SN1 SHORT NOTE 5M ★ High-yield

Describe fatty change in the liver with its causes and mechanism.

Pathology · 2nd Professional — Para-Clinical

Definition

Fatty change (steatosis) is the abnormal accumulation of triglyceride within parenchymal cells, most often the hepatocyte.

Causes

Category	Examples
Toxins	Alcohol — by far the commonest cause; carbon tetrachloride; phosphorus
Metabolic	Diabetes mellitus; obesity — non-alcoholic fatty liver disease
Nutritional	Protein malnutrition (kwashiorkor); starvation
Hypoxia	Severe anaemia, cardiac failure
Drugs	Tetracycline, sodium valproate, amiodarone, methotrexate, corticosteroids
Pregnancy	Acute fatty liver of pregnancy
Infection	Reye syndrome; hepatitis C

Mechanism in the Liver

Normal balance — fatty acids in, triglyceride exported as VLDL → Fat may accumulate at any of five points:

→ 1.
Increased delivery of free fatty acids — starvation, diabetes, obesity → 2.
Increased fatty acid synthesis — alcohol raises NADH, favouring lipogenesis → 3.
Decreased fatty acid oxidation — alcohol, hypoxia → 4.
Increased esterification to triglyceride — alcohol raises glycerophosphate → 5.
Decreased apoprotein synthesis, so VLDL cannot be exported — carbon tetrachloride, kwashiorkor
Alcohol acts at four of the five points, which is why it is such a potent cause
Kwashiorkor acts through apoprotein deficiency — the child cannot make the protein to package the fat, so it accumulates

Morphology

Naked eye — the liver is enlarged, soft, yellow and greasy, may weigh 4–6 kg, and floats in formalin
Microscopy — clear vacuoles displacing the nucleus to the periphery; begins centrilobular and spreads outward
MACROvesicular (one large droplet) in alcohol and obesity; MICROvesicular (many small droplets with a central nucleus) in Reye syndrome, acute fatty liver of pregnancy and valproate toxicity
Fat is dissolved by routine processing, so it appears as an empty space; a frozen section with Sudan black or oil red O demonstrates it

CLINICAL PEARL

Microvesicular steatosis is the one to be frightened of. It reflects failure of mitochondrial beta-oxidation rather than simple overload, and accompanies acute liver failure with encephalopathy. Macrovesicular fat, by contrast, is usually reversible and often an incidental finding.

Applied Aspects

Fatty change is reversible — abstinence, weight loss and control of diabetes reverse it, and this is worth telling the patient plainly
The sequence in alcohol is fatty liver → alcoholic hepatitis → cirrhosis; only the first two are reversible
Non-alcoholic fatty liver disease is now the commonest liver disease, rising with obesity and type 2 diabetes in India; a proportion progresses to steatohepatitis and cirrhosis
Ultrasound shows a bright echogenic liver; the diagnosis of steatohepatitis, however, requires biopsy
Fatty change in the heart gives the "thrush-breast" appearance in severe anaemia, from alternating bands of fatty and normal myocardium

All questions in General Pathology: Cell Injury, Adaptation & Cell Death

Every Pathology chapter →