Diagnosing and managing common age-related problems in older dogs and cats (Proceedings)

Aging in dogs and cats is associated with gradual and progressive deterioration in the delicate body systems that eventually results in anatomical changes and decreased physiological functions. At some stage in the progressive decline, a "tipping point" is reached, where all of the physiological reserves are exhausted resulting in altered biochemical parameters; overt changes in diagnostic screening tests; and/or the onset of clinical symptoms of age-related disease occurs. These measurable points are referred to as "benchmarks" of aging. Usually these slowly progressive organ system changes are subtle; undetected by the owner or miss-interpreted by the owner, until the patient is stressed by an unrelated illness, boarding, medications or general anesthesia. Increasingly, those benchmark changes are being routinely identified on senior wellness screening tests, further validating the value of such standardized testing protocols.

Decisions regarding specific drug therapies, anesthetic protocols, pain management strategies, and quality of life issues hinge on the variety of declining physiological "benchmarks." A knowledge and clear understanding of the level of physiological decline of each organ system dictates how an individual patient is best managed. In addition to a complete history and age-related physical examination, the assessment of the level of physiological decline in each organ system requires diagnostic evaluations. Accurate interpretation of a patient's urinalysis, hematology and biochemistry

panels results in data used to aid in the diagnosis, prognosis and treatment of various conditions. Combined with appropriate imaging techniques and other advanced diagnostics presumably will facilitate early identification of both physiological decline and various pathological states. Three gerontology reference books one should consider for their library include J. Hoskins, Geriatrics and Gerontology of the Dog and Cat, 2nd ed.; the Veterinary Clinics of North America, 2005 Geriatrics Ed; and U. Mohr; W.W. Carlton; D. L. Dungworth, Pathobiology of the Aging Dog (vol. 1 & 2).

The generalized changes associated with aging include dryness of all tissues, progressive degeneration of organ function, tissue hypoxia, cellular membrane alterations, decreased enzyme systems, decreased immune competence, and definite personality alterations.

The TEN most common causes of death in older dogs, based on a study funded by the Morris Animal Foundation for Animals, are cancer, cardiovascular disease, renal failure, epilepsy, hepatic diseases, bloat, diabetes, stroke, Cushing's disease, and immune mediated disease. The ten most common causes of death in older cats are cancer, cardiovascular disease, renal failure, diabetes mellitus, FIP, FIV, FeLV, hyperthyroidism, liver and infections. Knowledge of the early warning signs of the 10 most common life threatening diseases in the elderly pets alerts the owner and staff of impending health threats in a timely manner. In addition the list is helpful in determining what specific tests should be included in your "Senior Care" health screening program.

Thermoregulation alterations

Effective thermoregulation (heating and cooling) is deceased in the aging dog. Their decreased ability to pant, decreased cardiac output, combined with ineffective vasodilatation make older pets more prone to heat stroke. Conversely, older patients are also more susceptible to cold ambient temperatures. This age-related cold intolerance is attributed to a decreased basal metabolic rate, decreased cardiac output, decreases in peripheral vaso-constriction, plus less subcutaneous fat in many cases. Cold intolerance can also be a predominant sign of hypothyroidism long before skin and hair coat changes. The resulting response to "cool ambient temperatures" may manifest as behavioral issues including reclusiveness, trembling, and reluctance to go outside for eliminations, and/or sleep cycle disturbances. In addition to suggested environmental changes and thyroid evaluation, warm bedding and outdoor garments may help alleviate some of the abnormal behavior while increasing the animals well being.

Muscle mass loss

Loss of muscle mass and function is inherent to aging! Progressive loss of muscle mass is a normal finding in the older pet. This change is related to a combination of inactivity (disuse) combined with a decrease in muscle cell numbers due to fibrosis, atrophy, and decrease sensitivity to ATP. Atrophy of the semimembranosus, semitendenosis, biceps femoris and quadriceps are most obvious. Skeletal muscles act as the body's long term amino acid (AA) reservoir for body tissue protein synthesis. Occasionally, additional muscle atrophy can also be attributed to decreased dietary protein from lowered protein "prescription" diets. When faced with insufficient dietary essential amino acids, the patient is forced to catabolize their protein store reserves; primarily skeletal muscle. Unfortunately this iatrogenic muscle wasting may be responsible for or may exaggerate any hind limb weakness or lameness already present. The resulting difficulty climbing stairs, jumping, or difficulty rising may be confused with the symptoms of arthritis with the corresponding disuse atrophy. In dogs, an increased dietary protein (essential amino acids); combined with a sensible exercise program; plus the use of anabolic steroids in extreme cases, has been advocated in management of the generalized muscle weakness and muscle wasting conditions regardless of the cause. Although the research is lacking, the use of creatine / phosphocreatine supplements may also be indicated in "rescuing" wasting muscles.

Gastrointestinal decline

Oder dogs often have impaired swallowing reflexes that results in aerophagia with subsequent increased in belching and or flatulence. In addition, many older patients have decreased gastrointestinal motility, decreased gastric acid secretions, decreases in digestive enzymes, and decreased absorptive capacity may be found in the older patient. The normal loss of olfactory neurons combined with the loss of taste buds decreases the palatability of most foods. A picky appetite may result. A lack of sufficient saliva to aid in swallowing dry food can also contribute to a deceased appetite in the "healthy" older pet. The decreases gastric mucosal protective factors, makes the older pet much more susceptible to GI erosions and ulcerations.

Renal decline

The functional unit of the kidney is the nephron. The aging kidneys have a decreased renal blood flow, decreased glomerular filtration rate and decreasing ability to concentrate their urine. As nephrons are progressively lost for various reasons, specific physiological / biochemical benchmarks that can be used to "chart" the progression of chronic progressive renal disease in most patients. The renal system has aging structural changes that may not be clinically evident in the early stages. A loss of 50% of functional nephrons is not unusual in older animals; however, that degree of nephron loss cannot be easily detected. Advancing progressive renal nephron loss can be "guess-timated" by profiling the urinary system; i.e. evaluating the urine specific gravity, the BUN/ Creatinine levels, and in some cases persistent micro-albuminuria. Trending is the concept of repeated monitoring / charting of a biological parameter in that is helpful in "predicting" the patient's future health status. Periodic baseline testing is helpful in "trending" the patient's renal function.

Proper assessment of the urinary system function involves an accurate history (estimated water consumption / urine output when possible), a complete physical examination, complete urinalysis (specific gravity, chem stix, and sediment examination), and serum chemistries. Depending on the specific case and initial laboratory findings, microbial cultures and imaging may also be indicated. A common mistake is failure to evaluate the entire urinalysis, thus missing important information. Uncovering chronic progressive renal disease is often difficult in the very early stages; however there are specific physiological / biochemical benchmarks of the progression insufficiency.

Urine specific gravity;

Once more than 66% of renal function is lost, the patient will lose the ability to concentrate their urine with a corresponding increases in water consumption (PU/PD). Polyuria: Dogs > 45ml/kg/day; Cats >40ml/kg/day Polydipsia: Dogs > 90 ml/kg/day; Cats >45 mls/kg/day. Generally the best urine samples for analysis are morning samples (reflecting maximum concentration) taken by cystocentesis.

Bun and creatinine

Significant decreases in GFR are most easily detected with serum BUN and creatinine levels. However both tests are considered "insensitive" indicators of GFR in chronic renal disease because approximately 75% of functional nephrons must be lost before elevations of either are detected on a chemistry profile. Dietary protein is the primary source of blood urea nitrogen (BUN). Ingested protein is converted to ammonia by bacteria in the gut. The ammonia diffuses across the gut wall into the portal circulation and is carried to the liver. In the liver, ammonia is converted to urea.

Minor elevations in BUN can be caused by high protein diets and gastrointestinal hemorrhage (NSAIDs / Steroid use). Major increases will be associated with a significant decreased GFR (Pre-Renal) i.e. dehydration, congestive heart failure, hypotension, and significant renal disease. Conversely decreased BUN is often an indicator of chronic liver or maldigestion/ malabsorption. Decreased BUN levels also occur when ammonia produced in the gut bypasses the liver as in both congenital and those acquired porto-systemic shunts seen in older animals.

Creatinine is a by-product of muscle metabolism and is excreted exclusively by renal glomerular filtration. Creatinine is a more accurate indicator of the GFR than BUN because it is not affected by the patient's diet, renal tubular reabsorption, protein catabolism or hepatic function. In chronic progressive renal disease, sequential serum creatinine measurements are a better prognostic tool than BUN in chronic progressive renal disease. It is important to note that unlike BUN levels, creatinine levels are not affected by the lowered protein diets. A patient to a lowered protein diet will demonstrate a lowered serum BUN levels despite the fact there has been no actual improvement in renal function.

The serum phosphorous is also excreted by glomerular filtration. Therefore, a reduction in GFR due to pre-renal, renal or post-renal causes produces a delayed but parallel increase in serum phosphorus levels. Therefore, hyperphosphatemia frequently accompanies azotemia especially in advanced cases when GFR or functional nephrons are reduced by 85%.

In chronic progressive renal disease; once more than 66% of renal function is lost, the patient losses the ability to concentrate their urine with a corresponding increases in water consumption. The BUN/creatinine starts to rise (azotemia) after more than 75% renal function is lost. With the remarkable adaptation of nephron in slowly progressive renal disease, the patient can survive and a very small percentage of kidney tissue. Once only 15% of the functional nephrons are left, does the animal become uremic; anorexia, nausea, and vomiting. This baseline testing is also helpful in "trending" the renal function.

Hepatic decline

Geriatric patients can have a decrease in liver mass of up to 50%, which leads to decreases in liver function and available hepatic enzymes for metabolism and detoxification. The age-related decreases in cardiac output result in decreased blood flow to the liver with subsequent decreases in coagulation factors, plasma proteins and serum glucose. Fatty infiltration of the hepatocytes and nodular hyperplasia NH are the two most common age-related lesions in the canine liver. Each could be causes for the mild elevations in serum alkaline phosphatase (ALP) commonly found in older dogs.

The liver performs a wide variety of different and seemingly unrelated functions. It is important in plasma protein synthesis (including coagulation factors), carbohydrate (glucose) metabolism, lipid metabolism, bilirubin metabolism, BUN formation, bile synthesis, plus detoxification of various substances. Biochemical profiling of the liver entails assessments of the liver enzymes, i.e., serum alanine aminotransferase (ALT), ALP and serum gamma glutamyl transferase (GTT), and the various (indirect/secondary) liver function tests, i.e., BUN, glucose, total protein, cholesterol, and fibrinogen. Often there is no direct correlation between liver function, the degree of enzyme elevation, and the prognosis. Pre/post prandial bile acids are considered the definitive liver function test.

Profiling the liver

The liver performs a wide variety of different and seemingly unrelated functions. It is important in plasma protein synthesis (including coagulation factors), carbohydrate (glucose) metabolism, lipid metabolism, bilirubin metabolism, BUN formation, bile synthesis, plus detoxification of various substances. Biochemical profiling of the liver entails assessments of both the liver enzymes and various liver functions and function tests. Often there is no direct correlation between function, the degree of enzyme elevation, and the prognosis.

Serum alanine aminotransferase (ALT) is probably the most reliable indicators of liver problems in small animal patients. However ALT is an indicator of increase membrane leakage and/or hepatocyte injury and not a liver function test. Since ALT is a liver-specific enzyme present in high concentrations within the hepatocytes, any hepatic insult (mild to severe necrosis) may result in an increased ALT. It is important to note that the degree of elevation does not correlate with the actual severity of hepato-cellular damage but rather with the number of hepatocytes involved. After a single insult, maximal ALT levels are reached within 48 hours. The half-life of ALT is approximately 2 to 4 days in the dog and approximately 6 hours in the cat. Consequently, elevations of ALT activity following single episodes of hepato-cellular insult / damage will be transient. Persistent ALT elevations imply ongoing Hepato-cellular damage or insult.

Serum alkaline phosphatase (ALP) is a membrane-bound enzyme produced by the bile duct hepatocytes. An increased serum ALP level occurs whenever there is cholestasis. Unlike ALT, ALP is used as an indicator of either intra-hepatic or extra hepatic biliary obstruction and not hepato-cellular insult or damage. ALP is not a liver-specific enzyme. Measurable ALP is also found in bone, placenta, intestine, and kidney. Both exogenous and endogenous steroids can induce the production of a liver produced ALP isoenzyme in the dog but not in the cat. In addition certain drugs such as Phenobarbital and potassium bromide can directly induce liver ALP production. "Healthy" aging dogs may exhibit an elevated serum alkaline phosphate levels associated with "normal" fatty infiltration and/or nodular hepatopathies of the liver parenchyma. In general, 2 to 3 times elevations of ALP levels in older "normal" dogs are regarded as non-specific and may be considered a "normal" aging change. However 2 to 3 X elevations of ALP levels could also be the result of liver disease, bone disease, drug induced, or early Cushing's disease. At what point should a mild (2- 4X) elevation in ALP; in a "healthy" patient be investigated?

ALP elevations secondary to cholestasis may occur with or without concurrent elevations of ALT. Most acute conditions causing hepato-cellular injury or damage also cause intra-hepatic cholestasis resulting in elevated ALP levels. In contrast, many chronic hepatic disorders or chronic active hepatic diseases are characterized by periportal fibrosis with resultant cholestasis (elevated ALP levels), with only mild elevations in ALT levels; indicative of minimal active hepato-cellular injury. This is especially significant in cats.

Obviously interpretation of serum ALP levels in cats is different than dogs. The ALP enzyme levels in cat livers are much lower than in dogs. In addition, the circulating half-life of ALP in cats is significantly shorter than that of dogs. As a consequence, any elevation in ALP level in cats is considered a significant indication of cholestasis as compared to older dogs.

GGT, serum gamma glutamyl transferase is another membrane bound enzyme associated with the hepatic bile duct cells. Both ALP and GGT are indicators of cholestasis. Measuring both GGT and ALP levels is probably most useful in cats where elevations in ALP are often more subtle. Elevations of both enzymes reinforces the fact that cholestasis is present. In cats, a relatively greater increase in ALP than GGT is suggestive of hepatic lipidosis.

Indirect liver function tests that may be included on a routine chemistry profile include albumin, BUN, glucose, and cholesterol. Since the majority of the plasma proteins, especially albumin, are produced in the liver, severe end stage liver disease may be a cause of hypo-proteinuria, especially hypoalbuminemia, due to decreased liver production. Due to the relatively long half-lives of plasma proteins (7-10 days), such alternations are usually seen only in chronic liver disease. Chronic liver disease may result in a decreased BUN levels. Because lipid metabolism, cholesterol production, is an important liver function, decrease serum cholesterol is associated with hepatic insufficiency (end stage liver disease). Chronic severe liver disease can cause hypoglycemia. This is a reflection of decreased glycogen storage capacity and reduced functional hepatic mass. The presence of hypoglycemia in cases of obvious liver disease is therefore a poor prognostic sign. Postprandial hyperglycemia in liver disease cases is also due to reduced functional glucose storage mass. Pre / post prandial Bile acids are the definitive liver function test!

Sensory decline

Decreases in hearing and vision are very common age-related problems that increase in frequency with aging. Changes in vision and hearing are referred to as sensory dysfunctions and often result in changes in behavior patterns. Unfortunately these sensory dysfunctions behaviors may not be recognized as such leading to a miss-diagnosis of senility, dementia or Cognitive Dysfunction Syndrome as the symptoms can be very similar.

Hearing loss

The loss of hearing in older dogs and some cats is well recognized. In one study, 48% of dogs over 12 years of age had significant hear deficits including deafness. By 16 years of age, 97% had significant hearing deficits including total deafness. Hearing loss associated with decreased sound wave conduction from the external ear to the cochlea (conduction deafness) can be helped with amplification. Dogs with fibrotic or ruptured tympanums fit into this category. Neurogenic deafness (sensorineural), i.e., specific loss of nerve function, is the most common cause of deafness in older dogs. Amplification will not help this type of deafness. However, the use of a vibrating collar will help get the pets attention. Early in the course of hearing decline, a high-frequency dog whistle is a temporary solution until the ultra-high frequency sound receptors are is also lost.

Visual decline

In a recent study, 41% of dogs over twelve years of age had some degree of visual impairment. By age sixteen, 68% of dogs were affected. The normal aging changes in the lens called nucleus or lenticular sclerosis should be always differentiated from opacities of the lens/capsule called cataracts. Lenticular sclerosis is never a cause for visual impairment. All cataracts should be staged, the animal visual obstacle tested, and the retinas examined to evaluate whether cataract extraction would be beneficial.

Cardiovascular decline

Functional reserve is reduced with age due to myocardial fibrosis and free wall thickening. These changes reduce efficiency, ventricular filling and cardiac output. Regional and organ blood flow also decreases. To compensate for a decreased cardiac output, older patients primarily increase the stroke volume mainly through increased preload and increased atrial kick.

Chronic valvular disease resulting in varying degrees of valvular incompetence is the most common (75% of all cardiac disease) heart condition of older dogs. Older toy and small breeds are over represented. The cardiac valves, especially the mitral valve undergo "normal" aging changes that are referred to as valular fibrosis, valular endocardiosis, or myxomatous valular changes. These valular changes can result in the loss of normal integrity and weakening of normal valular structures. The resulting degree of valular incompetence / insufficiency resulting in the regurgitation heart murmur associated with the corresponding valve(s). The typical murmur is a low intensity, left sided systolic murmur hear loudest over the left heart apex. The use of a pediatric stethoscope on small breed dogs and cats will increase the chances of early murmur detection. The diagnosis can be confirmed with echocardiography and/or color Doppler echocardiography). Trending with thoracic radiographs is beneficial in staging the progressive left atrial and ventricular changes plus assessing the degree of venous congestion and eventual pulmonary edema.

Two cardiac bio-markers are available for small animals; cardiac Tnl and NT-proBNP. Cardiac Tnl is an intercellular myofibril protein associated with some degree of myocardial injury such as myocarditis, HCM, and cardiac hemangiosarcoma. In contrast, cardiac amino-terminal probrain natriuretic peptide (NT-proBNP) has been proposed as a useful biomarker for heart disease in dogs and cats. NT pro-BNP is correlated with the degree of cardiac muscle stretching. NT pro-BNP levels elevate in dogs and cats with common heart valvular diseases and heartworm disease and therefore may correlate with the severity of chronic heart diseases. The indisputable application of this test is to help differentiate between primary cardiac versus respiratory disease. It is also be useful in trending cases with an audible murmur; exercise intolerance; shortness of breath, coughing, and suspected congestive heart failure.

Pulmonary decline

Mechanically the patient loses thoracic compliance, develops progressive atrophy of the diaphragm and intercostals muscles, and loses alveolar elasticity. The result is a decrease in arterial oxygen concentration. While difficult to quantify, it is very important in general anesthesia.

Declining immunity

Immunosenescence refers to the gradual deterioration of the immune system brought on by natural age advancement. Decreases in both cellular and humoral immunity are closely associated with the aging process, and should be considered a major contributory factor to the increased frequency of morbidity and mortality among older pets. In addition to the increasing prevalence of tumor growth and infection rates, the development of short and long-term loss of immune memory, especially by vaccination, could be considered problematic. What should the vaccination recommendations be for the senior pets? To aid in supporting the patient' s immune function, dietary vitamin E helps with T cell activation, dietary lutein helps with B cell activation including vaccine recognition and beta carotene increases circulating antibodies and optimizes vaccine antigen recognition. These supplements are commonly incorporated into premium "senior" diets.

Our goals should be to optimize the quality of life for the older pet, using preventive health care strategies combined with state-of-the-art diagnostics and therapeutics. Historically, veterinarians have only reacted to those diseases and age-related problems in elderly pets. We need to refocus our efforts on a more proactive approach to older patients, and thus, not waiting until overt disease is present. The Senior Care program should emphasize slowing the aging process, implementing steps for prevention and early detection of age-related diseases, plus vital client education programs.