Clinical Pathology Interpretation in

Geriatric Veterinary Patients

Fred L. Metzger, DVMa,*, Alan H. Rebar, DVM, PhDb

KEYWORDS
• Geriatric dogs • Geriatric cats • Laboratory trending • Hematology

KEY POINTS
• Routine monitoring of clinicopathologic data is a critical component in the management of
older patients.
• Serial data evaluations on an individual animal can prove to be a highly objective effective
means of characterizing developing disease.
• The complete blood count provides a broad overview of the general health status of the
patient.
• The minimum canine geriatric database includes the CBC, biochemical profile (with
electrolytes), complete urinalysis.
• The minimum senior feline database includes the CBC, biochemical profile (with electro-
lytes), complete urinalysis, total T4.
• Important geriatric conditions in dogs cats include chronic renal disease, hepatobilliary
disease endocrine metabolic disorders.

INTRODUCTION

Early disease recognition can help improve the quality of life for all dogs and cats, but
especially for older dogs and cats and their owners. Complete diagnostic efforts,
including laboratory profiling, are critical because geriatric pets frequently have
abnormalities in multiple body systems and often receive long-term medications for
chronic diseases or conditions related to aging.
Veterinarians should evaluate serial hematologic and biochemical data on an
individual patient when performing yearly wellness testing and when following the
progression or regression of a disease once recognized. Serial data evaluations on an
individual animal can prove to be a highly objective and effective means of characterizing

The authors have nothing to disclose.

a b
Metzger Animal Hospital, 1044 Benner Pike, State College, PA 16801, USA; Discovery Park,
Purdue University, West Lafayette, IN, USA
* Corresponding author.
E-mail address: [email protected]

Vet Clin Small Anim 42 (2012) 615– 629

http://dx.doi.org/10.1016/j.cvsm.2012.04.004 vetsmall.theclinics.com
0195-5616/12/$ – see front matter © 2012 Elsevier Inc. All rights reserved.
616 Metzger & Rebar

Fig. 1. Yearly creatinine measurements for a geriatric poodle.

developing disease in the clinically normal patient or of objectively determining if

therapy is working appropriately with ill patients.
This article presents a brief review of important hematologic and biochemical
testing parameters and concludes with a synopsis of laboratory findings for several
common geriatric diseases, including chronic renal disease, canine chronic hepatitis,
canine hyperadrenocorticism (Cushing disease), diabetes mellitus (DM), and feline
hyperthyroidism.

TRENDING DATA DURING HEALTH

Serial laboratory data are especially critical in the interpretation of laboratory profiles
in geriatric patients because laboratory data are much more objective and sensitive
than clinical presenting signs or physical examination findings.
Fig. 1 represents yearly creatinine measurements for a geriatric poodle. Not until
year 11 is there a clear increase out of the reference interval. However, in as early as
years 7 through 10, the trend toward increasing creatinine values is observed. This
type of trend should prompt further investigation to more critically evaluate the kidney
(graphic examination of concentrating ability with retrospective serial specific gravity
review, diagnostic imaging of the kidney, urine protein:creatinine ratio measurement,
etc) and institute therapy earlier.

THE GERIATRIC SCREENING PANEL

The minimum canine geriatric database includes the complete blood count (CBC),
biochemical profile (with electrolytes), and complete urinalysis. The minimum senior
feline database includes the CBC, biochemical profile (with electrolytes), complete
urinalysis, and total T4.1
 Geriatric Pathology Interpretation 617

OTHER COMMONLY PERFORMED GERIATRIC TESTS

Primary senior profiling may reveal abnormalities that require further investigation.
More specific geriatric laboratory tests include urinary tract protein evaluation
(microalbuminuria, urine protein:creatinine ratio), hepatic function tests (bile acids and
ammonia tolerance), endocrine assays (serum fructosamine, free T4, canine thyroid-
stimulating hormone, insulin, ionized calcium, parathyroid-like peptide, parathyroid
hormone assay, urine cortisol:creatinine ratio, adrenocorticotropic hormone stimula-
tion, dexamethasone suppression, 17-hydroxyprogesterone), and cardiac markers
(N-terminal prohormone of brain natriuretic peptide [NT pro-BNP]) among others.
This article will focus only on the minimum geriatric database (hemogram, bio-
chemical profile, urinalysis and total T4) and recommends that the reader pursue
additional readings suggested at the end more comprehensive information.

INTERPRETING THE GERIATRIC HEMOGRAM (CBC)

The CBC provides a broad overview of the general health status of the patient. The
peripheral blood serves as the transport medium between the bone marrow and the
tissues; consequently, the CBC provides a snapshot of the hematopoietic system at
a specific point in time. The peripheral blood film examination is especially important
in geriatric patients because erythrocyte, leukocyte, and thrombocyte changes are
common in older patients and may give clues to occult underlying diseases.

Evaluating the Red Blood Cells

Red blood cell (RBC) data include the hematocrit, RBC count, hemoglobin concen-
tration, absolute reticulocyte count, and indices such as mean cell volume, mean cell
hemoglobin concentration, and red cell distribution width.
If RBC mass is reduced, the animal is anemic. The degree of anemia should be
further considered in conjunction with plasma protein concentrations. If protein
concentrations are elevated, then the animal may be dehydrated, and the anemia may
be more severe than RBC mass measurements indicate. Anemia is a common
syndrome detected in senior patients and prompt recognition allows earlier detection
of underlying causes.
Peripheral blood film evaluation may provide important information if red cell
abnormalities such as poikilocytes are identified (abnormally shaped red cells); the
specific type of poikilocyte often proves to be a good indication of specific types of
developing disease.

Regenerative or nonregenerative anemia?

Reticulocytosis is the hallmark and best single indicator of intensified erythropoiesis,
allowing classification of anemias into regenerative or nonregenerative types based
on bone marrow responsiveness.2 The absolute reticulocyte count is the most
objective measure of current bone marrow responsiveness in cases of anemia. If the
bone marrow responds with an increase in RBC production of appropriate magnitude,
the anemia is regenerative (responsive). Common types of regenerative anemia
include blood loss anemia (secondary to any of a number of causes including
bleeding neoplasm) immune-mediated hemolytic anemia, fragmentation anemia
(microangiopathic hemolysis), and occasionally Heinz body hemolytic anemia due to
oxidative injury.
The finding of a bone marrow response and a significant reticulocytosis in the
absence of anemia may be an important early indicator of underlying disease.3 In
some circumstances where RBC life span is decreased and the bone marrow has the
618 Metzger & Rebar

Fig. 2. Spherocytes (S) are spherical erythrocytes that have lost their normal biconcave shape
resulting in more intense staining than normal erythrocytes (N). They have no central zone of
pallor and they appear smaller than normal erythrocytes.

capability of responding, compensation may occur with an underlying finding of

reticulocytosis without anemia. When this is observed, investigation into developing
liver, splenic, renal, and immune-mediated disease and other conditions resulting in
this type of response is warranted.3
Nonregenerative anemias (and in particular the anemia associated with inflamma-
tion and chronic disease) are the most frequently encountered anemias in geriatric
patients because of the increased incidence of chronic renal failure, chronic hepatitis/
hepatopathy, neoplasia, and endocrinopathies.

Important poikilocytes in senior patients

Spherocytes are spherical erythrocytes that have lost their normal biconcave shape,
resulting in more intense staining than normal erythrocytes. They have no central zone
of pallor and they appear smaller than normal erythrocytes (Fig. 2). Spherocytes are
commonly seen with many of the immune-mediated hemolytic anemias encountered
in veterinary medicine. Caution must be used when attempting to identify spherocytes
in feline erythrocytes because feline erythrocytes are much less biconcave in shape
than red cells of dogs and therefore normally have significantly less central pallor.4
Acanthocytes are abnormally shaped erythrocytes, having 2 to 10, blunt, finger-like
projections of varying sizes on their surface (Fig. 3). Acanthocytosis is most
commonly associated with liver disease where lipid metabolism is altered and lipid
loading of red cell membranes occurs. Chronic hepatitis/hepatopathy and hepatic
hemangiosarcoma in dogs and hepatic lipidosis in cats are relatively frequent
causes.4

Evaluating the White Blood Cells

Leukogram data include total and differential white blood cell (WBC) counts and a
description of WBC morphology from the peripheral blood film. Differential cell counts
should always be expressed and interpreted in absolute numbers, not percentages.
All leukocyte compartments—neutrophils and their precursors, lymphocytes, mono-
cytes, eosinophils, and basophils—must be evaluated. Neutrophilic left shifts, per-
sistent eosinophilia, and monocytosis are the best indicators of inflammation.5 Left
 Geriatric Pathology Interpretation 619

Fig. 3. Acanthocytes (A) are abnormally shaped erythrocytes having 2 to 10, blunt, finger-like
projections of varying sizes on their surface.

shifts (increased numbers of immature [band] neutrophils in circulation) indicate

increased turnover and tissue use of neutrophils. Eosinophilias are commonly
associated with inflammatory diseases involving parasitic infestations and hypersen-
sitivity responses. Monocytosis is seen in peripheral blood when there is a demand for
phagocytosis.
Inflammatory leukograms may be present in senior patients for many reasons
including inflammatory processes associated with underlying conditions such as DM,
hyperadrenocorticism, and neoplasia, among others. Persistent peripheral eosino-
philia indicates a systemic allergic or hypersensitivity reaction and may be associated
with feline asthma, systemic parasitic disease, and certain cancers. Some neoplasms,
such as lymphoma, mast cell tumor, and solid tumors, are associated with eosino-
philia caused by tumor cell elaboration of interleukin 5 and other cytokines.6
Persistent marked neutrophilia with no obvious underlying inflammatory process must
be investigated for potential underlying chronic myelogenous leukemia, even when
atypical neutrophil forms are not observed in the peripheral blood.
Lymphocyte evaluation is especially important in senior patients because stress
leukograms may indicate undetected underlying disease including hyperadrenocorticism.
When “atypical” lymphocytes or marked lymphocytosis with “normal” appearing
lymphocytes are identified, investigation into potential underlying lymphoproliferative
disease is warranted. Review by a veterinary clinical pathologist recommended and
possible immunophenotyping or polymerase chain reaction clonality testing may be
warranted.

Evaluating the Platelets

An assessment of platelet numbers is an important part of every CBC. As with RBCs,
the principal issue is whether platelet numbers are normal, increased (thrombocyto-
sis), or reduced (thrombocytopenia).
Transient or intermittent thrombocytosis may be associated with conditions such
as the following: blood loss, fractures, gastrointestinal disorders, drug therapy, and
nonhematologic neoplasias.7 Persistently high platelet counts (sometimes ⬎1 million/␮L)
may be the result of platelet leukemia (essential thrombocythemia) and should be
thoroughly investigated. Essential thrombocythemias may have both platelets and
620 Metzger & Rebar

blasts in circulation. Other hematologic abnormalities (severe nonregenerative ane-

mia, panleukopenia, etc) may also be present as a result of bone marrow replacement
by neoplastic platelet precursors.
Thrombocytopenia is of great clinical significance in any patient. Platelet evaluation
in geriatric veterinary patients is especially important because thrombocytopenia has
been reported in approximately 13% of dogs that have neoplasia, particularly
lymphoma, multiple myeloma, myelogenous leukemia, and hemangiosarcoma.8
Platelet counts below 40,000/␮L can lead to overt bleeding; however, one should
always keep in mind that automated platelet counts may be inaccurate because
variable platelet size and/or platelet clumping can result in falsely low counts,
particularly in cats. Suspected thrombocytopenia should always be confirmed by
looking at a peripheral blood film before pursuing further diagnostics.
True thrombocytopenia can result from 4 mechanisms: sequestration of platelets in
the spleen, increased peripheral use of platelets, peripheral destruction of platelets, or
decreased platelet production.5
Sequestration thrombocytopenia is sometimes seen in cases of hypersplenism in
humans but is rare in animals. Platelet counts are usually moderately reduced.
Consumption thrombocytopenia (increased peripheral use) is seen in association
with severe inflammatory disease and is often a feature of disseminated intravascular
coagulopathy. Again, peripheral platelet counts are moderately decreased. Bone
marrow aspirates contain adequate numbers of megakaryocytes (platelet precursors).
In dogs with disseminated intravascular coagulopathy, red cell fragments (schisto-
cytes) are often seen on blood films.
Destruction thrombocytopenia is caused by antibodies directed against circulating
platelets. Platelet counts can be quite low (⬍50,000/␮L). Megakaryocytes are often
present in increased numbers in the bone marrow. Destructive thrombocytopenias
are often responsive to therapy with glucocorticoids or other immunosuppressive
therapeutic agents.
Production thrombocytopenia is characterized by decreased numbers of bone
marrow megakaryocytes. Peripheral counts may be quite low (often 50,000/␮L or
less). The cause is often obscure, but this condition may result from immune-
mediated marrow disease (antibodies directed against bone marrow platelet precur-
sors) and may also respond to immunosuppressive therapy.

INTERPRETING THE GERIATRIC BIOCHEMISTRY PROFILE

It is beyond the scope of this chapter to discuss every laboratory finding for geriatric
patients. Important geriatric conditions in dogs and cats include chronic renal
disease, hepatobilliary disease, and endocrine and metabolic disorders (Cushing
disease, DM, canine hypothyroidism, and feline hyperthyroidism). Accordingly, here
we will limit our comments to a discussion of the laboratory findings in several of
these important conditions. For more detailed discussions of laboratory profiling in
general, readers should consult the references listed at the end of the article.

EXPECTED CLINICOPATHOLOGIC PATTERNS WITH COMMON GERIATRIC

CONDITIONS
Chronic Renal Disease
Chronic renal disease (CRD) is the most frequently encountered urinary system
disease in geriatric dogs and especially cats. Laboratory profile abnormalities
commonly associated with CRD include anemia, azotemia, hyperphosphatemia,
hyperkalemia or hypokalemia, metabolic acidosis, and isosthenuria.9 More severe
changes are commonly seen with chronic renal failure (CRF).
 Geriatric Pathology Interpretation 621

Hemogram
Anemia is a frequent finding with CRF patients. Underlying mechanisms include
decreased renal erythropoietin production, decreased erythrocyte survival, and
possible uremia-induced gastrointestinal ulceration with blood loss.10 The anemia
associated with CRF is typically mild to moderate and usually nonregenerative. If
bleeding associated with anemia is a prominent finding, some evidence of regener-
ation may be observed.

Biochemical profile
Blood urea nitrogen (BUN) and creatinine (Cr) Azotemia is defined as increased
circulating levels of nitrogenous wastes and is characterized by elevated BUN and Cr
levels. Elevated BUN and Cr are typical in CRF.
BUN and Cr are indicators of glomerular filtration (GFR) rate but do not elevate in
renal disease until more than three-fourths of the nephrons are nonfunctional. Since
BUN can be increased following a high protein diet or bleeding into the gastrointes-
tinal tract, Cr is the superior measure of GFR. BUN and Cr must be interpreted in light
of urine specific gravity. If BUN and Cr are elevated and urine specific gravity is
greater than 1.030 in dogs and 1.035 in cats, then azotemia is most likely prerenal
(resulting from hemoconcentration). If urine specific gravity is isosthenuric (between
1.008 and 1.012, essentially the specific gravity of plasma), then primary renal disease
is suspected. It is important to note that the occasional feline patient may concentrate
urine to greater than 1.040 and still have renal disease.9

Phosphorus Like BUN and Cr, phosphorus is also cleared via glomerular filtration. In
general, elevations in phosphorous levels correlate with Cr elevations.
Phosphorus levels should be closely monitored during treatment for CRF because
chronic hyperphosphatemia may result in renal secondary hyperparathyroidism and
soft tissue mineralization.11

Potassium Potassium is predominantly an intracellular ion so serum potassium levels

do not necessarily reflect total body potassium. Both hyperkalemia (increased serum
potassium) and hypokalemia (decreased serum potassium) can be seen in CRF.
Hyperkalemia is seen in renal failure in association with metabolic acidosis caused
by circulating uremic acids (sulfates and phosphates). In acidosis, hydrogen ions
move into tissue cells in exchange for potassium ions, which migrate from within cells
into blood.
Hypokalemia occurs when total body stores of potassium are depleted due to
decreased renal tubular absorption and increased renal excretion. This is particularly
an issue with CRD in feline patients. When this occurs, serum potassium levels may
be low even in the face of acidosis.12

Total T4
Decreased total T4 levels may be seen as a result of nonthyroidal illness in CKD
patients. Total T4 should always be evaluated in any feline geriatric CRD or CRF
patient because hyperthyroidism may occur simultaneously with CRD.

Urinalysis
Urinalysis is critical to making the diagnosis of CRD but findings may be somewhat
variable depending on the underlying cause of the CRD. The most consistent finding
is isothenuria (urine specific gravity between 1.008 and 1.012, the specific gravity of
plasma). Casts may or may not be present. In true end-stage renal disease, casts are
622 Metzger & Rebar

rare to occasional and are usually granular or waxy in characterization. If the

underlying cause is pyelonephritis, white cell casts may be seen. In this circumstance
white cells and red cells may also be present in the urine. Proteinuria is variable, again,
dependent upon underlying cause of the CRD.

Canine Chronic Hepatitis

Canine chronic hepatitis (CCH) is a group of necrotizing inflammatory diseases of the
liver with variable etiology and clinical history. CCH usually affects middle-age to
older dogs and includes idiopathic chronic hepatitis, copper-associated hepatitis,
and chronic hepatitis in Doberman pinschers among others.13 Chronic hepatitis may
result in hepatic cirrhosis and fibrosis if the underlying disease progresses to
end-stage liver disease. Biochemical profiling is useful in defining the presence and to
some degree the extent of liver and biliary tree involvement; however, liver biopsy is
generally necessary to fully and accurately characterize these disorders.

Hemogram
Hemogram findings are variable depending upon underlying disease. Most cases of
chronic liver disease are characterized by a mild to moderate nonregenerative
anemia. An inflammatory leukogram is a common accompaniment. Acanthocytes
may be present if lipid metabolism is altered.

Biochemical profile
Alanine aminotransferase (ALT) ALT is a cytoplasmic enzyme found primarily in
hepatocytes of dogs and cats. Whenever there is hepatocyte injury in dogs and cats,
ALT will leak into the blood in increased amounts. In general, peak elevations are
reached in about 48 hours after injury. The circulating half-life of ALT is about 48 to
96 hours in dogs (much shorter in cats), so that continual or rising elevations indicate
ongoing injury. A 2-fold increase in ALT caused by a single episode of hepatic injury
can be expected to resolve in 48 to 72 hours.5 In this respect, ALT is an indicator of
acute hepatocellular injury.
It is important to note that ALT is not a liver function test; rather, it is best regarded
as an indicator of the number of hepatocytes undergoing injury or damage at the
same time. The more hepatocytes affected, the greater are the serum ALT levels. This
indicates nothing about the reversibility of the lesion.
In the active phases of liver disease, large numbers of hepatocytes may be
damaged and ALT levels may be quite high, elevating to 10 times the upper end of the
reference interval or higher.13 As disease progresses to the more chronic phase, ALT
levels tend to decline as injured hepatocytes are lost. In end-stage liver disease with
cirrhosis, ALT levels may even be within reference interval limits as a result of
decreased hepatic mass.

Serum alkaline phosphatase (SAP) SAP is a membrane-bound enzyme found at the

bile canalicular surface of hepatocytes. SAP production is induced whenever choles-
tasis occurs. Unfortunately, in the dog, SAP is not found only in biliary system.
Isoenzymes of SAP can also be found in bone, placenta, kidney, and gastrointestinal
tract and there is even an additional isoenzyme specifically induced by high
circulating levels of glucocorticoids (as is seen with Cushing disease) and other
stimuli.12 The degree of elevation of SAP is therefore extremely important to
interpretation in dogs. Elevations of 2 to 3 times above the upper end of the reference
interval are regarded as nonspecific in dogs. Four-fold or greater elevations in dogs
are regarded as indicative of either cholestasis or elevations of the steroid-induced
 Geriatric Pathology Interpretation 623

isoenzyme of SAP.5 These are differentiated by looking for secondary indicators of

cholestasis (urine, serum bilirubin) and the presence of lymphopenia (as a result of
high levels of circulating glucocorticoids) in the CBC.
In most cases of CCH, SAP gradually elevates over time because the cholestasis
resulting from scarring of the liver is progressive. Levels may frequently reach greater
than 5 times the upper end of the reference interval. Keep in mind that elevations in
SAP do not necessarily occur in concert with elevations of ALT; often, hepatocellular
injury has subsided and ALT levels have returned to normal by the time significant
elevations in SAP are seen.

Gamma-glutamyl transferase (GGT) GGT is a membrane-bound enzyme associated

with bile duct epithelium. As such, it is a second primary indicator of cholestasis. It
has been suggested that GGT may be more useful than SAP in dogs since it is not
directly induced by glucocorticoids.14 However, in practice, SAP and GGT tend to
elevate together, even when steroid induction is the underlying cause of the SAP
elevation. This is probably because high circulating levels of glucocorticoids induce a
steroid hepatopathy with hepatocellular swelling and secondary intrahepatic choles-
tasis, which causes the GGT to rise as well.
Canine cases are seen in which GGT is elevated to a greater proportion than
alkaline phosphatase (ALP). Such patients generally suffer from biliary obstruction
and extrahepatic cholestasis.

Total protein and albumin Total protein and albumin may be regarded as liver function
tests. All of the plasma proteins with the exception of the immunoglobulins are
produced by the liver. Consequently, patients with decreased functional hepatic
mass, such as those with advanced CCH, often present with hypoproteinemia with
hypoalbuminemia and normal to increased globulins. These changes are usually only
seen in chronic liver disease primarily because plasma proteins have a long circulating
half-life (7–10 days) and the hypoalbuminemia/hypoproteinemia takes significant time
to develop.

Serum and urine bilirubin Serum bilirubin and urine bilirubin are also often elevated in
CCH, primarily as a consequence of cholestasis. Bilirubin is a normal breakdown
product of hemoglobin. When aged red cells are removed from circulation by
splenic and other tissue macrophages, the heme from hemoglobin gives rise to
unconjugated bilirubin, which is transported by blood to the liver, where it is
conjugated to bilirubin diglucuronide. Normally, the conjugated bilirubin then
passes out of the body with the bile.
Whenever cholestasis occurs, levels of conjugated bilirubin in the blood elevate.
Over time, as liver disease and cholestasis become chronic, circulating levels of
unconjugated bilirubin elevate as well because of decreased hepatic function.
Conjugated bilirubin is water soluble and readily passes through the glomerulus of
the kidney as a part of the glomerular filtrate. Additionally, the ability of canine renal
tubules to reabsorb conjugated bilirubin is limited. As a consequence of these 2 facts,
increased circulating levels of conjugated bilirubin quickly lead to bilirubinuria.12
Bilirubinuria may be recognized before bilirubinemia is detected.
Urine bilirubin and serum bilirubin are generally less sensitive indicators of
cholestasis than are SAP and GGT.

Bun Although BUN is generally used as an indicator of glomerular filtration, it is also

an indicator of liver function. When protein enters the gastrointestinal tract, it is
624 Metzger & Rebar

converted to ammonia, which readily diffuses across the intestinal lining and enters
the portal circulation. The portal circulation carries the ammonia to the liver where it
is converted to urea via urea cycle enzymes. When urea cycle activity is reduced as
a result of decreased functional hepatic mass or congenital or acquired portosystemic
shunt, circulating urea levels may be decreased and circulating ammonia levels may
be increased. Both decreased functional hepatic mass and acquired portosystemic
shunt may be seen with some cases of CCH. A common accompaniment of high
circulating ammonia levels is the potential presence of ammonium biurate crystals in
the urine.

Glucose Low fasting blood glucose levels can also indicate reduced functional
hepatic mass. The liver is central to carbohydrate metabolism and is the principal
site of glycogen storage. When the liver’s capacity to store glycogen is impaired,
hypoglycemia can result. Hypoglycemia in the face of liver disease is a poor
prognostic sign.

Cholesterol and triglycerides The liver also plays a central role in lipid metabolism;
liver disease can therefore profoundly affect circulating lipid levels. In general, liver
disease, particularly when there is a significant cholestatic component, is associated
with hypercholesterolemia and normal triglycerides. However, this pattern is hardly
specific for liver disease and may be associated with conditions such as hypothy-
roidism, Cushing syndrome, DM, and others. Since the liver is the site of de novo
cholesterol synthesis, end-stage liver disease with profoundly decreased functional
hepatic mass can also present with hypocholesterolemia. This finding is less frequent
but actually more specific for liver disease than is hypercholesterolemia.

Urinalysis
Findings most suggestive of liver disease are elevated urine bilirubin and the presence
of ammonium biurate crystals. These were discussed in greater detail earlier.

Liver biopsy
As stated earlier, hepatic biopsy is critical to properly evaluate the canine chronic
hepatopathies. Once profiling has established the presence of liver pathology, biopsy
is warranted. Coagulation panels should be evaluated prior to biopsy as the majority
of clotting proteins are produced by the liver and the potential for bleeding following
biopsy should be assessed.

Canine Hyperadrenocorticism (Cushing Disease)

Canine hyperadrenocorticism (HAC) occurs when the adrenal gland produces excess
adrenal hormones. The clinical signs and laboratory abnormalities are largely the
result of excessive circulating levels of cortisol. The majority of cases are usually the
result of a pituitary tumor (80%– 85%) causing adrenal hyperplasia or a primary
adrenal tumor (15%–20%).13
Most HAC patients are older dogs; clinical signs can be quite variable and include
polyuria/polydipsia, bilateral alopecia, muscular weakness, and pendulous abdomen.

Hemogram
The most common hemogram change is the stress leukogram. (leukocytosis char-
acterized by lymphopenia, mild mature neutrophilia, eosinopenia, and variable mild
monocytosis) and occurs in approximately 80% of HAC patients.14 The most
common hemogram change is the stress leukogram. Steroid hormones stimulate red
 Geriatric Pathology Interpretation 625

cell production so high normal to mildly polycythemic red cell counts are not
uncommon. Mild inappropriate nucleated red cell responses (5–10 nucleated RBCs/
100 WBCs in the absence of polychromasia) and reticulocytosis with a normal HCT to
mild erythrocytosis are also sometimes present.

Biochemical profile
Hepatic enzymes Elevated circulating corticosteroids induce production of a steroid-
specific hepatic isoenzyme of SAP. As a consequence, it is estimated that approxi-
mately 80% of all canine Cushing patients have elevated levels of SAP.15
High levels of circulating glucocorticoids also cause hepatocellular swelling with
vacuolar degeneration (steroid hepatopathy). Steroid hepatopathy is associated with
mild to moderate elevations in ALT as well as elevations in GGT. GGT elevations are
probably secondary to intrahepatic cholestasis.

Glucose Glucocorticoids are gluconeogenic, and Cushing syndrome is commonly

associated with mild to moderate elevations in blood glucose. Values generally fall
between the upper end of the reference interval (⬃120 mg/dL) and the renal threshold
(180 mg/dL).

Total T4
Approximately 70% of dogs with naturally occurring HAC have decreased basal
thyroid levels most likely from chronic elevations in cortisol (nonthyroidal illness).15
Cushing’s patients may have decreased total T4 concentrations from nonthyroidal
illness. Confirmatory thyroid testing (free T4, thyroid-stimulating hormone assay) is
recommended to differentiate thyroidal from nonthyroidal causes.

Urinalysis
Glucocorticoids block anti-diuretic hormone (ADH) receptors in the kidney, thereby
inducing polydipsia and polyuria. As a result, urine specific gravity is often 1.020 or
less. If DM is present, glucosuria with or without ketonuria (ketoacidosis) may be
present. Concurrent urinary tract infection is common in HAC patients; urine culture
and sensitivity should be performed.15

Diabetes Mellitus
DM can have variable presentations in dogs and cats because of the disease
subtypes commonly encountered. Various subtypes include insulin-dependent DM
(frequently referred to as “type 1” and most common in dogs), non–insulin-dependent
DM (also referred to as “type 2” or “insulin resistant” and most common in cats), and,
finally, complicated DM (also referred to as diabetic ketoacidosis).15
It is important to note that cats frequently have stress-induced hyperglycemia,
which can result in glucose concentrations greater than 300 mg/dL and can further
complicate the diagnosis of diabetes in cats.

Hemogram
Hemogram findings are variable depending on the presence of other concurrent
diseases (pancreatitis, Cushing disease, acromegaly, etc), but stress leukograms are
common in systemically ill patients.
DM is the feline disease with the greatest correlation with the presence of Heinz
bodies.16 Cats with DM are frequently nonanemic, but the presence of several Heinz
bodies can result in reduced RBC life span and most patients are not anemic.17
626 Metzger & Rebar

Biochemical profile
Hepatic enzymes Elevated ALT is common with diabetes because of hepatocellular injury
due to fatty change. Swelling of fat-laden hepatocytes leads to secondary intrahepatic
cholestasis and elevations in SAP and GGT. SAP elevations are less striking in cats than
in dogs because of the very short half-life of SAP in cats. In cats, proportionally higher
elevations in SAP than GGT are highly suggestive of hepatic lipidosis.

Glucose Fasting hyperglycemia is present and often profound with glucose values
frequently greater than 400 mg/dL. In dogs, fasting levels of greater than 180 mg/dL
are diagnostic. In cats, because of the existence of stress hyperglycemias of greater
than 300 mg/dL, diagnosis is more difficult and requires demonstration of fasting
elevations when the patient is in an unstressed state. Finding ketones in urine is also
helpful. Serum fructosamine values may be very elevated and therefore helpful in
making the diagnosis in cats.

Fructosamine Serum fructosamine concentrations are used on diabetic patients as a

marker of mean blood glucose concentrations during the preceding 2 to 3 weeks. The
higher the average blood glucose concentration over this time, the higher is the serum
fructosamine concentration, and vice versa.
Results for fructosamine may be increased up to 150% by the presence of
hemolysis, so careful blood collection technique and sample handling are required.
Normal (nondiabetic) serum fructosamine reference intervals18:
Canine: 260 –378 ␮mol/L
Feline: 191–349 ␮mol/L

BUN and creatinine Azotemia occurs relatively frequently especially with severely
dehydrated patients. This prerenal azotemia is characterized by a concentrated urine
specific gravity in conjunction with elevations in BUN and Cr.

Potassium As mentioned previously, because potassium is primarily an intracellular

ion, serum potassium levels do not necessarily reflect total body potassium. Either
hyperkalemia or hypokalemia can be seen in diabetics, depending on the metabolic
state of the patient at the time of sample collection.
Hyperkalemia occurs with insulin deficiency because insulin is required to move
potassium into cells. Furthermore, hyperkalemia is a common feature of acidosis,
because, in acidosis, hydrogen ions move into cells in exchange for potassium ions,
which move into the extracellular space (plasma). Thus, as unregulated diabetics
become ketoacidotic, their hyperkalemia is exacerbated.
In long-standing DM, there is osmotic diuresis as a result of glucosuria. The
osmotic diuresis also causes increased excretion of potassium, which may eventually
result in total body potassium depletion. Therefore, in unregulated diabetics, hypo-
kalemia can actually occur in the face of ketoacidosis. This can be a life-threatening
event and potassium supplementation is required. Serum potassium must also be
closely monitored during the routine treatment of diabetics. Regardless of the state of
total body potassium balance at the time, treatment with insulin drives potassium
intracellularly, making potassium supplementation essential.15

Phosphorus Hyperphosphatemia is seen as an accompaniment to azotemia in

diabetics. Furthermore, severe hypophosphatemia may develop as a serious compli-
cation to diabetic ketoacidosis patients and result in hemolytic anemia, which can be
life-threatening.18
 Geriatric Pathology Interpretation 627

Urinalysis
Glucosuria and ketonuria are common occurrences in uncontrolled diabetics. Keto-
nuria may be accompanied by a metabolic ketoacidosis (increased anion gap in the
peripheral blood), which may be life-threatening. Concurrent urinary tract infection is
possible secondary to glucosuria. In these instances, white cells and red cells may be
present in increased numbers and bacteria may be seen. Urine culture and sensitivity
should be performed.

Feline Hyperthyroidism
Feline hyperthyroidism is a multisystemic metabolic disease and is the most common
endocrinopathy in older cats. Hyperfunctioning adenomatous hyperplasia of the
thyroid gland results in a variety of clinical signs and laboratory abnormalities. Thyroid
evaluation (total T4) should always be performed when evaluating the laboratory
profiles of geriatric felines.

Hemogram
Slight polycythemia is found in more than 50% of hyperthyroid cats and macrocytosis
may cause an elevation in the mean cell volume.19 Heinz bodies in the absence of
hemolytic anemia may be seen.

Biochemical profile
Mild to marked increases in the serum activities of many liver enzymes, including ALT
and ALP are the most common and striking biochemical abnormalities of feline
hyperthyroidism.20 Elevations in hepatic enzymes and T4 concentrations are related,
with liver enzyme abnormalities being more common in cats with severe hyperthy-
roidism. Although how thyroid hormone excess stimulates the high ALT and SAP
activity is not completely understood, it is clear that these high liver enzymes return
to normal upon successful treatment of hyperthyroidism.21
Mild to moderate azotemia occurs occasionally in hyperthyroid cats. Renal function
should be closely monitored because increased cardiac output associated with
elevated thyroid hormone levels may mask reduced glomerular filtration.

Total T4
The majority of hyperthyroid patients have elevated total T4 concentrations, which
confirm the diagnosis in cats with compatible clinical signs. Total T4 may be within the
normal reference interval in patients with concurrent hyperthyroidism and nonthyroi-
dal illnesses (chronic renal failure, diabetes, etc). Confirmatory thyroid testing (free T4,
T3 suppression test, thyroid radionucleotide imaging) is recommended in cats with
signs compatible with hyperthyroidism but normal total T4 levels.

Urinalysis
Urinalysis is usually unremarkable but patients should be monitored for evidence of
decompensating renal function when treatment for hyperthyroidism is initiated.

SUMMARY

Routine monitoring of clinicopathologic data is a critical component in the manage-

ment of older patients because blood and urine testing allows the veterinarian to
monitor trends in laboratory parameters which may be the early indicators of disease.
Laboratory profiling often provides an objective and sensitive indicator of developing
disease before obvious clinical signs or physical examination abnormalities are
628 Metzger & Rebar

observed. The primary key to the power of this evaluation is that the data is collected
year after year during wellness checks and is examined serially.
Chronic renal failure, chronic active hepatitis, canine hyperadrenocorticism, diabe-
tes mellitus and feline hyperthyroidism were reviewed and expected laboratory
findings were summarized.
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