Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

VIII. Ketogenesis and Ketosis
105
H. Ketosis Associated with Pregnancy
and Lactation
These ketoses are most commonly observed in ruminants
although they have been documented in dogs and humans.
Before specific syndromes are discussed, a general picture
of ketogenesis in pregnancy and lactation will be presented.
Fetal demands for glucose are high, and the placenta
can transport glucose from maternal to fetal plasma
( Setchell et al ., 1972 ; Warnes et al ., 1977 ). When an
imbalance occurs between the maternal ability to synthesize
or absorb glucose and fetal consumption, hypoglycemia
results. Under these circumstances, hypoglycemia will
lead to lipolysis in adipose tissue and release of LCFA as
discussed earlier. The LCFA will be taken up by the liver
and converted to ketones with resulting ketosis.
Ketosis in lactation is somewhat more complex than
ketosis occurring during pregnancy. The volume of milk
produced is almost totally dependent on the rate of lactose
synthesis by the mammary gland because milk volume formation
is an osmotic phenomenon, and lactose is the predominant
molecular species in milk ( Peaker, 1977 ). There
is virtually only one precursor of lactose, and that precursor
is plasma glucose ( Bickerstaffe et al ., 1974 ; Kleiber et
al ., 1955 ). Therefore, a female that is in heavy lactation
will have a heavy drain on plasma glucose. There are two
sources of plasma glucose: absorption from the gut and
gluconeogenesis.
In ruminants, little glucose is absorbed from the gut, so
the overwhelming bulk of it is synthesized ( Lindsay, 1959 ;
Otchere et al ., 1974 ). Most (approximately 90%) of this
synthesis occurs in the liver with the remainder occurring
in the kidney ( Bergman, 1982 ). The chief substrates are
propionate and amino acids, with the former being most
important in animals on a high-grain diet. Other precursors
are branched chain VFA and lactate absorbed from the
rumen and glycerol released during lipolysis ( Bergman,
1975 ). If there is a mismatch between mammary drain of
glucose for lactose synthesis and gluconeogenesis in the
liver, hypoglycemia will result. Under these circumstances,
hypoglycemia will lead to ketosis as explained in the discussion
on fasting ketosis.
1 . Bovine Ketosis
Bovine ketosis is actually at least three different syndromes
that occur in cows during lactation ( Kronfeld, 1980 ;
Kronfeld et al ., 1983 ). The syndromes are characterized by
anorexia, depression (usually), ketonemia, ketolactia, ketonuria,
hypoglycemia, and decreased milk production. The
three syndromes are underfeeding ketosis, alimentary ketosis,
and spontaneous ketosis.
Underfeeding ketosis occurs when a dairy cow receives
insufficient calories to meet lactational demands plus body
maintenance. This version of ketosis can be conveniently
divided into nutritional underfeeding ketosis and secondary
(or complicated) ketosis. The former occurs when the cow
has a normal appetite but is given an insufficient quantity
of feed or a diet with low metabolic energy density. The
latter occurs when a cow has some other disease, such as
hypocalcemia, mastitis, and metritis, which suppresses
appetite and causes the cow to consume insufficient nutrients.
In most respects, underfeeding ketosis resembles
starvation ketosis explained earlier, except that there is the
additional caloric and glycemic burden of milk production.
Alimentary ketosis occurs when cattle have been fed
spoiled silage that contains excessive amounts of butyric
acid ( Adler et al ., 1958 ; Brouwer and Kijkstra, 1938).
As discussed previously, the rumen epithelium has a
high capacity to activate butyrate to acetoacetate and
3-hydroxybutyrate. Under conditions where excessive
butyrate is presented to the rumen epithelium,
large amounts of 3-hydroxybutyrate will be produced
and released to the circulation with resulting ketosis.
Alimentary ketosis then is really butyrate toxicosis.
Spontaneous ketosis is probably the most common,
the most researched, the most controversial, and the least
understood form of bovine ketosis. It occurs in high producing
dairy cows that are near the peak of lactation, that
have access to abundant high-quality feed, and that have no
other disease ( Baird, 1982 ; Kronfeld, 1980 ). The disease is
not accompanied by severe acidosis ( Sykes et al ., 1941 ),
and spontaneous recovery is common although there is a
large decrease in milk production ( Baird, 1982 ; Kronfeld,
1980 ). There are several schemes proposed for the molecular
pathogenesis of the syndrome. As these schemes are discussed,
it will become evident that they are not necessarily
mutually exclusive, and more than one of them may be correct
and may be present simultaneously in the same animal.
The most widely accepted theory of bovine ketosis is the
hypoglycemia theory ( Baird, 1982 ). In this theory, hypoglycemia
is the driving force in the syndrome and ultimately
causes the ketonemia. Dairy cows are selected for remaining
in the herd more for milk production that for any other factor.
Thus, dairy cows have been selected for many generations
to have a metabolically aggressive mammary gland. This
selection criterion has dictated that the mammary produce
a maximum amount of milk with secondary regard for the
metabolic consequences for the rest of the animal. It is not
surprising, therefore, that occasionally the mammary gland
might withdraw glucose from the plasma more rapidly than
the liver can resupply it, which leads to hypoglycemia even
in a well-fed animal. The hypoglycemia will lead to ketonemia
by mechanisms discussed earlier and later in this discussion.
The hypoglycemia and ketonemia may cause the cow
to be ill enough that she will decrease her feed intake. At this
point, the syndrome will resemble underfeeding ketosis.
As explained previously, high milk production equates
to a high rate of plasma glucose utilization by the mammary
gland, which equates to a high rate of hepatic