Last updated on April 30, 2020 at 23:28
The exocrine part of the pancreas accounts for 99% of the organ. The exocrine pancreas is composed of ductules, ducts and acinar cells that produce digestive enzymes. These enzymes are secreted in pro-enzyme form inside zymogen granules, so that they aren’t activated before they reach the lumen of the duodenum. The enzymes include trypsin, phospholipase, elastase and lipase.
The pancreas has multiple mechanisms to prevent premature activation of the digestive enzymes:
- They are synthesized as inactive proenzymes
- Their activation requires conversion of trypsinogen to trypsin by duodenal enteropeptidase
- The acinar cells also secrete trypsin inhibitors
- The acinar cells are very resistant to the digestive effects of the activated digestive enzymes
- Trypsin cleaves and inactivates itself as a negative feedback mechanism.
Autodigestion of the pancreas occurs when these enzymes are prematurely activated in the pancreas. This process is the background of pancreatitis.
Acute pancreatitis is a reversible inflammatory disorder that varies in intensity from just oedema and adiponecrosis to widespread parenchymal necrosis. It occurs when something causes the digestive enzymes to be activated before they reach the duodenum. These digestive enzymes digest the pancreas. The disease has a high mortality, around 10-15%.
Etiology: Acronym GET SMASHED
- Ethanol (Alcoholism)
- Mumps (and Coxsackie) Virus
- Scorpion venom
- Hypercalcaemia, Hyperlipidemia
Other causes are Vascular (shock, arteroembolism, polyarteritis nodosa), mutations (PRSS1, SPINK1), Idiopatic, etc
The most common causes are alcoholism and gallstones in the biliary tract distal to the pancreatic duct. These two factors are responsible for 80% of all cases of acute pancreatitis.
Pathomechanism: Alcohol increases the viscosity of the pancreatic juice while also increasing the tone of the sphincter of Oddi. This decreases the outflow of the pancreatic juice, which increases the risk that the enzymes will be activated inside the pancreas. Gallstones stuck in the biliary tract distal to the pancreatic duct block outflow of the pancreatic juice.
Pathomechanism: As the digestive enzymes are activated will elastase start to digest the vasculature. This causes leakage of fluid into the parenchyme, causing oedema. Further digestion of vessels causes interstitial haemorrhage.
Digestive enzymes destroy the pancreatic parenchyme and causes necrosis. As the enzymes reach the intrapancreatic and peripancreatic fat will the pancreatic lipases digest the triacylglycerols inside the adipocytes. This forms free fatty acids that will combine with calcium to form soap. This process is adiponecrosis. As the disease progresses may mesenterial and subcutaneous fat also be digested.
The severe necrosis recruits inflammatory cells, causing an acute inflammation.
The basic alterations in acute pancreatitis can therefore be summarized as (1) Microvascular leakage causing oedema, (2) Proteolytic destruction of pancreatic parenchyma, (3) Adiponecrosis, (4) Acute inflammatory reaction and (5) interstitial hemorraghe.
Types: We distinguish two forms of acute pancreatitis. The less severe one is oedematous acute pancreatitis, where there is oedema and adiponecrosis but no haemorrhage. The more severe form is haemorrhagic acute pancreatitis, where there is also haemorrhage.
Pseudocysts: Acute pancreatitis may result in a pancreatic pseudocyst. The pseudocyst is formed when liquefied areas of necrotic pancreatic tissue becomes walled off by fibrous tissue. It’s not a true cyst as epithelium doesn’t line the cyst. These cysts may resolve themselves, become infected or compress adjacent structures.
Diagnosis: Elevated pancreatic enzymes, especially lipase and amylase suggest acute pancreatitis. CT and ultrasound are also useful.
Symptoms: Patients usually have severe pain in the upper abdomen which radiates to the back. Nausea and vomiting are also common.
Treatment: Treatment is mostly supportive. Giving fluid is important to prevent development of shock. Denying oral feeding is important to prevent stimulating more pancreatic secretions.
Chronic pancreatitis is similar to the acute type in that autodigestion of the pancreas occurs. It can occur due to repeated bouts of acute pancreatitis. It can also be primary and occur due to many of the same causes as for acute pancreatitis. A major difference between acute and chronic type is that the latter involves replacement of the normal pancreatic parenchyme by scar tissue. The parenchymal injury in the chronic type is irreversible.
- Alcohol abuse
- Cystic fibrosis
Symptoms: Epigastric abdominal pain radiating to the back is common here as well. Nausea and vomiting too.
Complications: Chronic pancreatitis may lead to chronic malabsorption due to the loss of exocrine pancreas function, or diabetes mellitus due to loss of endocrine pancreas function.
Neoplasms of the pancreas may originate from the endocrine cells or the exocrine cells. Neuroendocrine tumors like gastrinomas or insulinomas originate from the cells of the Langerhans islets.
The exocrine neoplasms may be either cystic or solid. Some of these are benign and some are among the most lethal of all malignancies.
The cystic neoplasms are:
- Serous cystadenomas
- Mucinous cystadenomas
- Intraductal papillary mucinous neoplasms
The solid neoplasms are:
- Solid pseudopapillary neoplasm/solid papillary cystic neoplasia
- Pancreatic adenocarcinoma
Serous cystadenomas are the most common cystic neoplasm of the pancreas. They occur most frequently in older and female patients. They are almost always benign. They’re associated with mutations in the VHL tumor suppressor gene.
Mucinous cystadenomas are almost exclusively found in women are usually found in the body or tail of the pancreas. The cysts are filled with thick mucin. Up to one third of these neoplasms have dysplasia and therefore can become malignant.
Intraductal papillary mucinous neoplasms (IPMN) (or intraductal papillary cystic neoplasm according to the lecture) grow in the larger ducts of the pancreas. These neoplasms are more common in males than in females. Up to two thirds of these neoplasms have mutations that give them the possibility to turn malignant.
Solid pseudopapillary neoplasm is a low grade malignant epithelial tumor that is usually found in the body or tail. Mainly young females are affected. This tumor is locally aggressive.
Pancreatic adenocarcinoma is what’s commonly referred to as “pancreatic cancer”. It has one of the highest mortality rates of all cancers. 60% of cases are located in the head of the pancreas, with the remaining 40% being spread evenly throughout the body and tail. People in their 60s – 80s are most commonly affected.
- Chronic pancreatitis
Symptoms: Those cases where the tumor in the head have the best prognosis, simply because they cause symptoms first and are therefore the first to be discovered. Tumors of the body and tail produce symptoms very late and are therefore often not found until the late stage. Common symptoms include:
- Posthepatic (obstructive) jaundice
- Courvoisier’s sign – enlarged but nontender gallbladder that is palpable
- Trousseau’s sign – recurring thrombophlebitis (blood clots)
Prognosis: Pancreatic adenocarcinoma is very aggressive. Metastases are often present upon diagnosis. It frequently invades local structures and can even invade the portal vein itself. If the tumor invades other structures locally is it frequently considered inoperable. The 5-year survival rate is less than 5%.
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