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Stress, Drugs and Immunity
By Linda Aronson, DVM
The immune system is an interactive network of cells and
proteins designed
to protect the body from pathogens in the environment,
parasites, malignant
cells, allergens and toxins. The system has specific and
non-specific moieties
to protect and serve. The latter includes the barriers of
skin and mucous
membranes, non specific Natural Killer (NK) cells that
destroy anything that
isn’t self, phagocytes – cells that engulf and neutralize
anything alien and various
chemical defense mechanisms. Other cells are produced in
response to
a particular invader. In the blood we circulate antibodies (immunoglobulins)
produced by B cells that neutralize specific viruses and
toxins. Together with “complement” proteins they also
destroy and clear out invading bacteria.
The bone marrow makes large macrophages– big
eating machines - and B
cells, while the thymus gland in the neck produces T-cells
(there are three
types, one turns on B-cells, another turns on the third type
of T-cells the
ones that destroy virus and tumor infected cells). Like any
army, the immune
system needs to coordinate and communicate, and it does so
through
hormone like substances called cytokines– including
interleukins (ILs),
interferon (INF) and tumor necrosis factor (TNF).
Psychological stress
causes sleep disturbances, decreased appetite and delays
wound healing.
Restraint, isolation and physical manipulation are very
stressful to animals.
Unfortunately, going to the vets tends to involve many of
these stressful procedures
and in an already sick dog may contribute to a worsening of
his condition.
Vets can help minimize the stress by making sure pets that
require hospitalization
are kept in adequately sized cages, that floors are dry, the
environment
is comfortable and clean and at an optimal temperature,
noise should be
minimized; species kept separately,water and food of good
quality and
appropriate for the animal’s condition provided, and periods
of light and dark
maintained so that the dog’s normal patterns of rest and
sleep aren’t disturbed.
Many vets will provide Dog appeasing pheromone diffusers,
pheromones
mimicking those produced by bitches when they nurse their
puppies,
and which calm and comfort many agitated dogs. Owners who
have trained
their dogs to accept all manner of handling and have them
crate trained while
they are healthy can help minimize the stress their dog
experiences when being
examined or hospitalized. Physical stress – surgery and
trauma – as well as
psychological stress result in suppression of the immune
system.
As we might expect surgical trauma causes a reduction in the
immune response,
however - beyond the physical stress, the psychological
stress and the
pain often present before but also involved in the surgery -
anesthesia itself
causes immunosuppression. These multiple stresses to the
system can lead
to postoperative problems – hypothermia,low blood pressure,
increased pain, sleep difficulties, impaired
respiration,increased cardiac demand, gastrointestinal
problems – ulcers and/or
loss of normal motility - as well as loss of appetite,
weight loss, delayed healing,
infection and growth of malignant tumors.Controlling pain
before, during and
after surgery is of paramount importance. It has been shown
that the more
pain an animal experiences, the more likely that any tumor
present will metastasize.
Most effective in blocking endocrine metabolic responses is
the
use of analgesics applied to nerves serving the surgical
site – nerve blocks,
spinal and epidural anesthesia. Local/ regional anesthesia
can abolish surgical
stress. Maintaining the block post surgically can further
reduce immunosuppression
and speed healing. Opioids and non steroidal
anti-inflammatory
drugs (NSAIDs) have little effect in reducing stress at
recommended doses,
although they do reduce inflammation,which infiltrative
anesthetics do not
affect. Some immune cells however,have opioid receptors; and
T and perhaps
B cells can produce opioid immunopeptides – beta-endorphin,
enkephalin
and dynorphin. Local application of opioids is far less
likely to
produce immunosuppression, and can be very helpful in
treating such conditions
as arthritis.Other preoperative strategies that may help
reduce surgical stress are a single
dose of glucocorticoids; in patients with heart disease beta
blockers are
helpful; adequate nutrition, especially feeding
carbohydrates, may stop the
body breaking down muscle and other tissues.Hypothermia is a
threat to surgical patients
on several fronts. Immunosuppression makes the body more
susceptible
to bacterial infections. Blood vessels constrict near the
skin, and reduce
blood flow that is needed for repair of damaged tissues and
further decreases
the activity of local immune defense factors. Neutrophil –
white blood cell
– function is compromised so they are less effective at
eliminating bacteria,
the production of cytokines and reproduction of T cells is
also reduced.
Even a central hypothermia of 1.9oC tripled the incidence of
surgical wound
infections in one study. Lowered blood pressure, as a result
of blood loss and
various anesthetic agents, further exacerbates these
problems.
The longer the animal is anesthetized and surgery lasts, the
greater the risk of infection of the
wound and respiratory infection. One study
showed that insurgeries lasting less than an hour, the
concentration of B and T cells took about 7 days to return
to normal, but
for longer surgeries the return to normal took significantly
longer.
Because of the immunosuppression produced by anesthesia and
surgery,
vaccinations should not be given at the time of surgery, and
elective surgery
should be delayed at least 3 weeks after vaccination. This
must obviously be weighed against further stress when
dealing with wild or feral animals, but in the domestic dog
there is no medical
excuse to vaccinate an animal at the time of surgery. This
practice can not
only diminish the immune response to and efficacy of the
vaccine, but is more
likely to result in anaphylactic (allergic) reaction,
thrombocytopenia
(lowering of platelets and risk of bleeding).
Anaphylactic reactions are often fatal,
and may be delayed up to 48
hours. Modified live vaccines (MLV)are particularly
associated with thrombocytopenia,
which could obviously be dangerous and lead to excessive
post
operative bleeding and other complications.The use of
NSAIDs and some
other drugs could worsen these complications. Dogs with
undiagnosed von
Willebrand’s disease or hemophilia would be at
particular risk. MLVs may
also induce a mild viral infection, fever,anorexia and
lethargy, all of which
would be more serious in the post surgical patient.
Similarly, elective surgery should never be performed on
dogs that are sick. In
the case of emergency surgery all efforts must be made
to reduce both surgical
and psychological stress in the debilitated animal.
While there has
been some disagreement between various studies, there is
evidence that anesthesia
and surgery do make metastasis,particularly to the lung,
of tumors more
likely. Because morphine decreases natural killer
efficacy there may be
increased growth of tumors post surgically if opioids
are used for pain relief.
However, even worse is providing no pain relief as this
really promotes tumor
growth.Surgery, even simple tooth cleaning and other
minimally invasive practices,
is not to be taken lightly. At some time or other most
of our Beardies are going
to have to be anesthetized and I hope that this article
has clarified why we
need to look at the general health of a dog – including
looking at the CBC and
biochemistry profile – before we consider elective
surgery. Because of the
immunosuppression we need to bolster the dog’s natural
immunity, and antibiotics
may be started even before surgery begins. Always make
sure your
vet knows about any medical conditions your dog has,
because this may
affect the choice of appropriate drugs to use for
anesthesia and pain relief.
Make sure your Beardie is given pain relief; he will
heal better and faster.
Never agree to vaccinations being given at the time of
surgery. Most important
of all, before your dog ever needs surgery, make sure he
is comfortable
with different situations and being handled by
strangers. Make sure he is
used to being crated. If you do this you will have done
your best to ensure his
well-being when he is sick, so that he can come through
medical procedures
and surgery with minimal stress and a much healthier
immune system to
speed his recovery.
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A big thank you to Linda Aronson,DVM, for
her contribution to PON Digest
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