Acute and chronic pancreatitis Year 4 Internal Medicine Notes

Acute and chronic pancreatitis Year 4 · Internal Medicine Collection: 4TH YEAR ALL NOTES / IMED / IMED 4.1 / ALEX -- Slide 1 Acute and chronic pancreatitis Dr. Alex Mogere Consultant Physician Slide 2 outline Anatomy Definition Aetiology Mechanism of disease Presentation Diagnosis Management Slide 3 Anatomy Retroperitoneal structure, 10–15 cm long, lying across the upper lumbar spine. Extends from the duodenal loop (head)to the hilum of the spleen (tail). Its close proximity to a number of intra-abdominal structures, gives rise to the possibility of a number of local complications of pancreatic inflammation. Major digestive organ of the body. Secretes up to 20 g of enzyme protein into the duodenum each day. synthetic capacity of proteins similar to that of the lactating mammary gland. Slide 4 Defn Pancreatitis is a necro-inflammatory condition of the pancreas. arises as a result of inappropriate activation of digestive enzymes within the gland. Acute pancreatitis is generally a mild, self-limiting disease, requiring only conservative medical therapy. A minority of cases are severe, with local and/or systemic complications and significant mortality (10%–30%). Slide 5 Acute pancreatitis: aetiologic associations Common Gallstones Uncommon Hypertriglyceridaemia Hyperparathyroidism Surgery Endoscopic pancreatography Trauma Drugs: azathioprine, thiazide diuretics, oestrogens, furosemide, sulfonamides, tetracyclines, valproic acid, pentamidine Infections: mumps, viral hepatitis, coxsackie, echo virus, ascariasis,mycoplasma Vasculitis Obstruction of ampulla of Vater Penetrating peptic ulcer Slide 6 pathogenesis Duct obstruction→Blockage of Exocytosis of zymogen granules from pancreatic acinar cells → zymogen granules coalesce with lysosomes within the acinar cell to form autophagic vacuoles → lysosomal enzymes activate digestive enzymes → autodigestion of the gland. Cell injury and death give rise to an inflammatory response, with local release of pro-inflammatory cytokines and other inflammatory mediators. severe inflammatory response → multiorgan failure & local complications Slide 7 : Gallstones may intermittently migrate out of the gallbladder (GB) via the cystic duct (CD) into the common bile duct (CBD) and then pass through the choledochoduodenal junction (CDJ) into the duodenum (D). B: Gallstones cause transient obstruction of the pancreatic duct (PD) as they pass from the CBD through the CDJ into the duodenum. Obstruction of the PD raises hydrostatic pressure within it, causing blockage of pancreatic secretion and subsequent activation of pancreatic enzymes within the pancreas. This is thought to be the initiating factor in gallstone pancreatitis. Gallstones may also become impacted at the CDJ, causing a persistent obstruction. Mechanism of gall stone Pancreatitis Slide 8 Mech. of alcoholic pancreatitis Alcohol, its metabolites and oxidant stress exert a number of toxic effects on pancreatic acinar cells, which predispose the gland to autodigestive injury, acute necro-inflammation and cell death. These include: 1: destabilisation of lysosomes (L) and zymogen granules (ZG) (mediated by oxidant stress [reactive oxygen species; ROS], cholesteryl esters [CE], fatty acid ethyl esters [FAEE] and decreased glycoprotein 2 [GP2], a major structural component of zymogen membranes); 2: increased digestive and lysosomal enzyme content (due to increased synthesis [increased mRNA] and impaired secretion); 3: increased activation of transcription factors (NFkB and AP-1) which regulate cytokine expression; 4: a sustained increase in cytoplasmic calcium (Ca++) and mitochondrial calcium overload leading to mitochondrial depolarisation. The above changes sensitise the cell such that in the presence of an appropriate trigger or cofactor, injury is initiated. Slide 9 Possible susceptibility factors in alcoholic pancreatitis inherited factors Lifestyle factors HLA Diet α1-antitrypsin deficiency Beverage type Cystic fibrosis genotype Alcohol metabolising enzymes Drinking pattern Alcohol dehydrogenase Smoking Cytochrome P450-2E1 Cholesteryl ester lipase Trypsinogen gene mutations PSTI/SPINK1 mutations Cytokines Detoxifying enzymes Glutathione S-transferase UDP-glucuronosyl transferase Slide 10 Clinicial features Acute pancreatitis Major symptom is severe, constant abdominal pain. usually epigastric or peri-umbilical. It may radiate to the back and into the chest or flank. Often, pain is relieved by sitting forward and exacerbated by lying flat. pain is often associated with nausea and vomiting. Slide 11 p/e Gc is sick looking, dehydratated,+/- Pyrexia, tachycardia PA: tenderness, guarding, distension, ileus signs of pulmonary decompensation may be present and may be harbingers of severe pancreatitis. Cullen’s sign (blue discolouration around the umbilicus) Grey-Turner’s sign (purple discolouration in the flanks) rarely seen, but indicate severe necrotising pancreatitis Slide 12 Ddx Slide 13 diagnosis presence of two of the followi