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

"Old age" in not a disease but is the sum of the deleterious effects of time upon the cellular function, microanatomy and physiology of each body system. These biological aging changes manifest in progressive deteriorations in physical condition, organ function, mental function, and immune response, but not necessarily correlating with the patient's actual chronological age. Consequently, each internal organ system will age at a different rate; biological aging. Using the patient's age as a benchmark of his collective decline is appropriate. However, because each organ has a different rate of biological aging, any critical assessment of a patient's overall health status should be based on a comprehensive health screening of both mental and organ functions, when possible.

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. As the functional organ reserves are gradually lost, the long-term result is a physiological decline of the major organ systems leading to an altered response to stressors, infections and various drugs. At some stage in the progressive decline the "tipping point" is reached, all physiological reserves are exhausted resulting in overt changes in diagnostic screening tests, biochemical parameters, and/or the onset of clinical symptoms of age-related disease referred to as "benchmarks". 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 a specific patient is best managed. Assessment of the level of physiological decline in each organ system requires diagnostic evaluations. The 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. It is important to convey this pertinent information to owners and staff. Intimate knowledge of the early warning signs of the 10 most common life threatening diseases in the elderly pets, alerts the health care team 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.

Metabolism Changes

As animals age, their basal metabolic rate (BMR) decreases. The consequences of decreasing BMR include; increased production of free radicals; cold intolerance; and weight gain if there is not a corresponding decrease in caloric intake. With a decreased BMR, less metabolic heat is generated resulting in a progressive "cold intolerant" patient. Another consequence of a decreased BMR is slower cell turnover within the gastrointestinal tract increasing the patient's susceptible to GI erosion and ulceration.

Weight Changes

The pet's weight and weight changes are good indicators of overall health and health risks. The health risks of obesity have been clearly documented in the last decade. However any gradual changes in the overall body condition are not easily detected by the owner. Regular weight monitoring combined with body condition scoring allows the veterinarian to better assess minor or earlier changes especially in multi-doctor practices. Based on ideal weight, older patients can be placed in three classifications; pets within the normal weight range, animals that are too thin, and patients that are overweight or obese.

Decreases in activity and basal metabolic rates without a corresponding decrease in caloric intake produces the overweight pet. Several studies have shown that geriatric pets are often too thin. The issue is whether this lower body condition score is the result of some underlying disease state or just "normal' aging seen in dogs, cats and humans. Common age-related causes of insidious weight loss include metabolic diseases (chronic liver and renal disease), cardiac failure, cancer, and maldigestion conditions. Decreases in muscle mass is normal in older patients, and since muscle weighs more than fat, the muscle mass loss may reflect both the actual weight loss and decrease in body condition score. Decreases in muscle mass and partial age-related inappetance can be "normal" and common causes for a slow loss of weight.

Any decreased or picky appetite needs to be carefully investigated. Pathologic etiologies associated with a decreased appetite include dental disease, metabolic dysfunctions, a gastrointestinal disorder or cancer. In addition to the normal loss of olfactory neurons, normal loss of taste buds, masticatory muscle atrophy, a lack of sufficient saliva to easily swallowing dry food, and/or "senility" can also contribute to deceased appetite in the "healthy" older pet.

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. In the flip side, older patients are 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, usually less subcutaneous fat. Cold intolerance can also be a predominant sign of hypothyroidism. 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 especially the older patients. This change is related to a combination of inactivity 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 "prescription" diets. When faced with insufficient dietary essential amino acids, the patient must catabolize their own protein (essential AA's) 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

Impaired swallowing, 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 the 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. Uncovering chronic progressive renal disease is often difficult in the very 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.

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.

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 prescription lowered protein diets. There changing a patient to a lowered protein diet will "inaccurately" lower serum BUN levels although the renal function has not actually improved.

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. Trending is the concept of repeated monitoring / charting of a biological parameter in that is helpful in "predicting" the patient's future health status.

Proteinuria

Small plasma proteins are normally filtered through the glomerulus but are reabsorbed in the proximal convoluted tubules. Animals with normal renal function should have undetectable or trace amounts of protein in their urine. Since significant renal proteinuria (persistent microalbuminuria or overt proteinuria) can be the first laboratory finding with chronic progressive real disease. A complete urinalysis with specific gravity, dip Stix, and sediment examination is an essential part of a senior care program.

Physiologic proteinuria is usually mild, transient and caused by strenuous exercise or seizure activity. Causes of pathologic proteinuria include renal glomerular and/or tubular damage, hemorrhage, infection, inflammation, hemoglobin or myoglobin. Significant renal proteinuria (persistent microalbuminuria or overt proteinuria) can be the first laboratory finding with chronic progressive real disease and may actually occur before azotemia is evident. Since quantifying the amount of protein is an important diagnostic and prognostic tool, accuracy is critical. When evaluating a proteinuria case, the first step is to rule out extra urinary causes with a cystocentesis. In addition, a close sediment examination will aid in ruling out a UTI but often a culture is required. Quantify the protein using the UP/C ratio and/or ELISA MA test is an important step.

The "Bili-lab stix testing" measures primarily the presence of albumin in the urine. Since the lab stix "value" does not factor in urine concentration/dilution, the quantitative correlation is poor. The quantity of excreted protein is proportionate to the volume of urine produced. Therefore in high specific gravity urine samples a trace, 1+, and sometimes 2+ protein levels are observed in normal dogs. For this and other reasons, quantifying protein loss with a dip-stix is ill-advised. In the absence of inflammation or hemorrhage in the urine sediment, renal proteinuria can be best quantified by measuring the urine protein: creatinine ratio (UP/C).

While not as sensitive as the ELISA technology, but is very specific and considered the gold standard test in veterinary medicine. A urine protein: creatinine ratio of < 0.5 is considered normal. Values between 0.5 and 1.0 are considered borderline (probably significant) and values greater than 1.0 should be considered significantly abnormal IF the urine sediment is inactive. Microalbuminuria assessment using ELISA based technology is a very sensitive test but not as specific as the UP/C.

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 the "healthy" patient with only a mild (2-3 X) elevated ALP be worked up?

ALP elevations secondary to cholestasis may occur with or without concurrent elevations of ALT. Many acute conditions causing Hepato-cellular injury or damage with corresponding ALT release also cause Hepato-cellular swelling and intra-hepatic cholestasis resulting in elevated ALP levels. In contrast, many more chronic hepatic disorders or chronic active hepatic diseases are characterized by periportal fibrosis with resultant cholestasis (elevated ALP levels),but only mild to slightly elevated ALT levels indicative of little if any active Hepato-cellular injury especially in cats. 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.

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 either hypoglycemia or hyperglycemia. 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 / 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 decline, a high-frequency dog whistle is a temporary solution until the ultra-high frequency sound recognition is 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 heart condition of older dogs. The cardiac valves undergo "normal" aging changes that are referred to as either valular fibrosis or valular endocardiosis. These valular changes can result in some degree of valular incompetence (regurgitation) resulting in a heart murmur associated with the corresponding valve(s). Heart murmurs are common occurrences in older small breed dogs. Using a pediatric stethoscope on small breed dogs and cats will increase the chances of early murmur detection. Since the intensity of the murmur does not ALWAYS correlate with the regurgitation volume; the degree of cardiac compensation; or degree of cardiac insufficiency, all murmurs should be "trended" with imaging (radiographs and/or echocardiography).

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.

Central Nervous System Decline

Older animals undergo somewhat predictable personality changes with aging. Older pets need increasing amounts of attention and are exceedingly more jealous of new housemates and visitors. They are more irritable and less tolerant with once-endured actions of housemates, owners and visitors. Elderly pets are less mentally alert plus they sleep a larger percentage of time although the actual sleep patterns may be significantly altered. Most animals exhibit varying degrees of cognitive decline with age. However significant declines in the cognitive abilities of memory, learning, perception, and/or awareness are hallmarks of Cognitive Dysfunction Syndrome. For some patients, this represents a significant quality of life issues with usually unacceptable behaviors.

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. The supplements are commonly incorporated into "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.