48. Pancreatitis – types, etiology, pathogenesis, complications. Disorders in the gastrointestinal system: intestinal obstruction (ileus), gastro-intestinal autointoxication. Disorders in the intestinal microbiome.

Pancreatitis – types, etiology, pathogenesis, complications

• The pancreas is both an endocrine and exocrine organ
• The exocrine function involves the secretion of:

1. Proteolytic enzymes (including trypsin, chymotrypsin, carboxypolypeptidase, ribonuclease, and deoxyribonuclease) that break down dietary proteins
2. Pancreatic amylase which breaks down starch
3. Lipase which hydrolyses neutral fats into glycerol and fatty acids

• The pancreatic enzymes are secreted in the inactive form (zymogens) and become activated in the intestine otherwise the enzymes would digest the tissue of the pancreas itself if they were secreted in the active form
• Pancreatitis - an inflammatory process in which the pancreatic enzymes are auto-activated inside the pancreas and cause self-digestion of the gland

Types of pancreatitis

1. Acute pancreatitis
2. Chronic pancreatitis

1) Acute pancreatitis

• Acute pancreatitis - inflammation of the pancreas
• It ranges from a mild self-limited disease, consisting of inflammation and interstitial edema, to an acute hemorrhagic pancreatitis that is associated with massive necrosis of tissue (acute necrotising pancreatitis)

Etiology of acute pancreatitis

• Gallstones (stones in the common duct)*
• Alcohol abuse*
• Hypercalcemia
• Hyperlipidemia
• Abdominal and surgical trauma
• Vasculitis
• Viral infections
• Drugs (e.g. steroids, thiazide diuretics)

Pathogenesis of acute pancreatitis

• The initiating event may be anything that injures the acinar cells and impairs the secretion of zymogen granules e.g. alcohol abuse or gallstones

1. Gallstones/ biliary pancreatitis

• Pancreatic duct obstruction or biliary reflux is believed to activate the enzymes in the pancreatic duct system
• This damages the acinar cells and results in inflammation

1. Alcohol abuse

• At the cellular level, ethanol leads to intracellular accumulation of digestive enzymes and their premature activation and release
• At the ductal level, it increases the permeability of ductules, allowing enzymes to reach the parenchyma and cause pancreatic damage
• Ethanol increases the protein content of pancreatic juice and decreases bicarbonate levels and trypsin inhibitor concentrations
• This leads to the formation of protein plugs that block pancreatic outflow

1. Hypercalcemia

• Increased calcium concentration in pancreatic juice activates proteases
• Once a cellular injury pattern has been initiated, cellular membrane trafficking (process by which proteins and other macromolecules are distributed throughout the cell, and released to or internalised from the extracellular space) becomes chaotic, with the following deleterious effects:
• Lysosomal and zymogen granule compartments fuse, enabling activation of trypsinogen to trypsin
• Intracellular trypsin triggers the entire zymogen activation cascade
• Secretory vesicles are extruded across the basolateral membrane into the interstitium, where molecular fragments act as chemoattractants for inflammatory cells
• Activated neutrophils then exacerbate the problem by releasing superoxide (called “the respiratory burst”) or proteolytic enzymes (collagenase, elastase)