Chronic pancreatitis

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Chronic pancreatitis

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A 58-year-old woman with a history of chronic alcohol use disorder comes to the office because of diarrhea, generalized weakness, and a 6.8-kg (15-lb) weight loss over the past 6 months. She reports intermittent dull upper abdominal pain that will last for days at a time and is not improved with antacids. After meals, she feels that her abdomen is distended. She characterizes her multiple daily bowel movements as greasy, foul-smelling, and oily. She recently was the driver involved in a minor traffic accident, which she attributes to worsening eyesight at night. Her temperature is 37.0°C (98.6°F), pulse is 78/min, respirations are 16/min, and blood pressure is 135/85 mmHg. Abdominal examination shows resonance to percussion throughout and a mildly tender epigastrium. Bowel sounds are hyperactive. Laboratory values show the following:  
 
 Laboratory value  Result 
 Calcium, serum  7.6 mg/dL 
 Partial thromboplastin time  60 seconds 
 Prothrombin time  28 seconds 

Which of the following is the most likely etiology of this patient's diarrhea?

External References

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CFTR gene p. 58

chronic pancreatitis and p. 404

Chronic pancreatitis p. 404

pancreatic insufficiency from p. 388

Steatorrhea

chronic pancreatitis p. 404

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Chronic pancreatitis is persistent, chronic inflammation of the pancreas often due to repeated bouts of acute pancreatitis.

While a history of acute pancreatitis might lead to chronic pancreatitis these diseases have distinct histopathologies.

Acute pancreatitis is inflammation caused by destruction of the pancreas by its own digestive enzymes—a process called autodigestion, and is generally reversible.

Chronic pancreatitis is inflammation due to irreversible changes to the pancreatic structure, like fibrosis, atrophy and calcification.

The pancreas is a long, skinny gland the length of a dollar bill and is located in the upper abdomen, or the epigastric region, behind the stomach. It plays endocrine roles—for example, alpha and beta cells make hormones like insulin and glucagon that are secreted into the bloodstream, but it also plays exocrine roles— for example, acinar cells make digestive enzymes that are secreted into the duodenum to help digest food.

These pancreatic digestive enzymes break down macromolecules like carbohydrates, lipids and proteins found in food, but these macromolecules are also found in the cells of the pancreas.

To protect the pancreas, the acinar cells manufacture inactive forms of the enzymes called proenzymes, or zymogens.

These zymogens are normally activated by proteases which cleave off a polypeptide chain, which is kind of like pulling the pin on a grenade.

For additional security, the zymogens are kept away from sensitive tissues in storage vesicles called zymogen granules, and are packaged with protease inhibitors that prevent enzymes from doing damage if they become prematurely active.

To digest a meal, these zymogens are released into the pancreatic duct, and delivered to the small intestine where they are activated by the protease trypsin.

Trypsin is a pancreatic digestive enzyme that is produced as the zymogen trypsinogen.

Normally, trypsinogen isn’t activated until it is cleaved by protease enteropeptidase which is found in the duodenum.

But if trypsinogen and these zymogens become activated too early, then it can cause acute pancreatitis, and this might happen as a result of any injury to the acinar cells, or anything that prevents the normal secretion of the proenzymes into the duodenum.

Fuentes

  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  3. "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
  4. "CURRENT Medical Diagnosis and Treatment 2020" McGraw-Hill Education / Medical (2019)
  5. "Spectrum of Causes of Pancreatic Calcifications" American Journal of Roentgenology (2002)
  6. "Smoking and Risk of Acute and Chronic Pancreatitis Among Women and Men" Archives of Internal Medicine (2009)