Question

A 53-year-old male with past medical history of obesity (BMI of 38 kg/m 2 ) and borderline diabetes presents to you with abnormal liver enzymes (ALT/AST) discovered 6 months ago. His family history is significant for liver cirrhosis. On physical examination you notice mild hepatomegaly (enlarged liver). A panel of lab tests revealed the following: aspartate aminotransferase (AST) 106 (normal range 10 – 40 U/L), alanine aminotransferase (ALT) 118 (normal range 7 – 56 U/L), with normal bilirubin (generated from the breakdown of hemoglobin). He had a liver ultrasonography that showed diffuse increase in echogenicity and vascular blurring consistent with fatty infiltration. You suspect nonalcoholic fatty liver disease (NAFLD). Under normal conditions, describe the metabolism and maturation of VLDL particles. Describe how NAFLD could manifest and what potential processes could be impaired in order for this disease process to occur (consider both enzymatic and hormonal impairments).

Answer 1

SOLUTION:-

MATURATION OF VLDL PARTICLES:-

The liver synthesizes nascent VLDL containing apo B100 which are rich in tricyglycerols and cholestrol .

Circulating HDL donates apo C and apo E to covert nascent VLDL to VLDL.

  METABOLISM OF VLDL PARTICLES?:-

  The enzyme lipoprotein lipase is present in many tissues of the body such as capillary walls of adipose tissue, cardiac and skeletal muscle. It hydrolyzes a portion of triacylglycerols present in VLDL to liberate free fatty acids and glycerol. this enzyme is activated by apo C.

As the triacylglycerols of VLDL are degraded , they lose the apo C which is returned to HDL. During the course of VLDL metabolism ,IDL The is formed which lose apo E and get converted to LDL. The apo E is also returned to HDL.

  MANIFESTATION:-

Individuals are generally asymptomatic when present with simple steatosis. In about 80% of cases there is no progression to cirrhosis. There are generally clinical presentation to metobolic syndrome such as diabetes mellitus. Right sided abdominal discomfort may be caused by hepatomegaly.

NAFLD are mostly associated with metabolic syndrome , obesity, type 2 diabetesmellitus, hypertension and dyslipide,ia.

  Insulin resistance causes hepatic steatosis.

The hepatocellular oxidative injury results in hepatic necrosis and also causes inflammatory reactions to it.

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