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Kurs: MCAT > Rozdział 2

Lekcja 1: Biological sciences practice passage questions

The role of alcohol abuse in pancreatitis


The exocrine component of the pancreas is an integral part of the digestive system. Though not a segment of the gastrointestinal (GI) tract itself, the pancreas is a major producer of enzymes necessary for the chemical digestion of food. These enzymes are synthesized in their zymogen forms and then sent to the small intestine where they are activated.
When pancreatic enzymes are activated before reaching the small intestine, they start to attack the pancreas itself, leading to inflammation, known as pancreatitis. Acute pancreatitis is a temporary condition, with about 80% of patients recovering completely. However, prolonged exposure to these enzymes will lead to irreversible cell death and chronic inflammation. This is called chronic pancreatitis, and it has been linked to pancreatic cancer and organ failure.
The leading cause of pancreatitis is alcohol abuse – the excessive consumption of alcohol over a prolonged period of time. Scientists are still trying to understand the development of the disease, and recently research focus has shifted to the acinar cells of the pancreas – the cells that produce the aforementioned pancreatic enzymes. The prevalent theory, illustrated in Figure 1, holds that byproducts of ethanol digestion weaken lysosomes (L) and zymogen granules (ZG) inside the acinar cell. When the contents of these organelles meet, pancreatic enzymes are activated. The presence of ethanol also leads to increased production of digestive enzymes.
Figure 1. Hypothetical development of alcoholic pancreatitis in acinar cells. Ethanol metabolites destabilize lysosomes (L) and zymogen granules (ZG), and trigger increased transcription of pancreatic enzymes.
As enzyme content increases and the barriers separating them weaken, it is more and more likely that the digestive juices meant for the small intestine activate in the acinar cells instead. This early enzyme activation begins a chain of events that eventually activates pancreatic stellate cells (PSCs). These PSCs are responsible for producing extracellular matrix – when activated in excess they can lead to the pancreatic fibrosis and permanent pancreatic damage characteristic of chronic pancreatitis.
A major piece of support for this theory is the effect that alcohol and its metabolites have on fibrogenesis in PSCs. In a study conducted in 2000, rat PSCs were isolated and treated with ethanol and acetaldehyde, a product of ethanol oxidation. Each compound led to a significant increase in the production of collagen by the pancreatic cells.
Figure 2: Effects of ethanol and acetaldehyde on collagen synthesis in pancreatic stellate cells. Ethanol was added at concentrations of 10mmol/L(E10) and 50mmol/L (E50). Acetaldehyde was added at concentrations of 150μmol/L (A150) and 200μmol/L (A200) to cell preparations.
Data adapted from:
Apte, M. (2000). Does alcohol directly stimulate pancreatic fibrogenesis? Studies with rat pancreatic stellate cells. Gastroenterology, 780-794.
Vonlaufen, A. (2007). Role of alcohol metabolism in chronic pancreatitis. Alcohol Res Health, 48-54.
What is the main mechanism that normally prevents pancreatic enzymes from being activated before they reach the small intestine?
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