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Explain how insulin resistance can lead to the development of hepatic steatosis
skeletal resistance -> glucose to liver; adipose resistance -> lipolysis = glycerol + Fatty acids -> fats deposited in liver
Explain how hepatocellular oxidative injury can result in hepatic inflammation and necrosis
Reactive oxygen species produced in mitochondria + ER of hepatocytes via cytochrome P450-> imbalance oxidants/antioxidants=structural & functional abnormality
Identify common comorbidities of NAFLD
hepatic manifestation of metabolic syndrome linked with insulin resistance; obesity, dyslipidemia, diabetes
Identify the spectrum of disorders of NAFLD
NAFD --> NASH --> Fibrosis --> Cirrhosis
Elaborate the role of statin in the regulation of intracellular cholesterol synthesis
Statins inhibit HMG-CoA reductase->reduce cellular cholesterol synthesis->Lower intracellular cholesterol->over-expression of the LDL receptors=lower plasma LDL
Describe the therapeutic benefits and potential adverse effects associated with HMG-CoA reductase inhibitors
Pleiotropic effects: NO synthesis, LDL lower, Inflammatory down; Adverse: myopathy; decrease Coenzyme Q10 -> impair energy in muscles = myalgia
Explain the pathogenesis of dyslipidemia
Primary: Genetic - over production/defective LDL or over-clearance HDL; Secondary: lifestyle + other factors -high free fatty acids + high VLDL =excessive fats
Describe specific dietary modifications and medicinal foods (soy, green tea, flax, olive oil) for dyslipidemia.
soy-reduces HMG-CoA reductase; Green Tea Extract and Green Tea-reduces FA gene expression, inhibits HMG-CoA reductase; flax-reduce LDL
Explain the pathogenesis of hepatitis C virus
human reservoir→transmission by blood, semen, in utero→infects hepatocytes→immune response by CTLs kills infected hepatocytes=acute hepatitis
Explain the rationale for utilizing sofosbuvir-velpatasvir in previously untreated hepatitis C
Velpatasvir: NS5A inhibitor; Sofosbuvir: NS5B polymerase inhibitor; both work by weakening the activity of proteins needed by hepatitis C
Discuss the Batts-Ludwig grading and staging criteria
Grade-amount of necroinflammatory activity; Stage-amount of fibrosis
Define shifting dullness, palmar erythema, and asterixis (reference: Alcoholic Cirrhosis Physical Exam)
shifting dullness: ascites sign, Percuss across abdomen-transition tympany to dull; palmar erythema: red palms from oestradiol; asterixis: negative myoclonus
Describe life-threatening complications from cirrhosis including hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP), and esophageal varices (EV)
HE: toxin build up in blood->brain damage; SBP: infection of ascitic fluid in peritoneum; EV: blood flow to liver blocked->enlarged esophageal veins
Explain the use of osmotic laxatives (lactulose) to manage hepatic encephalopathy.
colonic acidifier that works by decreasing the amount of ammonia in the blood (decrease intestinal production/absorption of ammonia) -> less toxin to brain
Describe the immunologic mechanisms resulting in hepatic injury from hepatitis
immune system–mediated cytotoxicity: (HLA) class I–restricted CD8 CTL's recognize hepatitis B core antigen + e antigen on infected hepatocytes->inflammation
In celiac disease, explain how malabsorption can result in osmotic diarrhea
damaged villi + mucosa --> Osmotic diarrhea=osmotically active, poorly absorbed solutes in the bowel lumen->inhibit normal water + electrolyte absorption
