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| Copyright © 2003 The Diabetes Insipidus Foundation, Inc. | |
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Diabetes Insipidus In Our Best
Friends A
disease that many people have never heard of may be indirectly causing
canine deaths. Not only is the disease dangerous in itself, but the
primary symptoms include a behavior that could be perceived, or
misinterpreted by owners, trainers, and veterinarians as purposefully
destructive, and which figures prominently in the statistics of animals
turned over to dog pounds and to veterinarians for euthanasia. The
behavior we are referring to is the
need for frequent urination. Seldom do owners and veterinarians search
for potential medical problems that might contribute to house soiling
behaviors. And, if they do, seldom are those searches for medical causes
of inappropriate elimination practices complete. At least a quarter of
all dogs euthanized or turned into
shelters are given up because of behavior-related issues. Near the top
of the list of reasons for euthanasia and being turned into shelters is
house soiling.[i]
Therefore, whenever an inappropriate elimination behavior develops, look
first for an underlying medical condition before starting training or
behavior modification exercises. While
diabetes insipidus (DI) is less common than the better-known diabetes
mellitus, it is probably an under-reported disease as it shares symptoms
with other more common diseases, including diabetes mellitus. The
disease can also go unnoticed if the dog has a constant supply of water
and has access to an outdoor run or a doggy door so that his excessive
elimination needs do not require human intervention. Nonetheless, the
disease is dangerous, and severe dehydration can occur very rapidly
(within four to six hours). Leaving a “DI dog” unattended without
water for several hours or overnight may result in severe
hyperosmolality, coma, and death.[ii] Dr.
Marie Monaco, whose female Samoyed struggled with the problem, going in
again and again to the vet until the problem was recognized, says “We
would never have known there was a problem if India had had access to a
yard.” India was fortunate enough to be seen by a vet familiar enough
with the problem to be able to eventually make the proper diagnosis. Dr.
Gail Zausner [iii]
has seen several other patients with this disease since she first
diagnosed Monaco’s Samoyed. “I caution all dog owners to be on the
look out for changes in drinking and urination patterns,” she says.
Water consumption exceeding 100 ml/kg or urine production exceeding 50
ml/kg body weight per day is common to both types of DI. These rates
should be viewed as guidelines as environment, activity levels, etc.,
may cause significant variance.[iv] DI
is characterized by extreme thirst and frequent copious urination. DI
exists in two forms in dogs, central
diabetes insipidus (CDI) and nephrogenic diabetes insipidus (NDI).
CDI
and partial CDI can be either congenital
(existing since birth) or acquired later in life. Dogs of any age, sex,
and breed are at risk for CDI. On the other hand, NDI is a rare genetic
disorder, usually diagnosed in younger animals. Kidney
Function
To
understand DI, in any of its forms, requires a general understanding of
how the kidneys function, and how various hormones regulate that
function. The
kidneys are a pair of
bean-shaped urinary organs that lie below the lumbar region of the
vertebrae on either side of the spinal column. The major
role of the kidneys is to maintain fluid and electrolyte balance
and to rid the body of toxic metabolic waste products. To do this, the
kidneys filter blood and produce urine. Three basic processes are
involved in the formation of urine:
glomerular filtration, tubular reabsorption and tubular secretion.
The smallest functional unit capable of
producing urine is called a nephron.
These tiny filtration units filter the blood under high pressure,
removing urea, salts, and other soluble wastes. The filtered and
purified fluid is then returned to the blood in amounts necessary to
maintain the water balance of the body. The wastes are accumulated and
excreted as urine. To explain these rather complicated processes, let us
follow the course of a molecule of water as it enters the kidney from
the bloodstream. As necessary, please refer to Figure 2. •
The water molecule
carried in the blood enters one of the kidneys from the aorta by way of
either the left or right renal artery. •
The renal arteries
branch out into smaller and smaller arteries and finally to the smallest
arteries called afferent arterioles. It may help to think of the
branching process as a major limb on a tree branching into smaller and
smaller branches. •
The kidney controls
filtration pressure by secreting renin, which in turn leads to the
formation of angiotensin II which causes the arterioles to contract,
thus raising the blood pressure. •
Each afferent arteriole in the cortex
of the kidney branches into a ball-like mass of very tiny, coiled and
intertwined capillaries called a glomerulus. Given the number of
afferent arterioles, there are thousands of glomeruli in the cortex
region of each kidney. •
As blood passes through the glomeruli, the filtration, reabsorption and
secretion processes begin. ••
Filtration--The walls of the glomerulus are selectively permeable
permitting the passage of water, salts, sugar and nitrogenous wastes
such as urea, creatinine and uric acid to filter out of the blood. Each
glomerulus is surrounded by a cup-like structure called the Bowman’s
capsule that collects the filtrate. Large
protein molecules and blood cells are too large to pass through the
glomerular walls, and thus are retained in the blood. ••
Reabsorption—The
Bowman’s capsule collects the resultant blood plasma where it then
passes into the proximal end of the renal tubule (a long, twisted tube).
Tiny capillaries close to the renal tubule then selectively reabsorb the
substances the body needs. Only wastes, some water, some acids and some electrolytes
(charged ions necessary for certain processes in the body) make it past
this system of tiny capillaries. The rest is returned to the
blood via these tiny capillaries. At
this point, our water molecule could passively diffuse back to the
bloodstream in a process called osmosis or it could continue down the
renal tubule. When the filtrate first enters the tubules, cloride ions
are actively pumped out of the plasma
and returned to the bloodstream. This makes the bloodstream have
more dissolved substances in it then the plasma. Conversely, the
concentration of water to dissolved substances within the tubules is
greater than that of the blood stream. It is a fact of nature, that if
allowed to, water will move from a place of higher concentration to one
of lower concentration. This process is called
osmosis. Approximately 80% of the water in the plasma is passively
returned to the body within the tubular system. Recently discovered
water channels called aquaporins facilitate this process. If
our water molecule did not get reabsorbed at this point, it would then
continue through to the distal (far) end of the tubular system where
further reabsorption would take place under hormonal control. If not
absorbed by the end of the renal tubule journey, our water molecule
would go to the renal pelvis and from there to the ureter, the bladder
and eventually to the urethra and urinary meatus (opening) for
excretion. Hormones
control the function of the kidneys in regulating the water content of
the body. The hypothalamus, a small but very important gland located in
the middle of the brain, manufactures the antidiuretic hormone, ADH
(also known as arginine vasopressin) for subsequent storage in the
pituitary gland that is attached to the hypothalmus by a thin stalk. ADH
is released when the blood volume falls, when a large amount of salt
shows up in blood, or when pain or stress are present. ADH release by
the pituitary gland stimulates reabsorption of water into the blood. If
water intake is not enough to make up for the water lost in perspiration
and in breathing, the pituitary gland releases more ADH, thus reducing
the amount of water released in urine. If the blood is too dilute, the
pituitary gland reduces the secretion of ADH, causing a larger flow of
water into urine. This negative-feedback control is stimulated by a
water deficit. Too
little ADH released results in an over-excretion of dilute urine,
dehydration and death. Vasopressin reaches the membrane of the tubular
cells lining the distal and collecting tubules by way of the circulatory
system, whereupon it binds with specific receptor sites. This binding
activates a process called the cyclic AMP second messenger system that
in turn initiates the insertion of the water channels into the cell
membrane. Many hormones do not actually enter their target cells.
Instead, these “first messengers” issue their commands by the
binding of receptors on the surface of the cell membrane and initiate a “PPsst,
pass it on” process. Two
types of Diabetes Insipidus
Both
forms of DI share a lack of, or inability to use the hormone arginine
vasopressin with the subsequent result that water is not retained by the
body. In summary: •
Central
diabetes insipidus (CDI), also known as “vasopressin-sensitive DI,”
is a disorder of water balance where there is a lack of or an inadequate
amount of antidiurectic hormone (ADH). Therefore the dog is unable to
concentrate urine. The
underlying cause may be a congenital defect, trauma or a tumor on the
hypothalamus where ADH is manufactured or damage to the pituitary where
it is subsequently stored for future release. Recent research has shown
that a possible genetic cause of CDI maybe a mutation in the protein
responsible for the proper cleavage of the initial form of the
vasopressin hormone. [v]
Signs
and Tests:
polyuria (excessive urination) and polydipsia (excessive drinking),
electrolyte imbalance, possible dehydration, low ADH levels, urinalysis
shows a low specific gravity. Diagnosis:
1) ruling out other causes, to include Cushing’s disease, diabetes
mellitus, renal failure, liver disease, and pyometra in bitches; 2)
imagery of the pituitary with a positive finding of a tumor; 3) water
deprivation test—if animal is unable to produce more concentrated
urine as water intake is restricted; 4) ADH trial with desmopressin
(the drug used to treat DI)—a positive response to the drug indicates
the dog has DI Treatment:
Intranasal, oral tablet, eyedrop, or subcutaneous injection
administration of desmopressin. Prognosis:
Variable, but not life threatening if treated and adequate fluid intake
is maintained. •
Nephrogenic diabetes insipidus (NDI), also known as
“vasopressin-resistant DI,” is a disorder of water balance where the
pituitary produces adequate ADH, but for some reason, the kidneys do not
respond to it. There are in essence two kinds of NDI: 1) where damage or
mutation has occurred and the activity of the receptor site in the
kidney is disrupted; and 2) where the aquaporins fail for some reason to
fail to adequately support the passive return of water to the blood. In
either case, the kidney fails to respond to adequate levels of ADH. Signs:
Same as for CDI. Diagnosis:
Same as for CDI, except that if urine does not become more concentrated
after ADH testing, this indicates failure of the kidney to use ADH. Treatment:
Oral chlorothiazide(a thiazide diuretic) to help the kidneys concentrate
urine. Thiazides paradoxically reduce urine output in patients with
diabetes insipidus (DI).[vi]
Chloropropamide to increase the effects
of ADH on the kidney receptor sites. Nonsteroidal anti-inflammatory
drugs (NSAIDs) may sometimes be used to good effect. Lowered salt
intake. Prognosis:
Congenital NDI is a chronic condition requiring life-long treatment.
Advances in molecular genetics have identified over 70 mutations
(x-linked) involving the vasopressin receptor sites including binding,
defects in their synthesis, processing or intracellular transport or
function. Another thirteen mutations have been found to inactivate the
vasopressin-regulated water channel aquaporin-2 (a recessive autosomal
mode of inheritance).
Current
work focuses on using gene therapy to insert the normal gene sequences
to restore function, but that is still far in the future. [vii] Acquired NDI may resolve
of its own accord, or may be a long-term condition. Living
with the DI Dog Unless
the DI was acquired, and the problem resolved spontaneously or with
treatment, keeping a dog with the condition involves making a number of
life-style changes. The first and most immediate change will be to see
that the dog has a continuous supply of drinking water. The second
change will be to see that the dog has a nearby place to urinate. Even
with medication, the urge can come on very suddenly, and in most cases,
the dog will not be able to go more than an hour or so without
urinating. If you do bring a dog in, the housekeeping aspects may be
ameliorated somewhat with a “dog door” leading outside. But, be
prepared for accidents. The
veterinary side lacks the support groups of the human side, where there
is a Diabetes Insipidus Foundation (DiF) [viii] and a Diabetes Insipidus
and Related Disorders (DIARD) Network.[ix].
These are good sources of information concerning how to live with a
child or family member with DI, and thus contain useful information for
owners with DI dogs. The name of DiF’s quarterly newsletter,
“Endless Water” sums up the problem. Easily
cleaned linoleum and urine catching dog beds such as the SleepPee-Time
Beds™ [x]
are useful for small dogs and for medium to large dogs in mild DI cases.
(Editor’s note: the SleepPee-Time Beds ™was previously mentioned in
the October ‘99 issue) A large DI dog can produce 2 gallons of urine
per day. That amount of urine requires special accommodation if the dog
is to be kept in other than a yard or a kennel. The Puppy Go Potty™
may be the answer to this problem. If accidents do happen the stain and
odor remover Get Serious!® has been shown to be very effective.
(Editor’s note: Puppy Go Potty™ and Get Serious!® were previously
reviewed in the December ‘99 issue of Dog World)
[xi],[xii] We
wish to leave you with the thought that without sufficient ADH to
produce normal urine output, or failure of vasopressin receptors to
respond to the ADH levels, or failure of the aquaporins to return fluid
back to the blood, there is nothing that the dog can do to reduce its
urine output. When it has to go, it has to go. That is all there is to
it. This is not a behavioral problem. When traveling with a DI dog, make
frequent stops for urination and drinking. It is very easy to dehydrate
a DI dog, especially on a hot day with
potentially fatal results.
[i] Janet M.
Scarlett, Mo D. Salman, John G. News, Jr., Phillip H. Kass; Reasons for
Relinquishment of Companion Animals in U.S. Animal Shelters:Selected
Health and Personal Issues.Journal of Applied Animal Science, 2(1),
41-57 Back to Pets and DI |