Liver Flashcards
What is NAFLD?
Non-alcoholic fatty liver disease
Altered insulin: glucagon ratio promotes de novo lipogenesis (conversion of excess nutrients into fatty acids), glycogenolysis and gluconeogenesis in live–> increasing hepatic glucose production and hepatic insulin resistance
Several hormones secreted by the GI tract regulate glucose/ lipid metabolism as well as food intake and thus might be implicated in NAFLD development
Imparied GLP1-secetion and decreased GLP-1 receptors have been reported in those with NAFLD further impairing glucose and lipid metabolism.
Symptoms of NAFLD
Usually asymptomatic
- Pain –> upper right part of the abdomen
- Fatigue –> circulating toxins
- Jaundice –> cant process bilirubin from red blood cells
- Oedema –> legs and abdomen, usually later stages
How is NAFLD diagnosed?
Blood test
- elevated liver enzymes
- viral serology to exclude hep B
Assess alcohol intake –> less than 2 a day
- imaging study –> showing fatty infiltrate –> ultrasound, MRI
- liver biopsy
NAFLD diagnosis
Also can diagnose by calculating fatty liver index and lipid accumulation product.
Fatty liver index –> BMI, waist circumference, triglycerides and GGT
Lipid accumulation product –> waist circumference and fasting triglycerides
How are transaminases used in the diagnosis of NAFLD?
Transaminases synthesis and break down amino acids and to convert energy storage molecules.
ALT –> aspartate aminotransferase
AST –> alanine aminotransferase
ALT is found in the liver only
AST in cardiac and skeletal muscle
Elevated levels are indications of liver injury
The hepatocyte cell membrane becomes more permeable and some of the enzyme leak into the circulation
MORE ALT than AST = NAFLD
Discuss NAFLD and obesity
Increased intrahepatic triglyceride is associated with peripheral insulin resistance
FA accumulate in liver to be processed to Fatty acetyl-CoA to enter krebs cycle in mitochondria
Mitochondiral dysfunction decreases ability to oxidise Acetyl-CoA so have less capacity to oxidise fat.
Ceramide is produced instead and with accumulation can down-regulate proteins that are used by insulin. The downregulation is a contributor to insulin resistance as it is being prevented from carrying out its function.