Pathophysiology
Summary
Pancreatitis is a complex disorder of the pancreas characterized by inflammation and autodigestion of the gland. It can manifest in two major forms: acute pancreatitis and chronic pancreatitis.
The underlying pathology in acute pancreatitis primarily involves the premature activation of trypsinogen to its active form, trypsin, a protease responsible for digesting dietary proteins. This early activation sets off a cascade of other pancreatic enzymes, leading to inflammation and acute pancreatitis. Excess lipase contributes to the autodigestion of adipose tissue, resulting in fat necrosis and calcium precipitations that are visible on histology.
The most common etiological factor for acute pancreatitis is gallstones, often due to the obstruction of the common bile duct. Chronic alcohol abuse is the 2nd leading cause, primarily through direct toxic injury and increased viscosity of pancreatic secretions. Hypertriglyceridemia, such as familial hyperlipidemia syndromes, can also cause acute pancreatitis. Additional causes include medications, trauma (seatbelt trauma), and ERCP.
Clinically, acute pancreatitis often presents with sharp, epigastric pain radiating to the back, accompanied by nausea, vomiting, & fever. Diagnostic markers include increased serum amylase and, more specifically, increased serum lipase.
Acute pancreatitis may complicate further into more severe conditions, such as the formation of a pseudocyst—liquified pancreatic tissue walled off by a capsule of fibrous granulation tissue. In extreme cases, acute pancreatitis may progress to acute necrotizing pancreatitis, where gross pathology reveals white, chalky areas of fat necrosis and red-black regions of hemorrhage. Additional complications include acute respiratory distress syndrome (ARDS), caused by the breakdown of surfactant in the lungs, and splenic vein thrombosis.
Chronic pancreatitis most commonly arises in chronic alcohol abuse, though many cases are idiopathic. Cystic fibrosis is another notable etiology. Over time, chronic pancreatitis can lead to fibrosis, calcification, & atrophy of the pancreatic tissue. Imaging studies like CT scans and ultrasound reveal calcified concretions throughout the pancreas. Recurrent pseudocysts are also a frequent complication.
Clinically, chronic pancreatitis is associated with recurrent pseudocyst formation, as well as steatorrhea due to decreased lipase secretion. This malabsorption of lipids also leads to deficiencies in fat-soluble vitamins A, D, E, and K. Diabetes is also a potential complication due to the destruction of the islets of Langerhans and impaired insulin secretion. Chronic pancreatitis is also known to increase the risk of pancreatic adenocarcinoma.
Lesson Outline
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FAQs
The most common cause of acute pancreatitis is gallstones, which obstruct the common bile duct and lead to premature activation of trypsin, initiating pancreatitis. Chronic alcohol abuse is the second leading cause, causing direct toxic injury to the pancreas and increasing the viscosity of pancreatic secretions. Other factors like hypertriglyceridemia, certain medications, and trauma can also cause acute pancreatitis. For chronic pancreatitis, alcohol abuse is the predominant cause, although some cases are idiopathic or related to conditions like cystic fibrosis.
Pancreatic injury or duct obstruction can cause premature activation of trypsin, a protease enzyme. This early activation sets off a cascade of other pancreatic enzymes, leading to inflammation and acute pancreatitis. Lipase, another enzyme, contributes to the autodigestion of adipose tissue, resulting in fat necrosis. This process also leads to the binding of fatty acids to calcium ions, resulting in calcium precipitations that are visible on histology.
Acute pancreatitis often manifests as sharp epigastric pain radiating to the back, accompanied by nausea, vomiting, and fever. Lab tests often show elevated levels of serum amylase and lipase, with lipase being more specific for pancreatitis. In severe cases, hypocalcemia may occur due to the binding of free fatty acids to calcium ions. Fluid accumulation around the pancreas can also occur, leading to hypovolemia.
Chronic pancreatitis leads to a gradual loss of both exocrine and endocrine functions of the pancreas. Reduced exocrine function manifests as steatorrhea, or high lipid content in stool, due to decreased lipase secretion. This results in malabsorption of lipids and deficiencies in fat-soluble vitamins A, D, E, and K. On the endocrine side, destruction of the islets of Langerhans leads to reduced insulin secretion, causing diabetes and elevated blood glucose levels.
Acute pancreatitis presents with symptoms like sharp abdominal pain, nausea, vomiting, and fever. Histologically, it shows features like fat necrosis and calcium precipitations. In contrast, chronic pancreatitis leads to fibrosis, calcification, and atrophy of the pancreas over time. It presents with calcified concretions visible on imaging, as well as symptoms related to malabsorption and diabetes due to loss of pancreatic function.
