Case report: Five year old rabbit that suffers from chronic hypoalbuminemia and hyperglycemia

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Abstract
Lucky is a male gray spotted lop that has a complete butterfly coloring around his nasal region and relatively colored fur. He was neutered at young age. He started to suffer from problems with his eyes and lacrimal duct, prior to developing metabolic problems.
1 Figures
Case report: Five year old rabbit that suffers from
chronic hypoalbuminemia and hyperglycemia
Valerie Nagy and Esther van Praag
Lucky is a male gray spotted lop that has a complete butterfly coloring around his nasal
region and relatively colored fur. He was neutered at young age. He started to suffer
from problems with his eyes and lacrimal duct, prior to developing metabolic problems.
Lucky is a mini lop rabbit that was
purchased from a pet store (Figure 1). He
was born in August 2008 and castrated a
few months later. As an adult, he weighs
about 3.5 kg (7.7 lbs.) (Figure 2). Lucky is a
nervous rabbit that reacts strongly to stress:
shaking and fast breathing. This is especially
the case when his cage is cleaned, when
brushed and during the treatment of his
runny eyes. Apart from this nervousness,
Lucky is a healthy rabbit during the first
years of his life, with the exception of stasis
problems of the digestive system once a
year. He lives in a big cage, but is free to
Figure 1: Lucky, a spotted lop rabbit suffering from several health problems, here in company of his
partner Hunny.
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run outside for a minimum of 8 hours per
day. Despite a healthy diet, Lucky gained
weight until the age of 6, after which he
suddenly lost 0.5 kg (1.1 lbs.) and weighed
2.75 kg (6 lbs.) towards the end of his life,
at the age of 7 (Figure 3). This loss of
weight is accompanied by a
decrease in appetite and a
decrease in the size of solid
fecal droppings. His coat in his
face became rough looking
because of the cleaning twice a
day. The rest of his coat was
smooth.
Ear Infection
Chronic otitis is more
common in lop rabbits, as
proper aeration of the outer ear
canal is hindered by the falling
ears. A surgical option is the widening of the
entrance of outer ear canal, but results have
not been as good as hoped in many rabbits.
Lucky suffered from a chronic infection of
the external portion of the ear canal. The
culture of a sample showed the massive
Figure 2: Lucky is overweight in June and remains so a year later, in 2014, in spite of a strict and
healthy diet.
Figure 3: Lucky after losing weight.
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presence of bacteria (+++) and, to a lesser
extent, yeast (++). This condition was
treated with a suspension of gentamycin,
and Tris-EDTA, and penicillin injections
every third day.
The infection was successfully treated.
Respiratory problems
Lucky suffered from an infection of the
upper respiratory system. The culture of a
nasal sample revealed the presence of
coagulase negative staphylococcus.
Lacrimal duct and icterus
Lucky begins to suffer from persistent
watery eyes (epiphora) and the presence of
a thick mucus or white-colored discharge in
the right eye, following by the left eye later
at the age of 2 (Figure 4). It seems to be
related to an infection of the nasolacrimal
duct. The cause is unknown. It may relate to
a slight bone deformation that compressed
the duct, a scar from a traumatic event, or it
may be congenital. X-rays did not reveal the
presence of a skull anomaly, bone loss or
dental disease.
Excoriation of the skin with inflammation
of the dermis is observed around the
internal cantus of the right eye (Figure 4).
The lacrimal duct of each eye is flushed at
regular intervals, without success.
Numerous antibiotic treatments are
administered and attempts to irrigate the
nasolacrimal canal have all remained
without success.
An ulcerous lesion with the formation of
scar tissue was present on the surface of the
cornea. It was accompanied by a
neovascularization in the white sclera of the
eye, which, therefore, had a reddish
Figure 4: Irritation of the skin around the inner canthus of the eye, caused by a chronic lacrimation
refractory to any attempted treatment with antibiotics or flushing.
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coloration. Lucky also suffered from injected
sclera, meaning that blood has accumulated
in the white part of the eye. Injected sclera
can be caused by a chronic high level of
glucose, a problem Lucky suffered from all
his life.
Later in his life, the sclera of the eye took
an off-white/yellowish coloration (icterus). It
is usually caused by an accumulation of
bilirubin. Bilirubin is a red-yellow pigment in
urine and blood and bile, and results also
from the degradation of hemoglobin in red
blood cells. The blood test shows that
bilirubin in his blood is normal, but this is
not conclusive.
Itchy burning skin
Disorders of the thyroid gland can induce
an itchy skin. In humans, patients suffering
from thyroid disorders mention a feeling of
tightness in the throat as well as pain and
tenderness on the front of the neck and/or
thyroid area.
With Lucky, he started to pull fur out of
one spot on his chest directly below his
neck. It seemed like an obsession or
something was bothering him (Figure 5).
Could he have experienced these side-
effects of thyroid disease too ? His blood
panel indicates dysfunction of this gland at
the end of his life.
Echography and medical imaging
At the age of 4 years, x-rays of the skull
were taken (Figure 6). They do not show
abnormalities in the skeleton such as a
decrease in bone density or dental problems
that may lead to compression of the
nasolacrymal duct.
At the age of 6, an ultrasound of the
thorax was performed to exclude any
problems in the chest and of the heart
Figure 5: Lucky would pull fur out of one spot on his chest directly below his neck. It seemed like an
obsession or something was bothering him. Right: detail of the fur pulling in his neck.
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before a small surgical
procedure. No anomalies
were observed.
An important blood
component: albumin
Albumin is one of the
three protein compo-
nents present in the
blood and also the main
one (60%). The other
two are globulins and
fibrinogen. Albumin is a
protein that is very
soluble in water. It
plays an essential role
in the proper
functioning of the body
and is a marker of the
general nutritional
status. It also promotes
the transfer of nutrients
and wastes to and from
the blood and cells. It
plays further important
roles, including:
- Transport of
hormones, e.g. the
active T3 form of the
thyroid hormone.
- Transport of
endogenous
substances, e.g.
divalent cations (Ca,
Zn). The binding of
albumin with sodium
ions Na+ enables to
attract fluids into the
blood vessels. The
binding of albumin
with free radicals, free
fatty acids, bilirubin
or bacterial toxins
reduces the toxicity of
these molecules.
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- Transport of drugs via the blood
circulatory system throughout the body.
- Transport of exogenous substances such
as drugs, e.g. antibiotics (penicillin’s
cephalosporin’s, sulfonamides,
tetracyclines), anti-inflammatory
analgesics (salicylic acid, ibuprofen),
sedatives (phenobarbital, diazepam),
certain drugs for cardiac, renal or
nervous system problems, and diuretics.
- Neutralization of free radicals and toxins.
- Activation of blood platelets and transport
of coagulation factors.
- Maintenance of the oncotic pressure
within blood vessels.
- Maintenance of the fluid balance between
the blood and the blood vessels and the
interstitial fluid present between the
blood capillaries and the cells.
- Maintenance of fluids in the blood vessels
or passage of fluids from the blood to the
tissue cells by regulating the speed and
volume of exchanged fluids.
Moreover, the degradation of the albumin
in inflamed tissues will supply them with the
necessary amino acids, fatty acids and the
zinc for their healing.
Endogenous albumin is produced in the
liver only. Its production depends on a
supply of nutrients and nitrogen from the
diet. In humans, a nutritional intake is also
possible with milk or eggs. While hepatocyte
cells bordering the blood vessels free the
synthesized albumin directly into the
bloodstream, most of the albumin is
transported by transcytosis.
The production of albumin in the liver is
regulated according to the needs in the
body. Synthesis of this molecule in hepatic
cells is stimulated by a low level of albumin
in the blood and by the hormones like
cortisol (cortex of the adrenal gland),
thyroxine (thyroid), and by growth
hormones. The presence of toxic molecules
in the liver, potassium and stress also
influence the production of albumin. The
production of albumin in the liver is inhibited
when:
- The liver is not working properly,
- The diet is deficient in amino acids,
- The intestine badly absorbs proteins
and/or amino-acids.
- Renal function is insufficient.
In such cases, administration of albumin
may be considered.
A low level of albumin
(hypoalbuminemia) in the blood is often
associated to protein malnutrition or high
glucose/diabetes, among others. In the case
of protein malnutrition, the pancreas may
fail to produce enough enzymes that will
degrade protein in the intestine. If proteins
are not degraded, the intestine will fail to
absorb them into the blood circulation.
Hypoalbuminemia leads to a deficient
transport of substances, including drugs. In
a healthy being, bilirubin, which is produced
by the degradation of hemoglobin, will bind
to albumin and be transported to the liver to
be detoxified. When this is not possible,
bilirubin becomes toxic. Bilirubin also
competes with therapeutic molecules in the
blood. If the latter no longer binds to
albumin and circulates freely in the blood,
side effects or even toxic effects may
appear.
A high level of albumin in the blood is
rare. It occurs in case of dehydration or is
linked to the presence of a high level of
thyroid hormone in the blood.
Reference values of serum proteins in a
healthy rabbit:
- Albumin: 25-40 g/l
- Globulin: 1.5-3.3 g/dl or 25-40 g/l
- Albumin-globulin ratio: 0.7-1.89
- Protein total: 50-75 g/l
- Bilirubin- total: 3.4-8.5mol/l or 0-0.75
g/dl.
- Plasma: 44-71 g/l.
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Analysis of the blood tests results
4 years old (August 2012)
A blood panels shows a few values that are
off.
CBC: Slightly elevated hemoglobin
Low heterophils (neutrophils)
The slightly elevated hemoglobin is unlikely
to be related to any condition of concern or
it may be linked to the respiratory disease of
Lucky.
Low heterophils are typically observed in
cases of vitamin deficiency, of infection or
autoimmune disease, of myelodysplastic or
bone marrow disease, or splenomegaly.
Blood enzymes: ALT: normal (54 U/L)
ALP: elevated (78 U/L)
Healthy values are:
Alanine transaminase (ALT): 25-65 U/l
Alkaline phosphatase (ALP): 10- 70 U/l
Aspartate aminotransferase (AST): 10- 98
U/l
Chemistry: Phosphorus: low (3.7mg/dL)
Calcium: normal (15.1 mg/dL)
Glucose: elevated (256 mg/dL)
A low phosphorus level is observed in case
of vitamin D deficiency, in malnutrition,
hypercalcemia (calcium level is normal here)
or an overactive parathyroid gland.
A high level of serum glucose in rabbits is
often caused by the stress of manipulation
during the physical examination by the vet.
Lucky is overweight in spite of a healthy
diet. He shows a chronic elevated level of
glucose in all the blood tests, which hints to
a more severe problem: a diabetes type of
problem.
4 years and 10 months old (June 2013)
REMARK: the white of Lucky’s eyes is
slightly yellowish colored.
A new blood panels is done.
CBC: slightly low hemoglobin
Blood enzymes: ALT: normal (54 U/L)
ALP: normal (37 U/L)
AMY: normal (115 U/L)
ALT and ALP indicate a normal liver function.
Amylase (200-500 U/l) reflects the
pancreatic activity. No blockage or
inflammation, which leads to an increased
level of this enzyme. It is normal. With
normal pancreas and liver values, could
Lucky suffer from a problem with his
gallbladder ?
Chemistry: Albumin: low (2.0 g/dL)
Globulin: high (5.0 g/dL)
ALB/Glob = 0.4 (low)
Glucose: high (369 mg/dL)
BUN: normal (15 mg/dL)
Creatinine: normal (1.4 mg/dL)
Albumin is a marker of the general
nutritional status and is usually associated
to protein malnutrition, hypothyroidism,
and/or a high level of glucose/diabetes,
among others. In the case of protein
malnutrition, the pancreas may fail to
produce enough enzymes that will degrade
protein into amino-acids in the intestine. It
may also hint to an intestinal malfunction,
with an inability to absorb proteins and
amino-acids into the blood circulation.
An elevated level of globulins is usually
associated to a chronic inflammatory
disease. It may be the chronic ear infection,
but may also hint an inflammatory problem
in the intestine.
Glucose is high.
Kidney parameters are normal.
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5 years and 9 months old (May 2014)
Many parameters are suddenly off.
CBC: Low heterophils (neutrophils)
High monocytes
High eosinophils
Heterophils (also called neutrophils in
rabbits) are low, usually the sign of an
infection or a nutrient/vitamin deficiency in
rabbits.
Monocytes are high, usually a sign of
chronic inflammation, possibly of fungal
origin, the presence of parasites or a
problem of the gastrointestinal system.
Eosinophils are high, possibly the presence
of parasites, a skin issue or a gallbladder
inflammation.
Blood enzymes: ALT: elevated (78 U/L)
ALP: elevated (75 U/L)
AST: normal (27 U/L)
AST is normal, while ALT and ALK are
elevated.
Elevated ALK and ALT only is typically
observed in case of bile duct, or gallbladder
dysfunction. If the blockage is partial, there
is often no rise in bilirubin in the blood
serum. The blockage can be caused by a
mass (cancer or benign) or stones.
(Fatty liver is ruled out; this condition is
accompanied by normal values for AST and
ALT).
A failure of the gallbladder and an impaired
bile flow will affect the pancreas and
intestine.
Chemistry: Albumin: high (5.1 g/dL)
Globulin: high (2.7 g/dL)
ALB/Glob = 1.8
Phosphorus: low (3.3 mg/dL)
Glucose: high (348 mg/dL)
Calcium: high (17.1 mg/dL)
Sodium: high (182 Eq/dL)
Chloride: high (129 Eq/dL)
BUN: normal (24 mg/dL)
Creatinine: normal (1.2 mg/dL)
Albumin is suddenly high, an indicator of
dehydration mainly, while globulins are low.
The latter is often indicative of inflammatory
bowel disease. As for low proteins, it may
also indicate protein malnutrition
The level of several serum electrolytes
are off, indicating dehydration or a
dysfunction of the thyroid or the parathyroid
gland.
Analysis of the blood panel results
The low levels of albumin during the last
years of Luckys life tend to indicate that he
suffered from chronic protein malnutrition. A
congenital intestinal problem with poor
absorption of proteins and amino acids or a
failure to produce enough proteins
degrading enzymes by the pancreas ?
Or both ?
Lucky is a spotted rabbit, though rather
colored and with a complete butterfly
around his nasal region. These rabbits
usually do not suffer from megacolon. Yet,
the raised level of globulins may hint a
chronic intestinal inflammation. Could it be a
form of megacolon leading to nutrient
deficiencies ?
The failure to degrade protein properly by
pancreas enzymes leads to poor absorption
of amino-acids in the intestine. The amino-
acids methionine and cysteine in particular
are needed to form insulin in the pancreas.
When these amino acids are low, insulin
production will be low. This may explain the
chronic high levels of glucose observed in
the Luckys blood.
Protein malnutrition is associated to a
change in fur in rabbits: sparse and loss of
its normal sleek and shiny appearance
(Figure 7).
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Gastrointestinal malabsorption of
nutrients may also be the result of an
overactive thyroid or parathyroid gland. The
latter is associated to nervousness. Although
Lucky has always been a nervous rabbit, it
does not allow to conclude that he suffered
from hyperthyroidism in the early years of
his life already. It is only at the end of his
life that abnormal serum electrolyte values
hint to parathyroid gland hyperactivity. The
cause of this hyperactivity is unknown.
The liver parameters (normal AST,
elevated ALT and ALK) are indicative of a
gall bladder dysfunction, e.g. a blockage or
the presence of gallbladder stones. This was
accompanied by the somewhat yellowish
coloring of the sclera in his eyes. Both
gallbladder and parathyroid gland may be
associated. Indeed the parathyroid gland is
involved in the calcium
metabolism. When this
gland is hyperactive,
the level of calcium in
the blood increases.
An increased level of
calcium in the blood
may lead to the
formation of gallstones
in the gallbladder. The
icterus in his eyes
tends to indicate that
the gall-bladder
blockage may have
been present already
before the elevation of
serum calcium.
References
Chen WH, Yu CC, Wu CC, Jan YJ. Eosinophilic
cholangitis with obstructive jaundice
mimicking bile duct carcinoma. J Hepatobiliary
Pancreat Surg. 2009;16(2):242-5.
Cooper DS, Kaplan MM, Ridgway EC, Maloof F,
Daniels GH. Alkaline phosphatase isoenzyme
patterns in hyperthyroidism. Ann Intern Med.
1979 Feb;90(2):164-8.
Lazarus SS, Volk BW. Electron microscopy and
histochemistry on rabbit pancreas in protein
malnutrition Experimental Kwashiorkor). Am J
Pathol. 1964;44:95-111.
Siddique A, Kowdley KV. Approach to a patient
with elevated serum alkaline phosphatase.
Clin Liver Dis. 2012;16(2):199-229.
Volk BW, Lazarus SS. Rabbit Pancreas in Protein
Malnutrition (Experimental Kwashiorkor) and
after Cortisone Administration. Am J Pathol.
1960;37(2):121-35.
Figure 7: A rabbit on deficient diet for 14 weeks. The animal is markedly
undersized. The fur is somewhat sparse and has lost its normal
sleek and shiny appearance. Reprinted from: Volk BW, Lazarus
SS. Am J Pathol. 1960;37(2):121-35.
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