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

VIII. Ketogenesis and Ketosis
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term because fetal glucose demands increase with increasing
body size. The ovine placenta is capable of extracting
glucose from maternal plasma at concentrations below
1 mmol/l and readily does so. It might seem biologically
useless for the fetuses to cause a fatal hypoglycemia in
the ewe, which will also lead to their own demise, but the
fetuses are highly dependent on glucose as a caloric and
synthetic source and would expire without it anyway.
Fetal lambs normally maintain a very low plasma glucose
concentration of approximately 0.6 mmol/l compared
to 2.7 mmol/l in a ewe ( Warnes et al ., 1977 ). Thus, the
transplacental glucose gradient greatly favors movement
from dam to fetus. Curiously, the most concentrated carbohydrate
in fetal sheep plasma is fructose (5.1 mmol/l),
which is synthesized from glucose in the placenta by
reducing glucose to sorbitol followed by oxidation to fructose
( Hers, 1960 ; Warnes et al ., 1977 ). Despite the abundance
of fructose in the plasma of the fetal sheep, glucose
constitutes its primary energy supply ( Lindsay and Pethick,
1983 ; Warnes et al ., 1977 ), and the fetuses normally consumed
60% to 70% of maternal glucose production ( Prior
and Christenson, 1978 ; Setchell et al ., 1972 ).
The ovine placenta appears to have a low permeability
for acetoacetate. When acetoacetate loads have been
infused into pregnant sheep, the concentrations in fetal
blood have remained low. Further, in vitro experiments
with perfused sheep placenta have also demonstrated a
low permeability for acetoacetate ( Alexander et al ., 1966,
1969 ). Thus, it appears that maternal acetoacetate, and perhaps
3-hydroxybutyrate, cannot be a major energy source
for the ovine fetus.
The disease is characterized by depression and weakness
in the ewes, which are associated with hypoglycemia,
ketonemia, and ketonuria (Henze, 1998; Reid, 1968 ). The
ketonemia is severe enough to cause acidosis, which can
be severe ( Holm, 1958 ; Reid, 1968 ). There is also considerable
fatty deposition in the liver to the extent that it may
interfere with liver function ( Cornelius et al ., 1958 ; Snook,
1939 ). Eventually, the ewes are unable to rise, become
comatose, and die if untreated.
Mild cases respond to intravenous glucose, glucocorticoids,
glucose precursors such propylene glycol or glycerol
coupled with removal of stress, and improved nutrition
( Henze et al ., 1998 ; McClymont and Setchell, 1955a,
1955b ; Thompson, 1956 ). Severe cases, in which the ewes
are unable to rise, usually respond only to delivery of the
lambs, and even then, a high mortality will occur ( Holm,
1958 ; Reid, 1968 ).
3 . Syndromes in Other Species
Ketosis associated with lactation can occur in dairy goats
( Morand-Fehr et al ., 1984 ). The syndrome has also been
reported in beef cows with caloric deprivation and nursing
two calves ( Khan et al ., 1986 ). Pregnancy toxemia
has been reported in goats carrying multiple fetuses ( East,
1983 ; Morand-Fehr et al ., 1984 ; Rindsig, 1980 ; Thedford,
1983 ). The syndrome can be produced with calorie deprivation,
particularly if coupled with stress, and almost always
occurs in does carrying more that one fetus. Obesity also
may be a predisposing factor in does ( Morand-Fehr et al .,
1984 ; Thedford, 1983 ). Generally, the syndrome in does
appears entirely similar to that in ewes.
Pregnancy toxemia has been reported in beef cows in
the last 2 months of gestation ( Caple et al ., 1977 ; Kingrey
et al ., 1957 ; Sampson et al ., 1945 ; Tyler et al ., 1994 ). The
disease occurs predominantly in cows that are carrying
twins. The cows may be in good or even obese body condition,
but sudden food deprivation or decrease in quality
or imposition of stress such as water deprivation may precipitate
the syndrome. The disease resembles pregnancy
toxemia in sheep in most respects. Pregnancy toxemia has
been reported in pregnant bitches ( Irvine, 1964 ; Jackson
et al ., 1980 ) and appears similar to the disease in sheep.
Hypoglycemia is severe in canine cases, and the animals
respond readily to intravenous glucose. If the animals will
eat a carbohydrate-containing diet, a relapse is unlikely;
otherwise, removal of the fetuses is required for a cure.
There is a report of diabetic ketosis developing in pregnant
dogs, which may resolve after delivery; however, these
dogs are hyperglycemic and are treated with fluids and
insulin ( Norman et al ., 2006 ). Pregnancy toxemia occurs
in pregnant guinea pigs and, like in pregnant ewes, the syndrome
can be precipitated by inadequate calories and stress
( Bergman and Sellers, 1960 ; Wagner, 1976 ). The syndrome
in guinea pigs is similar to that in sheep. There is marked
ketonemia and acidosis, and the animals become weak and
depressed with eventual coma ( Wagner, 1976 ).
I. Postexercise Ketosis
Postexercise ketosis, which was first documented in 1909
( Forssner, 1909 ), has been investigated most extensively
in humans and rats. Neither trained nor untrained humans
or rats show much increase in ketones during exercise, but
only untrained individuals exhibit a significant ketonemia
and ketonuria after exercise ( Johnson et al ., 1969 ; Koeslag,
1982 ; Winder et al ., 1975 ). The experiments of Winder et al .
(1975) demonstrated a greater enzymatic capacity of muscles
of trained rats to catabolize ketones. It also appears that
trained athletes have a greater capacity to oxidize LCFA in
muscle than nonathletes ( Johnson et al ., 1969 ). A high-carbohydrate
diet in conjunction with training also decreases
the magnitude of postexercise ketosis ( Koeslag et al ., 1980 ).
From the foregoing, it appears that a number of factors
are involved in postexercise ketosis. During exercise,
all forms of fuel, including LCFA, ketones, and glucose,
are oxidized. Postexercise, there is a diminution of LCFA
release from adipose tissue; however, plasma LCFA concentrations
decrease little at first because of an even greater