nasogastric tubes may be used, although feeding tubes that are passed below the ligament of Treitz (jejunal tubes) should not have that effect. In fact, jejunal feedings have been proven to be beneficial in severe acute pancreatitis, leading to decreased mortality and a shorter length of stay in the ICU (Hegazi et al., 2011).
Teaching and Self-Care
Patients need to be educated about what increases their risk for developing acute pancreatitis. Risk factors must be reviewed extensively, and all risk factors must be addressed. Because alcohol consumption is such a common cause of pancreatitis, the use and abuse of alcohol must be explored. Hypertriglyceridemia may also be a cause of pancreatitis, so patients should be educated on diets for decreasing triglyceride levels, such as a low-fat, low-cholesterol diet; only when this dietary therapy is insufficient should further therapies be instituted. If the cause for pancreatitis is cholelithiasis, discussing the possibility of a cholecystectomy may be warranted. A laparoscopic cholecystectomy may have to be performed when enzymes are trending down and clinical symptoms are resolving.
Complementary Therapies
The use of probiotics has been studied in acute pancreatitis but due to increased mortality observed with their use, they cannot be recommended at this time (Besselink et al., 2008). Some complementary therapies for pain management are noted in the section on chronic pancreatitis. In the acute, hospital setting, opioid medications or potent nonsteroidal anti-inflammatories are usually administered for pain management.
Referral Points and Clinical Warnings
Although acute pancreatitis may subside spontaneously, it is a potentially life-threatening disorder and should be treated as such. Patients with suspected cases should be evaluated urgently for admission to the hospital. A gastroenterologist and a surgeon may have to be consulted, especially when related to gallstone disease. In addition, social workers, dietitians, and possibly psychologists should often be involved, depending on the risk factors/causes for pancreatitis and the severity of the disease.
CHRONIC PANCREATITIS
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