Page 54 - Textbook of Pathology, 6th Edition

38 ETIOLOGY. Fatty change in the liver may result from one From diet as chylomicrons (containing triglycerides and
of the two types of causes: phospholipids) and as free fatty acids; and
1. Conditions with excess fat (hyperlipidameia), exceeding the From adipose tissue as free fatty acids.
capacity of the liver to metabolise it. Normally, besides above two sources, a small part of
2. Liver cell damage, when fat cannot be metabolised in it. fatty acids is also synthesised from acetate in the liver cells.
Most of free fatty acid is esterified to triglycerides by the
These causes are listed below:
action of α-glycerophosphate and only a small part is
1. Conditions with excess fat: changed into cholesterol, phospholipids and ketone bodies.
i) Obesity While cholesterol, phospholipids and ketones are used in the
SECTION I
ii) Diabetes mellitus body, intracellular triglycerides are converted into
iii) Congenital hyperlipidaemia lipoproteins, which requires ‘lipid acceptor protein’.
2. Liver cell damage: Lipoproteins are released from the liver cells into circulation
i) Alcoholic liver disease (most common) as plasma lipoproteins (LDL, VLDL).
ii) Starvation In fatty liver, intracellular accumulation of triglycerides
iii) Protein calorie malnutrition can occur due to defect at one or more of the following 6
iv) Chronic illnesses (e.g. tuberculosis) steps in the normal fat metabolism shown in Fig. 3.16:
v) Acute fatty liver in late pregnancy 1. Increased entry of free fatty acids into the liver.
vi) Hypoxia (e.g. anaemia, cardiac failure) 2. Increased synthesis of fatty acids by the liver.
vii) Hepatotoxins (e.g. carbon tetrachloride, chloroform, 3. Decreased conversion of fatty acids into ketone bodies
ether, aflatoxins and other poisons) resulting in increased esterification of fatty acids to
viii) Drug-induced liver cell injury (e.g. administration of triglycerides.
methotrexate, steroids, CCl , halothane anaesthetic, 4. Increased α-glycerophosphate causing increased
4
tetracycline etc) esterification of fatty acids to triglycerides.
ix) Reye’s syndrome
5. Decreased synthesis of ‘lipid acceptor protein’ resulting
PATHOGENESIS. Mechanism of fatty liver depends upon in decreased formation of lipoprotein from triglycerides.
the stage at which the etiologic agent acts in the normal fat 6. Block in the excretion of lipoprotein from the liver into
transport and metabolism. Hence, pathogenesis of fatty liver plasma.
is best understood in the light of normal fat metabolism in In most cases of fatty liver, one of the above mechanisms
the liver (Fig. 3.16). is operating. But in the case of liver cell injury by chronic
Lipids as free acids enter the liver cell from either of the alcoholism, many factors are implicated which includes:
General Pathology and Basic Techniques
following 2 sources: increased lipolysis;
increased free fatty acid synthesis;
decreased triglyceride utilisation;
decreased fatty acid oxidation to ketone bodies; and
block in lipoprotein excretion.
Even a severe form of liver cell dysfunction may be
reversible; e.g. an alcoholic who has not developed
progressive fibrosis in the form of cirrhosis, the enlarged fatty
liver may return to normal if the person becomes teetotaller.

MORPHOLOGIC FEATURES. Grossly, the liver in fatty
change is enlarged with a tense, glistening capsule and
rounded margins. The cut surface bulges slightly and is
pale-yellow to yellow and is greasy to touch (Fig. 3.17).
Microscopically, characteristic feature is the presence of
numerous lipid vacuoles in the cytoplasm of hepatocytes.
Fat in H & E stained section prepared by paraffin-
embedding technique appear non-staining vauloes
because it is dissolved in alcohol (Fig. 3.18):
i) The vacuoles are initially small and are present around
the nucleus (microvesicular).
ii) But with progression of the process, the vacuoles
become larger pushing the nucleus to the periphery of
the cells (macrovesicular).
iii) At times, the hepatocytes laden with large lipid
Figure 3.16 Lipid metabolism in the pathogenesis of fatty liver. vacuoles may rupture and lipid vacuoles coalesce to form
Defects in any of the six numbered steps (corresponding to the description fatty cysts.
in the text) can produce fatty liver by different etiologic agents.