Avian Pathology

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Fatty liver diseases in the domestic fowl — A

review

E.J. Butler

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Avian Pathology, 5: 1-14, 1976

FATTY LIVER DISEASES IN THE DOMESTIC FOWL

A REVIEW

E.J. BUTLER
Houghton Poultry Research Station
Huntingdon, Cambs., England

SUMMARY
The metabolic disorders known as fatty liver and kidney syndrome and
fatty liver-haemorrhagic syndrome are described, and their pathogenesis
and aetiology are discussed in relation to current knowledge of the lipid
metabolism of the fowl and dietary, environmental and physiological
factors which can cause hepatic steatosis.

INTRODUCTION
Hepatic steatosis is a feature of several infectious and non-infectious diseases of the
fowl and when other abnormalities are not conspicuous the diagnosis is sometimes
uncertain. Apart from fatty liver conditions caused by poisons such as phosphorus or
aflatoxin the most clearly defined diseases in the latter group are known as fatty liver
and kidney syndrome (FLKS) and fatty liver-haemorrhagic syndrome (FLHS). These
affect young chicks and laying hens respectively and appear to be metabolic disorders
with complex aetiologies involving dietary defects. Although they have certain simi-
larities, differences in their biochemistry and pathogenesis are becoming apparent and
at present there is no evidence that they are related aetiologically.
These syndromes are described below and current knowledge of their aetiology and
pathogenesis is reviewed. To form a background for this discussion, it is preceded by
a summary of the relevant aspects of lipid metabolism in the fowl and the mechanisms
by which hepatic steatosis is produced when these metabolic systems are disturbed.

LIPID METABOLISM
Dietary lipids are absorbed mainly from the small intestine. After partial hydrolysis
by lipases in the lumen they form micelles with bile salts and pass into the mucosal
cells where resynthesis occurs. Thereafter the mechanism differs from that in mam-
mals in that the major portion enters the systemic circulation directly as low density
lipoproteins or "portomicrons" (Noyan et al, 1964; Bensadoun and Rothfeld, 1972)
rather than via the lymphatic system as chylomicrons.
However, the diets which are commonly used for fowls contain only a small percentage

Received 9 October 1975

Accepted 20 October 1975
2 E.J. Butler
of fat and the lipids present in the fowl are derived mainly from carbohydrates
(Fig. 1). Besides providing glycerol and the precursors of saturated fatty acids (in the
form of pyruvate), the catabolism of glucose (glycolysis) is also involved in the gen-
eration of NADPH2 (Goodridge, 1968a and b) which is required as a hydrogen donor
by the fatty acid synthetase enzyme present in the cytoplasm (Yun and Hsu, 1972)
and the chain elongation systems located in the microsomes and mitochondria
(Donaldson et al, 1971). Consequently the amount of fat synthesised depends to a
large extent on the activity of the glycolytic system and in turn on the carbohydrate
content of the diet.
Acetyl-Co A carboxylase which catalyses the formation of malonyl-Co A (see Fig. 1)
is believed to be the most important rate-limiting enzyme in cytoplasmic saturated
fatty acid synthesis. Its activity is dependent upon the availability of biotin which is
present as a prosthetic group and is more finely controlled by tricarboxylic acids such
as citrate which behave as activators (Lane et al, 1970) and by long chain acyl-Co A
derivatives, produced partly from dietary lipids, which inhibit the enzyme (Goodridge,
1972 and 1973). Thus at this point in the pathway fatty acid synthesis is regulated by
the intake and metabolism of both carbohydrates and lipids through feed-forward
and feed-back mechanisms respectively. These acyl-Co A derivatives appear to have
the same action on the citrate transfer system. In the longer term lipid synthesis is
coarsely controlled by dietary factors and hormones, such as those secreted by the
thyroid glands and ovaries, which influence the rate at which the lipogenic enzymes
are produced.
The 'non-essential' unsaturated fatty acids such as oleic and palmitoleic acids are
formed from the corresponding saturated acids by the action of desaturation enzyme
systems (Johnson et al., 1969). Glycerides, phospholipids and cholesterol esters are
produced from the Co A derivatives of fatty acids.
When considering the susceptibility of the fowl (and other avian species) to hepatic
steatosis it is important to note that practically all fatty acid synthesis is carried out
in the liver (Goodridge, 1968c; O'Hea and Leveille, 1969; Leveille et al, 1975) and
very little in adipose tissue, whereas in mammals the latter makes a major contribu-
tion. The metabolic activity of the liver is therefore extremely high in the fowl,
especially during egg production when lipogenesis is stimulated by the ovarian hor-
mones. Over half the lipid content of the liver is required for the production of each
egg and the amount synthesised per year is almost equal to the body weight
(Nesheim and Ivy, 1970).
Although adipose tissue has little capacity for fatty acid synthesis in the fowl it does
have a reasonable capacity for incorporating the acids into glycerides and for genera-
ting the glycerol portion. Furthermore, it forms a major storage depot. Lipids are
transported to it from the liver as lipoproteins and are released from the protein and
hydrolysed by an enzyme present in the capillary walls of the adipose tissue (clearing
factor lipase). They are then resynthesised in the adipocytes and stored until they are
hydrolysed and released in response to stress or a reduction in nutritional status.
Mobilisation is very rapid and is brought about by activation of a lipase system by
cyclic 3', 5' - AMP, the formation of which is accelerated by glucagon and ACTH.
At the same time cyclic AMP inhibits lipoprotein lipase thereby controlling the trans-
location of lipids at two vital points. Fatty acids provide an important source of
energy in such an emergency and are transported by plasma albumin to the various
tissues where they undergo (3-oxidation in the mitochondria (Pugh and Sidbury,
1971).
 Fatty liver disease in the fowl 3

Glucose Fatty acids

Fig. 1 Synthesis of saturated fatty acids from carbohydrate. The

lipogenic enzymes are indicated thus:-
1. citrate translocation system, 2. ATP-citrate lyase,
3. acetyl-CoA carboxylase, 4. fatty acid synthetase,
5. 'malic' enzyme.

These and other aspects of the lipid metabolism of the fowl have been reviewed in
more detail elsewhere (Annison, 1971;Pearce, 1974; Butler, 1975).

MECHANISMS OF HEPATIC STEATOSIS

From the above discussion it will be evident that the lipids present in the liver are
derived from 3 main sources, viz. in situ synthesis from dietary carbohydrate, adipose
tissue depots and dietary fats, and that a variety of dietary defects, physiological dis-
turbances and toxic substances can in principle cause the accumulation of fat in the
liver. These include dietary deficiencies of specific nutrients which have in conse-
quence become known as lipotropic factors. The most important mechanisms by
which a fatty liver can be produced involve enhanced lipogenesis, reduced transport
of lipids from the liver, reduced deposition in adipose tissue and decreased oxidation
(see Fig. 2).
Since fatty acid synthesis is coupled to glycolysis a high dietary intake of carbohy-
drate may be expected to cause a marked increase in the fat content of the liver and
this has been demonstrated experimentally on several occasions by feeding a high
energy diet ad libitum or by force-feeding (Barton, 1967; Ivy and Nesheim, 1973;
Wolford and Polin, 1973 and 1974).
4 EJ. Butler

High flux
Low flux

Acetyl-CoA

Fatty Acids
ifol / 1
l [EsTers

ADIPOSE TISSUE
LIVER

Fig. 2. Mechanisms of hepatic steatosis in the fowl

The rate of hepatic lipogenesis is also influenced by the intake of fat but in the oppo-
site direction, there being a depression of fatty acid synthesis when fat is added to the
diet (Weiss etal, 1967; Pearce, 1968 and 1971; Balnave and Pearce, 1969; Leveille et
al, 1975). This has been related to a reduction in the specific activities of two of the
lipogenic enzymes, the citrate cleavage enzyme and the 'malic' enzyme, and may also
be due to an increase in the levels of long-chain acyl-Co A derivatives which are be-
lieved to control the pathway by regulating the activity of acetyl-Co A carboxylase
and the citrate translocation system (Fig. 1). A reduction in the levels of these long-
chain acyl-Co A derivatives may be at least partly responsible for the increase in
hepatic lipogenesis which occurs when the diet is deficient in the essential fatty acids,
linoleic and arachidonic (Edwards, 1967; Hopkins and Nesheim, 1967).
The removal of lipids from the liver in the form of lipoproteins depends on the avail-
ability of the protein moiety and also the phospholipid components which are essen-
tial for the complete assembly of the lipoproteins. Thus a build-up of lipid occurs in
the liver if the protein content of the diet does not supply adequate amounts of the
amino acids required for the synthesis of the apolipoproteins (Marion and Edwards,
1962; Flores et al, 1970) or the synthesis is inhibited by an essential fatty acid de-
ficiency (Fukazawa and Privett, 1972) or a toxic substance such as phosphorus.
Aflatoxin may inhibit the transport of lipids in this way (Carnaghan etal, 1966;
Tung etal, 1972). Hepatic steatosis also occurs if the production of phospholipids
is inadequate and this may be caused by a deficiency of choline or inositol, for exam-
ple, or by a lack of nutrients such as methionine, folic acid or vitamin B 12 which are
involved in the synthesis of choline.
When the lipoproteins reach the adipose tissue the transfer of lipids to the adipocytes
is regulated by the activity of lipoprotein lipase. If this enzyme is inhibited the ani-
mal becomes hyperlipaemic and eventually may develop a fatty liver. Stress produces.
a situation in which this might occur since through the action of ACTH and glucagon
it probably accelerates the production of cyclic AMP which not only inhibits lipopro-
tein lipase but also activates the lipase system in the adipocytes that is responsible for
 Fatty liver disease in the fowl 5

hydrolysing lipids prior to their release. Further research is needed to determine the
significance of these events in relation to hepatic steatosis.
Another metabolic disturbance which can cause the accumulation of fat in the liver
is a reduction in the rate of lipid catabolism. In addition to the )3-oxidation system
this process involves the citric acid cycle and the respiratory chain and can therefore
be inhibited at several points, e.g. by dietary deficiencies of vitamins and trace ele-
ments which are required as co-factors in enzyme systems. The production of fatty
livers by deficiencies of riboflavin (Scott and Krook, 1972) and iron (Amine and
Hegsted, 1971) may be explained in this way.

FATTY LIVER AND KIDNEY SYNDROME

Occurrence
The syndrome, which has also been known as "fat nephrosis" or "pink disease", was
first recognised in Denmark by Marthedal and Vellinge (1958) and has since occurred
in several other countries, including Britain (Hemsley, 1965; Blair et aL, 1969; Hus-
bands and Laursen-Jones, 1969), Australia (Hemsley etal, 1970), Canada (Riddell et
aL, 1971) and India (SahetaL, 1974).
It affects both broiler and layer-type chicks usually when they are 10 to 30 days old,
but outbreaks have occurred in much younger and much older flocks. Chicks from
young breeding stock appear to be particularly susceptible (Hemsley and Marshall,
1973). Genetic factors may also influence susceptibility. Stress, such as may be
caused by high or low temperatures or a lighting failure, seems to be a precipitating
factor and under experimental conditions has been found to increase the mortality
(Whitehead and Blair, 1974; Whitehead et aL, 1975). Withdrawal of food also in-
creases the mortality (Hemsley, 1973a; Whitehead et aL, 1975).
In the field outbreaks have been frequently associated with wheat-based diets con-
taining low levels of protein and fat and the disease has been reproduced experiment-
ally with diets of this kind (Payne etal., 1974; Whitehead and Blair, 1974; Whitehead
et aL, 1974a). However, similar diets containing a different cereal have also been ef-
fective indicating that the energy to protein ratio and the fat content are more im-
portant than the type of cereal (Hemsley et aL, 1973; Blair etaL, 1975).
Clinical features
Well grown chicks become lethargic and aphagic, sometimes show signs of paralysis
and lie on their breasts with their necks extended. Death usually occurs within a few
hours. The overall mortality is generally less than 5% but may exceed 20% in indivi-
dual flocks and extend over several weeks.
Pathology
The most conspicuous macroscopic abnormality is the pale, blotchy and swollen ap-
pearance of the liver and kidneys (Marthedal and Vellinge, 1958; Hemsley, 1965;
Laursen-Jones, 1971). Small haemorrhages are occasionally present on the periphery
of the liver and kidneys and the adipose tissue often has a pinkish tinge due to con-
gestion of the small blood vessels. The heart is sometimes pale and flabby and there
may be excess pericardial fluid. A blackish-brown fluid of unknown significance is
frequently present in the gizzard and the anterior small intestine. The body weight
and the relative weight of the thymus are reduced (Wight and Siller, 1975).
Fatty infiltration of the tissues is widespread occurring not only in the liver, kidneys
and cardiac muscle (Marthedal and Vellinge, 1958; Hemsley, 1965) but also in certain
6 E.J. Butler
skeletal muscles, some regions of the alimentary tract and the central nervous system
(Wight and Siller, 1975; Wight, 1975). Hepatocytes (but not Kupffer cells) show cy-
toplasmic vacuolation due to the accumulation of large amounts of lipid and this is
particularly marked in cells which are in close proximity to the afferent blood supply.
The reticulin pattern is normal. Massive deposition of lipid also occurs in the epithe-
lial cells of the proximal convoluted tubules which are swollen to such an extent that
other renal structures are compressed. Degenerative changes have been observed in
the liver and kidney (Hemsley, 1965;Riddellerai, 1971;Marthedal etal, 1974; Sah
et al, 1974) but do not appear to be a constant feature (Wight and Siller, 1975).
The presence of a lesion in the adrenal glands has been suspected (Payne etal, 1974)
and Wight and Siller (1975) reported a lack of distinction between the cortical and
medullary cells and loss of medullary cell basophilia. They attributed the latter to
severe catecholamine depletion caused by stress. Apart from fatty infiltration no his-
tological lesions have been identified in other organs.
Biochemistry
Affected chicks are hyperlipaemic showing increases in the free fatty acid and tri-
glyceride levels in the plasma and in the lipoproteins with a high triglyceride content
(Evans etal, 1975). There is a 2- to 5-fold increase in the lipid content of the liver
and kidneys which is due almost entirely to an increase in the amount of triglyceride
(Johnson et al, 1972; Whitehead, 1975). This has an abnormal composition in that
the proportion of mono-unsaturated fatty acids (mainly palmitoleic) is increased at
the expense of the saturated acids (mainly stearic).
Death appears to be due to hypoglycaemia caused by a failure of hepatic gluconeo-
genesis and the virtual absence of glycogen (Bannister et al, 1975a) rather than by a
defect in carbohydrate absorption (Bannister etal, 1975b).
Aetiology and pathogenesis
The fact that the incidence of the syndrome can be reduced by increasing the amount
of fat and protein in the diet (Whitehead et al, 1975) has led to the belief that it is
caused by a nutritional defect or imbalance and this theory has been reinforced by
the recent discovery that it can be prevented completely by the addition of biotin to
the diet of the chicks or their parents (Hemsley et al, 1974; Payne et al, 1974; Blair
and Whitehead, 1974). The prophylactic effect of molasses or the residue from their
fermentation observed previously (Hemsley, 1973b and c) can now be attributed to
their biotin content. Moreover, some of the biochemical abnormalities present can
be related to a deficiency of this vitamin. For instance, the impairment of hepatic
gluconeogenesis is attributable to a reduction in the activity of pyruvate carboxylase
which contains biotin and is one of the rate-limiting enzymes in this pathway. Fur-
thermore, the rate of gluconeogenesis is increased in vivo and in vitro by the addition
of biotin (Wight etal, 1975). Hepatic lipogenesis is also reduced (Evans etal, 1975)
as in the biotin deficient chick (Whitehead etal, 1974) and this may be explained in
terms of a decrease in the activity of acetyl-Co A carboxylase which, as was noted
above, also contains biotin.
However, according to the available information on the biotin requirements of the
chick the diets used to reproduce the syndrome appear to have contained adequate
amounts of the vitamin. Attempts have therefore been made to explain how a defic-
iency could be produced in the affected chick and it has been suggested that steam
pelleting of the diet might cause significant inactivation of biotin (Blair etal, 1975),
that its synthesis in the intestinal tract may be impaired by certain dietary constituents
 Fatty liver disease in the fowl •

(Payne etal, 1974) and that its utilisation by the parent hen may be inhibited by the
ingestion of avidin when she indulges in egg eating (Payne etal, 1974). The exact
role of biotin in the aetiology of the disease obviously requires further investigation.
A particularly puzzling aspect of the problem is the absence of the main features of
the classical biotin deficiency syndrome viz. dermatitis, leg deformities and poor
feather development. Furthermore, a simple dietary deficiency of biotin does not
produce hypoglycaemia or hepatic steatosis (Whitehead etal, 1974b). The possibility
that another dietary factor such as a mycotoxin may also be involved has not yet
been entirely eliminated (Johnson etal, 1972).
The hyperlipaemia and the accumulation of lipid in the tissues in FLKS occur despite
a reduction in hepatic lipogenesis and appear to result from decreased transfer of lipid
to the adipose tissue caused by inhibition of lipoprotein lipase (Evans etal, 1975).
No reduction in the rate of lipid oxidation has been detected. This disturbance of
lipid metabolism probably has less significance in the pathogenesis of the syndrome
than the impairment of hepatic gluconeogenesis and may be a secondary feature re-
sulting partly from aphagia.

FATTY LIVER-HAEM0RRHAG1C SYNDROME

Occurrence
This disease was first identified in Texas in 1954 by Couch (1956) who described it
as fatty liver syndrome. Since then it has been recognised in other parts of the U.S.A.
(Ringer and Sheppard, 1963;Nesheimera£, 1969;Wolford etal, 1971; Harms etal,
1972) and in several other countries, including Britain (Anon, 1965), Germany
Greuel and Hartfiel, 1968); Canada (Bragg et al, 1973), France (Brugere-Picoux and
Brugere, 1974) and Australia (Neill etal, 1975), and sometimes has been referred to
as "fat dystrophy", "fatty degeneration" or "liver haemorrhage syndrome". Wolford
and Polin (1972a) proposed that the term fatty liver-haemorrhagic syndrome (FLHS)
be used since it provides a more complete description of the disease.
Outbreaks occur sporadically in laying flocks especially in the heavier breeds when
they are caged or penned and during hot weather. Although there has been no con-
stant association with a particular type of diet, experimental work has shown that
the incidence of liver haemorrhage tends to increase with the amount of rapeseed
meal in the diet (Olomu et al, 1975) and the amount of fat deposited in the liver is
influenced by the cereal used as the basis of the diet (Jensen, 1973; A.W. Pearson,
A.V. Arkhipov and AP. Laursen-Jones, unpublished results).
Clinical features
Egg production may suddenly fall, some of the hens may be obviously overweight
and may have pale combs and wattles covered with dandruff and some may appear to
be unduly nervous, but often there is little indication of the presence of a disease
until deaths occur. The overall mortality is usually less than 5%.
Pathology
Death is invariably caused by massive haemorrhage from the liver which ruptures the
capsule and flows into the abdominal cavity. There are usually signs of the previous
occurrence of smaller haemorrhages underneath the capsule particularly on the mar-
gins of the lobes. The liver is putty coloured and grossly enlarged owing to the
presence of excessive amounts of fat and is very friable. The kidneys are also pale and
swollen. Large amounts of yellow and almost liquid fat are present in the abdominal
cavity and around the viscera. Colour photographs of typical cases have been
8 E.J. Butlei

published by Wolford et al, (1971) and by Wolford and Polin (1972b).

On autopsy many other hens in the flock show similar abnormalities with evidence
of small multiple haemorrhages under the liver capsule. The true incidence of the dis-
ease is therefore very much higher than is indicated by the mortality. There are no
other macroscopic abnormalities and internal laying is not a feature. The diagnosis of
the disease has been confused in the past by the fact that laying hens normally have
much more fat in the liver and adipose tissue than non-layers owing to the stimulation
of hepatic lipogenesis by the ovarian hormones. It is therefore probable that many
outbreaks have not been recognised.
Microscopic examination of the liver shows that the normal architecture is disrupted
by diffuse capillary haemorrhages, organised blood clots, the breakdown of vascular
integrity and areas of necrosis and fibrosis. Some hepatocytes have obviously ruptur-
ed and the remainder are grossly distended with fat which accumulates as globules in
cytoplasmic vacuoles and disorganises the internal structure of the cell. The nucleus
is displaced from its central position and may show signs of degeneration (Rothen-
bacher and Schwartz, 1972) and there are indications that structural changes may
also be present in the mitochondria (Wills and Savage, 1975). Lysis of the reticulin
bands surrounding the cells has also been reported (Hall, 1974;Neill et al, 1975) and
it has been suggested that this produces structural weakness in the liver and is the de-
finitive lesion of the syndrome (Hall, 1974).
A systematic histological examination of other tissues does not appear to have been
carried out and the extent of extra-hepatic fatty infiltration is unknown.
Biochemistry
Analysis of the livers of affected hens gives unusually high figures for the fat content.
These generally exceed 40% dry weight and are sometimes above 70% and largely re-
sult from increases in the amount of triglycerides. They are not diagnostic, however,
since similar levels can occur in hens which show no signs of liver haemorrhage
(Nesheim and Ivy, 1970; Wolford and Polin, 1972a; Wolford and Murphy, 1972).
The composition of the fatty acids present in the lipids is also changed; the propor-
tion of oleic acid being increased consistently (Greuel and Hartfiel, 1968; Ivy and
Nesheim, 1973; Thayer era/., 1973). No unusual lipids have been detected so far.
The effects of the steatosis and the associated cellular changes on liver metabolism
are not yet known. Bromsulphthalein clearance tests have indicated impaired excre-
tory function (Hocke, 1972).
The levels of lipids in the blood plasma (triglycerides and free fatty acids) tend to re-
flect those in the liver but the correlation is too low to be useful for diagnostic pur-
poses (A.W. Pearson, unpublished results). No changes have been detected in the
concentrations of the major plasma proteins (Duke et al, 1968;Neiss etal, 1974),
the glucose level (unlike FLKS) or the activities of glutamate-oxalactate transamin-
ase, /3-glucuronidase and lactate dehydrogenase (Kirchner and Hartfiel, 1974).
Aetiology and pathogenesis
The composition of the liver lipids, the lipid levels in the plasma and the presence of
excess fat in the adipose tissue are consistent with the theory that the hepatic steato-
sis is due largely to increased lipogenesis and it is now widely believed that this is
caused by an excessive intake of carbohydrate resulting from a dietary-environmental
interaction. According to this hypothesis the energy requirement of the hen, which
has already been lowered by the restriction of exercise imposed by the cage or pen,
is reduced further by a high environmental temperature which discourages movement
 Fatty liver disease in the fowl 9

and reduces heat loss. Under these circumstances certain hens are unable to reduce
their food consumption sufficiently to avoid a positive energy balance (Nesheim et
al, 1969) possibly because the diet does not contain enough fibre to satisfy the appe-
tite. Support for this view is provided by experimental work which has demonstrated
the effects of confinement in cages, exercise and environmental temperature on the
lipid content of the liver (Hartfiel e/ai, 1970a; Hartfielerai, 1970b; Wolford, 1971;
Schexnailder and Griffith, 1973). The specific metabolic effects of heat stress in this
situation have not been investigated. In other circumstances release from restricted
feeding might produce the same result by inducing excessive food consumption
(Polin and Wolford, 1973). Obviously if these views are correct the economic cost of
the syndrome must be considered in relation to the waste of cereal as well as in terms
of loss of production and mortality. Until the aetiology of FLHS is better understood
treatment should be aimed at reducing the cereal intake.
However, other aetiological factors have been suspected and some of these have not
been entirely eliminated. Considerable attention has been paid to the possibility that a
dietary deficiency of a specific nutrient might be involved. Couch (1968) recommend-
ed treatment with a dietary supplement of lipotropic agents containing choline, ino-
sitol and vitamins E and Bi 2 . Beneficial effects have been reported (Bull, 1968;
Parker and Deacon, 1968; Reed etal, 1968) but virtually all the trials appear to have
been uncontrolled and are therefore difficult to assess. Many experiments have been
carried out with laying hens to determine whether the addition of these nutrients
either singly or in mixtures to diets, which were presumably adequate, reduces the
fat content of the liver but the results have been inconsistent and no general conclu-
sion can be drawn from them regarding the aetiology of FLHS or its treatment
(Barton, 1967;Griffith etal, 1969;Nesheim etal, 1969; Bossard and Combs, 1970;
Leveille and Bray, 1970;Ragland etal, 1970;Hartfiel etal, 1971; Nesheim etal,
1971;Pearce, 1972; Wolford and Murphy, 1972; Griffith and Schexnailder, 1972;
Schexnailder and Griffith, 1973; Jensen etal, 1974; Wolford and Polin, 1975). Other
vitamins, including biotin, and selenium have also failed to give consistent responses
(Wolford and Murphy, 1972; Schexnailder and Griffith, 1973; Jensen et al, 1974).
Other dietary factors that might have a secondary or contributory role include pro-
tein intake, constituents of rapeseed meal and certain cereals such as maize, and
certain mycotoxins. Aflatoxin produces both hepatic steatosis and haemorrhage and
had been investigated as a possible factor (Hamilton and Garlich, 1971). However,
since it produces other distinctive lesions in the liver (Carnaghan et al, 1966; Miiller
et al, 1973) its involvement is very unlikely.
While it is probable that the hepatic steatosis is due to increased lipogenesis (thereby
differing from that in FLKS) it has not yet been established that this is the sole
mechanism or that this pathway is the site of the primary biochemical lesion. The
catabolism and transport of lipids and their deposition in adipose tissue should also
be examined further. The relationship between the steatosis, the reticulolysis and
the haemorrhage from the liver is another aspect that requires further investigation.
These abnormalities may be related causally and it is possible that the reticulin bands
and the walls of the blood vessels are weakened by the infiltration of fat. Support,
but not unequivocal evidence for this theory is provided by the results of recent ex-
periments which showed that both the fat content of the liver and the incidence of
haemorrhage can be increased by force-feeding laying hens (Wolford and Polin, 1974)
or by injecting immature fowls repeatedly with oestradiol (Wolford and Polin, 1973;
A.W. Pearson, unpublished results). On the other hand hepatic steatosis may simply
10 E J.Butler

predispose the hen to the action of some other factor which causes the reticulolysis
and/or the haemorrhage.

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 Fatty liver disease in the fowl 11

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12 EJ. Butler

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14 E.J. Butler

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RESUME
Revue sur la ste'atose hépatique de la poule
L'auteur décrit les troubles métaboliques généralement dénommes "Stéatose hépato-
rénale" et "Syndrome stéatose hépatique". Il discute de leur pathogénie et de leur
étiologie d'après les connaissances actuelles sur le métabolisme des lipides chez la
poule, et de l'influence des facteurs alimentaires, zootechniques et physiologiques sur
la maladie.

ZUSAMMENFASSUNG
Krankheiten mit Leberverfettung beim Geflügel.
Übersichtsreferat.
Die Stoffwechselstörungen, die als Fettleber-Nieren-syndrom und Haemorrhagisches
Fettlebersyndrom bekannt sind werden beschreiben. Ihre Pathogenese und Aetiologie
wird in Bezug auf die derzeitigen Kenntnisse über den Fettstoffwechsel des Geflügels
und über Lebersteatose auslösende Ernährungs-, Umwelt- und physiologische Faktoren
diskutiert.