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This is a mechanism of disease flowchart for cholelithiasis, cholecystitis, and other associated complications, covering the etiologies, pathophysiologies, and manifestations of these conditions. ADDITIONAL TAGS: Forty (40) years of age Obstruction / mass effect Signs / symptoms Labs / tests / imaging results Cholelithiasis, Cholecystitis Core concepts Social determinants of health / risk factors Pharmacology / toxicity Microbial pathogenesis Biochem / organic chem Flow gradients Genetics / hereditary Inflammation Pathophysiology Etiology Manifestations Passage of gallstones into the cystic duct Cystic duct obstruction Distension of gallbladder Inflammation: release of cytokines / mediators that initiate a reaction +/- bowel pathogens (E. coli, Klebsiella, Enterobacter, Enterococcus) infiltrate the bile ducts Local bacterial infection RUQ pain -More severe, prolonged (6hrs) than biliary colic -Fatty meal → gallbladder contracts to release bile into the duodenum to aid in digestion by emulsifying fats → postprandial pain Irritates phrenic nerve Pain radiates to right scapula Inspiration → gallbladder pushed caudally Positive Murphy sign: sudden pause during inspiration w deep palpation of RUQ Guarding Fever Anorexia, malaise Nausea, vomiting Complications -Ischemic necrosis → gangrenous cholecystitis Ischemic necrosis → break in gallbladder wall → perforation → biliary peritonitis +/ hemorrhagic cholecystitis -Cholelithiasis → chronic irritation → recurrent but self-limiting acute cholecystitis → chronic cholecystitis → gallbladder cancer, porcelain gallbladder, cholecystoenteric fistula → gallstone ileus -Bacterial infiltration → gallbladder empyema (suppurative cholecystitis) -Bacterial infiltration → pericholecystic, pyogenic liver, or subhepatic abscess Formation of chole- sterol stones (95%) Abnormal hepatic cholesterol metabolism ↑ cholesterol in bile + ↓ bile salts → hypersaturated bile Cholesterol and calcium carbonate precipitate Fat: obesity, insulin resistance, dyslipidemia ↑ estrogen Female sex Fertile (pregnant or multiparity) ↑ progesterone Biliary stasis Smooth muscle relaxation ↓ gallbladder contraction Fair-skin: European, Hispanic, Native Amer. Family history Fibrates (inhibit cholesterol 7-α hydroxylase) Estrogen therapy; OCPs Malabsorption (Crohn, ileal resection, CF) Formation of black pigment stones (10%) Bilirubin polymers precipitate ↑ uptake, ↑ conjugation of bilirubin ↑ circulating unconjugated bilirubin SCD; hereditary spherocytosis ↑ hemolysis Alcoholic cirrhosis Total parenteral nutrition Formation of mixed / brown pigment stones (10%) calcium carbonate, cholesterol, and calcium bilirubinate precipitate ↑ unconj. bili and ↑ fatty acids Infection of the biliary tract (gut bacteria, Clonorchis sinensis, Opisthorchis species) Bacteria and injured hepatocytes release β-glucuronidase Hydrolysis and conjugation of bilirubin in bile Reduced perfusion of gallbladder → acute acalculous cholecystitis Critical illness (surgery, trauma, burns, multiorgan failure, infxn → septic shock, TPN, immunodeficiency) Gas-forming bacteria (Clostridium spp., E.coli) → emphysematous cholecystitis → air within gallbladder wall/lumen RUQ u/s: GB wall thick (3 mm), wall edema, GB distention (40 mm), pericholecystic and perihepatic (C sign) fluid