SEARCH RESULTS FOR: alcoholic-fatty-liver-disease-pathogenesis-and-clinical-findings

alcoholic-fatty-liver-disease-pathogenesis-and-clinical-findings

Alcoholic Fatty Liver Disease: Pathogenesis and clinical findings Authors: Tara Shannon Reviewers: Ben Campbell, Yan Yu*, Samuel Lee* * MD at time of publication ↑NADH:NAD+ ratio in hepatic cells, a “high energy state” marker in the cell When a cell is in a high energy state, metabolic processes that provide energy are inhibited ↓ β-oxidation (break down) of triglycerides in the liver Abbreviations: • CYP2E1 – Cytochrome P450, subtype 2E1 • NADH/NAD+ – Nicotinamide Adenine Dinucleotide (in reduced and oxidized form respectively) Ethanol upregulates hepatic cell fatty acid transporters such as fatty acid transport protein 1 and 5 (FATP1,5) ↑ Fatty acid transporters in hepatic cells ↑ Uptake of free fatty acids from circulation into hepatic cells Alcohol (ethanol) consumption Ethanol is primarily metabolized in the liver by enzymes alcohol dehydrogenase (ADH) and CYP2E1 ADH converts ethanol into acetaldehyde & NADH CYP2E1 converts ethanol into acetaldehyde Excessive alcohol consumedàthe liver cannot process ethanol and its metabolites quickly enoughà ethanol, acetaldehyde, and NADH accumulate in the liver and may enter the bloodstream Acetaldehyde is a highly reactive and unstable molecule that can damage proteins, enzymes, and DNA (Hepatic stellate cells (HSC) are sensitive to liver damage and release cytokines when activated) Acetaldehyde activates HSCàHSC release tumor necrosis factor alpha (TNF-!), an inflammatory markerà↑ liver inflammation Acetaldehyde upregulates the production of enzymes required for fatty acid synthesis TNF-! stimulates fat production in liver cells TNF-! enters circulation and stimulates adipose cells to break down, releasing triglyceride stores as free fatty acids ↑ Free fatty acids released into circulation Liver biopsy shows liver inflammation TNF-! causes the production of reactive oxygen species (unstable, highly reactive molecules) Reactive oxygen species cause oxidative damage to hepatic cells’ mitochondria Damaged mitochondria can no longer efficiently perform metabolic tasks ↑ Building blocks, catalysts, and direct stimulating factorsàliver cells ↑ fat production ↑ Lipogenesis in the liver (triglyceride production) ↑ Triglyceride accumulation in liver cells Triglyceride-rich droplets in hepatic cells change the cells’ physical properties compared to normal liver cells, allowing imaging modalities to exploit these differences to detect lipid infiltration Fatty livers appear darker on CT scans Liver biopsy shows triglyceride- rich droplets inside liver cells Fatty livers appear brighter and with poorer visualization of structures (like bile ducts and vessels) on ultrasounds Imaging such as ultrasound, CT, and MRI can visualize and quantify liver fat Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 21, 2022 on www.thecalgaryguide.com