Inflammatory disorders of the pancreas are divided into acute and chronic forms. In acute pancreatitis, the function can return to normal if the underlying cause of inflammation is removed. By contrast, chronic pancreatitis causes irreversible destruction of the exocrine pancreas.
Pancreas, the Organ
The pancreas gets its name from the Greek pankreas, meaning “all flesh”; and true to the name it is a pear-shaped complex spongy lobulated organ. Located in the upper left abdomen transversely or horizontally behind the lower part of the stomach, it is about 8 inches long. Extending from the so-called “C loop” of the duodenum to the hilum of the spleen, it is surrounded by small intestine, liver and spleen. To note, the first part of the small intestine is called the duodenum. The pancreas does not have well-defined anatomic subdivisions. Nonetheless, adjacent vessels and ligaments serve to demarcate the organ into a head, body, and tail. The head of the pancreas is located at the juncture where the stomach meets small intestine, the former passing partially digested food into the later.
Functions of the Pancreas
Effectively, the pancreas is two organs packaged into one. Composed of about 1 million cell clusters, the islets of Langerhans scattered in the pancreas serve critical endocrine functions. This endocrine portion constitutes only 1% to 2% of the pancreas, and these cells secrete insulin, glucagon, and somatostatin. Over 95% of the pancreas consists of exocrine tissues and this exocrine portion is a major source of enzymes that are essential for digestion.
The pancreas releases digestive enzymes well in time and in the required quantity. The exocrine glands secrete trypsin to digest protein, amylase for action on carbohydrates and lipase to break down fats. The endocrine Islets of Langerhans release two hormones directly into the bloodstream to properly balance the blood sugar level. Insulin lowers and glucagon raises the sugar level. Thus, the pancreas has a very significant role in the body.
Diseases of the Pancreas
Pancreatitis and Pancreatic Cancer are the main diseases of the pancreas. The most significant disorders of the endocrine pancreas are diabetes mellitus and neoplasms or tumour. [Definition of neoplasm: An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Neoplasms may be benign (not cancer), or malignant (cancer). – The NCI Dictionary of Cancer Terms]
Diseases of the exocrine pancreas include cystic fibrosis, congenital anomalies, acute and chronic pancreatitis, and neoplasms. Pancreas divisum is the most common congenital anomaly of the pancreas. In polycystic disease, the kidneys, liver, and pancreas may all contain cysts. Congenital cysts generally are unilocular.
Endocrine neoplasm or Pancreatitis occurs when pancreatic secretions build up and begin to digest the organ itself. There is inflammation that is acutely painful or chronically progressive. This auto-digestion of the pancreas can be a catastrophic event. The body has evolved a number of “fail-safe” mechanisms to minimize the risk for occurrence of this phenomenon. Still, it occurs.
Acute pancreatitis is a relatively common and reversible inflammatory disorder that varies in severity. Of note, 10% to 20% of cases of acute pancreatitis have no identifiable cause (idiopathic pancreatitis), although a growing body of evidence suggests that many may have an underlying genetic basis.
Acute pancreatitis appears to be caused by auto-digestion of the pancreas by inappropriately activated pancreatic enzymes. The most common cause of acute pancreatitis is the mechanical impaction of gallstones within the common bile duct. Gallstone pancreatitis impedes the flow of pancreatic enzymes. The next common cause is excessive alcohol intake. Overall, gallstones and alcoholism account for greater than 80% of acute pancreatitis cases.
Alcohol consumption may cause pancreatitis by several metabolic mechanisms. Alcohol transiently increases pancreatic exocrine secretion and contraction of the muscle regulating the flow of pancreatic juice. It also has direct toxic effects on acinar cells leading to membrane damage. Finally, chronic alcohol ingestion results in the secretion of protein-rich pancreatic fluid which leads, in process, to the obstruction of small pancreatic ducts.
The basic alterations in acute pancreatitis are:
- Microvascular leakage causing oedema
- Necrosis of fat by lipases
- Acute inflammatory reaction
- Proteolytic destruction of pancreatic parenchyma, and
- Destruction of blood vessels leading to interstitial haemorrhage
Clinical Features of Acute Pancreatitis
Abdominal pain is the cardinal manifestation of acute pancreatitis. Its severity varies from mild and uncomfortable to severe and incapacitating. Acute pancreatitis is diagnosed primarily by the presence of elevated plasma levels of amylase and lipase and the exclusion of other causes of abdominal pain. In 80% of cases, acute pancreatitis is mild and self-limiting; the remaining 20% develop severe disease.
Full-blown acute pancreatitis is a medical emergency of the first order. Affected individuals usually experience the sudden calamitous onset of an “acute abdomen” with pain, guarding, and the ominous absence of bowel sounds. Characteristically, the pain is constant, intense and referred to the upper back; it must be differentiated from the pain of other causes such as perforated peptic ulcer, biliary colic, acute cholecystitis with rupture, and occlusion of mesenteric vessels with infarction of the bowel.
The crux of the management of acute pancreatitis is supportive therapy, e.g. maintaining blood pressure, alleviating pain and “resting” the pancreas by total restriction of oral food and fluids.
Although most individuals with acute pancreatitis eventually recover, some 5% die from shock during the first week of illness; acute respiratory distress syndrome and acute renal failure resulting from ominous complications.
Chronic pancreatitis is characterized by long-standing inflammation that leads to irreversible destruction of the exocrine pancreas. This leads eventually to loss of the islets of Langerhans. Of note, recurrent bouts of acute pancreatitis regardless of aetiology can evolve over time into chronic pancreatitis. Autoimmune pancreatitis (AIP) is a distinct form of chronic pancreatitis that is characterized by striking infiltration of the pancreas by lymphocytes and plasma cells.
By far the most common cause of chronic pancreatitis is long-term alcohol abuse. Middle-aged men constitute the bulk of patients due to obvious reasons. Still, about 40% cases of chronic pancreatitis are ‘idiopathic’ showing no recognizable predisposing factors. As with acute pancreatitis, these idiopathic cases are most likely associated with inherited mutations in genes, such as CFTR, that are important for normal pancreatic exocrine function.
Chronic pancreatitis is characterized by parenchymal fibrosis, reduced number and size of acini, and variable dilation of the pancreatic ducts. Initially, the islets of Langerhans are spared. Acinar loss is a constant feature, usually with a chronic inflammation around remaining lobules and ducts. The ductal epithelium may be atrophied. The islets of Langerhans become embedded in the sclerotic tissue and may eventually disappear. On gross evaluation, the gland is hard, sometimes with extremely dilated ducts and visible calcified concretions.
Clinical Features of Chronic Pancreatitis
Chronic pancreatitis manifests as repeated bouts of jaundice, vague indigestion, or persistent or recurrent abdominal and back pain, or it may be entirely silent until pancreatic insufficiency and diabetes mellitus develop as a consequence of islet destruction. Attacks can be precipitated by alcohol abuse, overeating, or opiates or certain drugs.
The diagnosis of chronic pancreatitis requires a high degree of clinical suspicion. A very helpful finding is the visualization of calcifications within the pancreas by CT or ultrasonography.
Chronic pancreatitis is usually not acutely life-threatening. However, the long-term outlook is poor, with a 50% mortality rate over 20 to 25 years. The most common long term effect of chronic pancreatitis is an insufficiency of pancreatic exocrine enzymes resulting in malabsorption and deficiency of fat-soluble vitamins.
The most feared long-term complication of chronic pancreatitis is pancreatic cancer. The risk for malignant transformation in adult-onset disease is modest, with no more than 5% of patients developing cancer at 20 years. In contrast, chronic pancreatitis that begins in childhood, such as hereditary pancreatitis due to PRSS1 mutations, confers a 40% to 55% lifetime risk for pancreatic cancer.
To end, pancreatic diseases can be the source of significant morbidity and mortality. Unfortunately, the retroperitoneal location of the pancreas and the generally vague nature of signs and symptoms associated with its injury or with dysfunction of the exocrine portion allow the pancreatic diseases to progress undiagnosed for extended periods of time reducing the chances of recovery.
- Acute pancreatitis is characterized by inflammation and reversible parenchymal damage that ranges from focal oedema and fat necrosis to widespread parenchymal necrosis and haemorrhage; the clinical presentation varies widely, from mild abdominal pain to rapidly fatal vascular collapse.
- Chronic pancreatitis is characterized by irreversible parenchymal damage and scar formation; clinical presentations include chronic malabsorption (due to pancreatic exocrine insufficiency) and diabetes mellitus (due to islet cell loss).
- Both entities share similar pathogenic mechanisms, and indeed recurrent acute pancreatitis can result in chronic pancreatitis. Ductal obstruction and long-term alcohol abuse are the most common causes in both forms. Inappropriate activation of pancreatic digestive enzymes (due to mutations in genes encoding trypsinogen or trypsin inhibitors) and primary acinar injury (due to toxins, infections, ischemia, or trauma) also cause pancreatitis.