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
10
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
10
Identify common comorbidities of NAFLD
hepatic manifestation of metabolic syndrome linked with insulin resistance; obesity, dyslipidemia, diabetes
10
Identify the spectrum of disorders of NAFLD
NAFD --> NASH --> Fibrosis --> Cirrhosis
10
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
10
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
10
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
10
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
10
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
10
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
10
Discuss the Batts-Ludwig grading and staging criteria
Grade-amount of necroinflammatory activity; Stage-amount of fibrosis
shifting dullness: ascites sign, Percuss across abdomen-transition tympany to dull; palmar erythema: red palms from oestradiol; asterixis: negative myoclonus
10
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
10
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
10
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
10
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