Page 1163 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Nonprotein Nitrogen (Urea) and Hyperammonemia Chapter | 79 1095

VetBooks.ir of value in particular circumstances (e.g., the rapid
growth phases of pregnancy and postpartum periods of
high milk production in highly productive animals).

TOXICITY
Depending on dose, all mammalian species are potentially
susceptible to NPN poisoning via the consumption of
ammonia-containing feeds (Hintz et al., 1970). However,
NPN poisoning is most commonly observed in ruminants.
In ruminants, if NPN is consumed at a rate that exceeds
the capacity of the rumen microflora to convert it into
microbial protein, then free NPN (typically free ammonia
or free ammonium, depending on pH) will remain in the
FIGURE 79.1 Acid base fractional composition (α 5 0 5 0% frac- rumen fluid. At normal rumen pH (pH 6.5 7.0), free
tional composition; α 5 1 5 100% fractional composition) as a function
1 ammonia (NH 3 ) will be rapidly protonated to ammonium
of pH for ammonia (NH 3 ) and ammonium ions (NH 4 ) (Fractional 1 2
(NH 4 ) with the coproduction of hydroxyl ions (OH ).
composition (α) for a simple monoprotic acid base relationships can be
calculated using the following equations: This results in an increase in rumen pH (Lower and
Fraser, 2016). When rumen pH rises above approximately
1
H ½ HAŠ
α 0 5 5 ; α 1 5 K a pH 8, the ammonia ammonium equilibrium reaction
H ½ 1 Š 1 K a A ½ 2 Š 1 HAŠ H ½ 1 Š 1 K a
½
2 strongly favors the formation of free ammonia (NH 3 ;
A ½ Š
5 Þ: black line in Fig. 79.1). Since the free ammonia (NH 3 )
½
A ½ 2 Š 1 HAŠ
form is unionized and more lipophilic, these conditions
also favor systemic absorption through the rumen wall.
Once the systemic absorption of ammonia (NH 3 ) exceeds
ranges from 10% to 40% of nitrogen consumed in feed
the animal’s capacity to excrete it or metabolise it, hyper-
depending on species and conditions, water intake and the
ammonemia and toxicity develop. In non-NPN adapted
nature of the feed available also affect the response). Urea
ruminants, these reactions can occur relatively quickly
can also be directly absorbed through the rumen wall and
(e.g., within 30 min to hours in animals that are not
can also be recycled to the digestive tract. Camelids, in
adapted to NPN sources and/or after feed mixing errors).
comparison with ruminants, are much more efficient at
Hyperammonemia inhibits the citric acid cycle (Hatch,
conserving nitrogen under conditions of low protein nutri-
1977), resulting in metabolic lactic acidosis, interference
tional stress. Under these conditions, this species excretes 1 1
with cerebral energy metabolism and failure of Na -/K -
only 1% 2% of systemically available nitrogen, with the
ATPase pumps with resultant hyperkalemia. Factors that
remainder being recycled into the rumen.
potentially predispose ruminants to dietary ammonia poi-
soning include low energy diets, high rumen pH (e.g.,
THE BIOLOGICAL VALUE OF RUMEN rumen impaction), elevated body temperature (increases
MICROFLORA PROTEIN rumen microflora urease activity), and dehydration, stress,
concurrent disease, alterations in rumen microflora, insuf-
When NPN is used as the only source of dietary nitrogen, ficient rumen microflora adaptation time and hepatic
the rumen microflora can produce all the amino acids that insufficiency. A lack of readily available soluble dietary
are essential for growth, wool production, and milk pro- carbohydrates markedly affects the rumen bacteria’s abil-
duction provided other dietary requirements are adequate, ity to utilize the ammonia for protein synthesis.
i.e., effective conversion of dietary NPN to tissue, wool Most NPN poisonings in ruminants occur as a result of
and milk proteins occurs in ruminants (Loosli and inadequate implementation of an adaptation period, improper
McDonald, 1968). Irrespective of the dietary nitrogen mixing of the supplement into the diet (including hot spots of
source, the resultant microbial protein tends to have a bio- NPN concentration), and unlimited/unrestricted access to
logical value of 60% 70% (biological value measures palatable liquid NPN supplements. Adaptation of the rumen
the proportion of absorbed dietary protein from a food microflora to dietary NPN sources takes several days. The
that is subsequently incorporated into the organism’s pro- use of anticaking agents to prevent the formation of areas of
teins, i.e., it is a measure of how readily digested dietary high urea concentration in the ration is an important
protein can be used in protein synthesis in the cells of the preventative strategy in solid preparations. NPN poisoning in
organism). Insoluble rumen bypass dietary protein is still monogastric animals is uncommon.