Page 453 - Concise Pathology for Exam Preparation ( PDFDrive )

438 SECTION II Diseases of Organ Systems

Q. Write briefly on nonalcoholic fatty liver disease (NAFLD).

Ans. NAFLD is a group of disorders which resemble alcoholic steatohepatitis but occurs
in the absence of alcohol intake.
• Important risk factors for development of this entity are obesity, Type II diabetes melli-
tus and hyperlipidaemia (metabolic syndrome*). Insulin resistance increases lipid ac-
cumulation (steatosis). The lipid so formed is dysfunctional leading to decreased pro-
duction of the lipid hormone ‘adiponectin’ with a simultaneous increase in inflammatory
cytokines like IL-6 and TNF-a. This predisposes the fat-laden hepatocytes to apoptosis
and oxidative injury, which in turn is responsible for hepatocellular necrosis and associ-
ated inflammation.
• NAFLD is a common incidentally discovered cause for abnormal liver tests (once other
causes of liver diseases are excluded).
• NAFLD is broadly divided into two groups:
(a) Patients with isolated fatty liver disease (80%): These patients are asymptomatic at
the time of diagnosis; some have fatigue, malaise and hepatomegaly. They show
none or minimal progression to cirrhosis.
(b) Patients with nonalcoholic steatohepatitis or NASH (20%): NASH shows a histology
identical and to alcoholic hepatitis. Patients with NASH have a much higher pro-
pensity to progress to cirrhosis and hepatocellular carcinoma. NASH is a significant
contributor to the group ‘cryptogenic cirrhosis’.

Q. Write briefly on the aetiology and clinicopathological features
of haemochromatosis.

Ans. Haemochromatosis is a condition in which there is excessive iron absorption leading
to parenchymal iron overload. It may be hereditary or acquired in nature.
1. Hereditary haemochromatosis
Occurs due to mutations in genes encoding for proteins regulating hepcidin levels, eg,
haemochromatosis gene (HFE gene; located on chromosome 6), transferrin receptor
(TFR) 2 gene and haemojuvenile (JJV) gene or the hepcidin gene itself. Hepcidin, a
hepatocellular protein which has bactericidal activities, is the main regulator of iron
absorption and is encoded by HAMP gene. It lowers plasma iron levels and a muta-
tion in either hepcidin gene itself or the genes encoding for the regulatory proteins
result in iron overload.

Aetiology
• Mutations in HFE gene and TFR 2 gene lead to the classic adult form of hereditary
haemochromatosis.
• Mutations in the HAMP gene or HJV lead to a severe form of hereditary haemochroma-
tosis called neonatal haemochromatosis.

*Source: WHO criteria for defining metabolic syndrome:
Any one of the following:
- Diabetes mellitus or
- Impaired glucose tolerance or
- Impaired fasting glucose or
- Insulin resistance
And two of the following:
- Blood pressure . 140/90 mm Hg
- Dyslipidaemia (Triglycerides . 169.5; HDL cholesterol , 0.9 mmol/L in males and , 1 mmol/L in females)
2
- Central obesity (waist–hip ratio . 0.90 in males and . 0.85 in females or body mass index . 30 kg/m )
- Microalbuminuria (urinary albumin . 20 mcg/min and albumin/creatinine ratio . 30 mg/gm)

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