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Ageing has been defined as a progressive reduction in the ability of an organism to meet the demands of the environment.

It results to loss of organ reserve, regenerative powers of organ function, and adaptability Mosier (1989). In old animals number of disease processes occur simultaneously so it becomes very difficult to determine true mechanism of death. True ageing changes, such as collagen cross linkages, increasing tissue fragility, loss of flexibility, loss of muscle and nerve cells, decreasing ability to survive stress, thickening of lens and wrinkling of the skin are progressive and irreversible. Ageing affects all the systems of the body, starting from eye, the incidence of loss of vision increases with age and most commonly seen at 12 or 13 years because of age related cataract (Houpt and Beaver 1981). A study was carried out in which 2000 dogs were examined with ophthalmoscope to determine presence of cataract. It was concluded that all dogs over 13.5 years were affected by some degree of lens opacity (Williams et al 2004). Eye undergoes many changes with age but cloudy appearance of the eye is one of the most common age related changes (Fischer 1989).The lens epithelium continuously produces additional lens tissue which does not get shed and cause central portion of the lens or nucleus hard. This is termed as nuclear sclerosis.

Nuclear sclerosis incidence increases with age and the lens cortex tends to become denatured and undergoes degeneration. It concurrently occur with age related cataract. Nuclear sclerosis if present alone may not lead to vision loss in an animal but when accompanied by age related cataract it leads to functional loss of vision( Fischer 1989). As age progresses there is thickening of the epithelium in the cornea of the dog, whether this is associated with real decrease in tear output or not (Kwiteo and Weinstock 1985). Increase incidence of loss of rods and cones has been seen in elderly dogs due to which disorganization of the remaining layers is

noticed. Also there were pigmentary changes with focal degeneration in the aged eye. Lipofuschin accumulation was seen in cells of retina (Mosier 1989).

Not only eye is effected with age it has been seen that hearing loss precedes the vision loss but is not appreciated until vision loss is combined with it (Fischer 1989). Cats of all ages and older dogs develop idiopathic vestibular disease (Sorjonen 1989).The hearing loss in geriatric animals primarily occurs from degeneration of peripheral acoustic structures and does not invole the CNS ( Sorjonen 1989). With increase in age there are atrophic changes of the mucosa, change in hydration of the tissue, and alterations in the vascular and nerve supple (Sorjonen 1989).

Cardiovascular system is the major body system and includes many important functions of the body but like other organs so as cardiovascular system is affected by senescence. As a dog's heart ages, it loses some efficiency and cannot pump as much blood in a given amount of time. The valves of the heart lose some of their elasticity and also contribute to a decreased pumping efficiency. The most common valve involved is the mitral valve, especially in small breeds. Diagnostic tests such as radiographs (x-rays), an electrocardiogram (EKG), and an echocardiogram can be used to diagnose heart disease Geriatric patients have decreased cardiac reserve compared to young patients and may have difficulty compensating for cardiovascular changes that occur during anaesthesia ( Paddleford 1989). Geriatric patients have decreased baroreceptor activity, blood volume, cardiac output, blood pressure, circulation time, and vagotonia ( Dodman et al 1984).

There are many disorders which affect functioning of heart but that mitral valve insufficiency is the most common heart disease in dogs accounting for 70 80 percent of the

cardiac disorders. Out of this 75 % disease incidence was seen in geriatric patients more than ten years of age, and was most commonly reported in males of small breeds (Eliz et al 2010). A study was carried out to evaluate healthy geriatric dogs for the presence of systemic hypertension. Thirty-three geriatric dogs (i.e., dogs exceeding the geriatric age and 22 control dogs (i.e., dogs less than six years of age) were evaluated by measuring blood pressure with an oscillometric monitor. Diastolic and mean blood pressure measurements were significantly lower in the geriatric group as compared to the control group (Meurs et al 2000). Normal functions of the heart is affected by many disorders in the elderly animal but cardiopulmonary disease is common in the geriatric animal and lead to lethargy, cough, dyspnea or syncope. Chronic valvular heart disease and various forms of chronic obstructive pulmonary disease are the most common geriatric cardiopulmonary disorders ( Bonagura 1981). Also it has been seen that chronic valvular degeneration and subsequent mitral valvular insufficiency is the most frequent cause of congestive heart failure in dogs. It is more common in male small breed and incidence increases with age ( Miller et al 1989). A study was conducted where major cardiovascular and metabolic parameters during and after physical exercise by treadmill-running in 510 year old Beagles was investigated. He concluded significant differences in the baseline values at rest in the younger dogs as compared with the older one. He found lower values of haematocrit, red blood cell count and haemoglobin concentration ,venous oxygen tension, lower oxygen saturation in venous blood as well as a significant lower plasma glucose level in the older animals during the recovery period. Also he found lower heart rate during and immediately after exercise, as well as body temperature after exercise, was significantly lower in the older animals (Strasser et al 1997).

Although the liver has an incredible and unique way of regenerating itself when injured, the liver does age just like all other organs in the body. Its ability to detoxify the blood and produce numerous enzymes and proteins gradually decreases with age. Sometimes, the liver enzymes measured in a chemistry panel may be abnormally elevated in an apparently normal animal. On the other hand reduction in liver functions is present even when standard biochemical function test are normal ( Green 1982).Altered hepatic functions in geriatric patients may lead to hypoproteinemia, delayed clotting function, and greater susceptibility to hypoglycemia (Paddleford 1989). It was observed that a 12-year old castrated male miniature schnauzer presented with a history of abdominal distension. Serum biochemical analysis and abdominal ultrasonography indicated hepatic disease. A wedge biopsy provided a diagnosis of chronic active hepatitis ( Hendrix 2004) C. Stockhaus et al 2002 evaluated liver cytology in 28 healthy dogs 114 years of age with normal liver structure and function. Smears were stained with May-Grnwald-Giemsa. Hepatocytes had distinct cell borders, and cells did not overlap. Cells with two nuclei and cells with intranuclear crystalloid structures were observed regularly. Cytoplasm contained small numbers of vacuoles characteristic of glycogen and lipid and small amounts of pigment consistent with ceroid or bile. Nuclei were uniform. Mean parenchymal cell sizes were significantly greater in older dogs, but no age-related differences were observed in nuclear size. Older dogs also had a significantly increased number of nuclei per cell. There were more neutrophils in young and old dogs than in middle-aged dogs. Also A 9-year old female Yorkshire terrier presented for vomiting and diarrhea. Blood chemistry tests revealed hepatic dysfunction, cholestasis, and inflammation. Liver ultrasonography and liver biopsy were consistent with cholangiohepatitis. Fine-needle aspiration of the gallbladder revealed the presence of bacteria

later identified as Clostridium spp. The cholangiohepatitis was successfully treated ( Ramery et al 2012)

As animals age, the risk of kidney disease increases. This may be due to changes in the kidney itelf or result from the dysfunction of other organs such as the heart, which if not functioning properly, will decrease blood flow to the kidneys. Kidney function can be measured through chemistry tests on the blood and a urinalysis. These tests can identify a kidney problem well before there are any physical signs of disease. The most frequent sign of kidney disease first noted by an owner would be an increase in water consumption and urination, but this generally does not occur until about 70% of the kidney function is lost. A gradual decline in kidney function is a normal part of growing old. There is decrease in weight of kidneys and it is difficult to differentiate between cortical and medullary areas of kidney. There is decrease in number of nephrons which is the functional unit of kidney. With increase in age there is decrease glomerular filteration rate as a result of interstitial pressure, decreased blood pressure, decreased blood volume , and altered permeability of the glomerular membrane (Mosier 1989). A study was carried out in seventeen dogs with chronic renal failure (CRF).A non regenerative,

normochromic, normocytic anemia was seen in 12 out of 17 dogs (70.6%). There was a direct correlation between the degree of anemia and the extent of CRF as assessed by serum creatinine concentrations (King et al 2008). A study mentioned that chronic renal failure (CRF) is the most common form of renal disease in dogs and cats. Although CRF occurs in dogs and cats of all ages, it is commonly considered a disease of older animals, and the incidence increases with age. Nephrolithiasis is uncommon in dogs and cats, accounting for less than 3% of all urinary calculi (Rubin 1997).Chronic renal disease leading to Chronic renal failure is a major cause of

morbidity and mortality in dogs and cats. The prevalence of chronic renal disease increases with

age, and the underlying lesions are often irreversible as well as progressive. An annual health examination that includes a complete blood count, serum biochemistry profile and urinalysis is one of the best ways to detect declining renal functions. (Grauer 2005) Kidneys of geriatric animals are smaller in weight and size, have decreased glomerular numbers, tubular size and weight, and have increased mesangium and fibrosis which leads to decreased renal blood flow, glomerular filteration, urinary concentration ability and decreased ability to maintain sodium, water and acid base homeostasis( Samiy 1983). A study on 35 geriatric, uninephrectomized, spayed Beagle bitches under controlled, but varied dietary condition for 4 years was done to measure renal cortical and renal medullary echogenicity relative to hepatic and splenic echogenicity which concluded that regardless of the diet fed, 60-75% of these aged dogs had renal cortical echogenicity less than that of either the liver or spleen across time; 25-35% of these dogs had renal cortical echogenicity equal to that of the liver, therefore, in either mature or aged dogs imaged with 4.0 to 5.0 MHz equipment, the renal cortical echogenicity should be considered normal if it is less than or equal to that of the liver and less than that of the spleen (Churchill et al 1999) Urinary incontinence is involuntary or uncontrollable leaking of urine from the bladder. In older dogs, especially spayed females, small quantities of urine may leak from the urethra while the dog is resting or sleeping. The average age of dogs with acquired urinary incontinence is between 5.3 and 8.3 years which indicated that urinary incontinence is primarily a disease of middle-aged or older animals( DiBartola and Adams 1983).Calcium oxalate (CaOx) uroliths are one of the most common urolith types in dogs, cats, and humans. Many factors predispose animals to CaOx uroliths, including breed, old age, obesity, male sex, being neutered, and certain diseases. Management and prevention should be focused as there are no effective strategies for medical dissolution of these uroliths(

Gisselman et al 2009). A case control study was done to test the hypothesis that breed, age, sex, body condition, and environment are risk factors for development of calcium oxalate uroliths in dogs. He had 1,074 dogs that formed calcium oxalate uroliths and 1,724 control dogs that did not have uroliths. He concluded that middle-aged (8 to 12 year-old) castrated male dogs had increased risk for formation of calcium oxalate uroliths. Urolith formation was also associated with increasing age. Dogs of certain breeds, including Miniature and Standard Schnauzer, Lhasa Apso, Yorkshire Terrier, Bichon Frise, Shih Tzu, and Miniature and Toy Poodle, had increased risk for developing calcium oxalate uroliths. Overweight dogs also had increased risk (Lekcharoensuk et al 2000).

Arthritis is a common occurrence in older dogs, especially large breed dogs and breeds which have a tendency to have intervertebral (IV) disc disease. Arthritis in dogs may only cause a slight stiffness, or it can become debilitating. As with muscles in people (if you do not use them, you lose them), older dogs who are inactive will lose muscle mass and tone. This may make it more difficult for them to move, so they move less, etc., and a vicious cycle starts. The number and size of muscle cells are reduced with age. Decreasing function may be due to increasing fibrosis, muscle fiber atrophy, and reduced sensitivity to adenosine triphosphate (Mosier 1989). Senior dogs with orthopedic injuries and diseases often require a treatment plan that differs from that of younger patients. Injured bone and soft tissues tend to heal more slowly in the geriatric patient. The older animal is likely to have a less competent immune system and may have compromised metabolic and endocrine function (Beagle 2005).

A study was conducted in which lateral radiographs of 310 female beagle dogs from a closed colony showed development of spondylosis deformans that was age-dependent and

located principally at discs numbers 5, 15, and 20 to 23.It was concluded that Spondylosis deformans is a generalized disease of ageing resulting in formation of bony osteophytes around degenerating intervertebral discs throughout the vertebral column (Morgan 1989).

Radiologic, pathologic, and ancillary methods were used to determine the occurrence of degenerative joint disease involving multiple joints of adult dogs. A similar pattern of polyarticular osteoarthritis was revealed from necropsy reports from medical case records of 100 adult and elderly dogs (Olsewski et al 1983).A study was conducted in which shoulder joints of 149 Beagles over 8 years old at the time of death (mean age, 13.8 years +/- 3.21), were examined radiographically throughout their life-times for the frequency of degenerative joint disease (DJD). Serial clinical radiographic studies indicated that normal shoulder joint development during the first year of life was followed by the appearance of subchondral bone sclerosis and bony remodeling of normal joint contour, and by the formation of periarticular osteophytes and nthesiophytes. All changes were progressive with age and typical for DJD in dogs (Morgan 1987).

Some glands tend to produce less hormones as they age, and other glands may produce more such as in Cushing's Disease. Hormonal problems are a common disorder in many older dogs, and the propensity to develop a problem is sometimes linked to breed. The Golden Retriever, for example, has a much greater risk of developing hypothyroidism. Hypothyroidism is the most commonly diagnosed endocrinopathy of dogs (Meeking 2005). Also Canine hyperadrenocorticism is a common disorder in the dog and probably the most common endocrinopathy encountered in geriatric patients. The majority of cases (90%) occur as the result

of pituitary hypersecretion of ACTH, which results in bilateral adrenal hyperplasia and an overproduction of cortisol ( Bruyette et al 1995)

Simpson and McCown observed a a 12-year-old spayed female Alaskan Malamute with long-term history of panting, polydypsia and polyuria, weight loss, hind limb weakness, and a decrease in appetite. He diagnosed systolic blood pressure of 250 mm Hg. Palpation of the ventral cervical region revealed a fixed asymmetric mass in the area of the lobes of the thyroid gland histologic examination of which revealed a bilateral, multilobulated, and encapsulated thyroid gland adenocarcinoma. Hyperthyroidism was diagnosed on the basis of high serum thyroxine concentrations. A retrospective study on 180000 dogs was done. Survival analysis was performed for the outcome diagnosis of diabetes mellitus with age and sex. The mean age for the 860 diabetes mellitus dogs (72% females) was 8.6 years. Australian Terriers, Samoyeds, Swedish Elkhounds, and Swedish Lapphunds were found to have the highest incidence. The proportion of females with diabetes mellitus varied significantly among breeds. Swedish Elkhounds, Beagles, Norwegian Elkhounds, and Border Collies that developed diabetes mellitus were almost exclusively females ( Fall et al 2008).

When an unneutered male dog reaches 8 years of age, he has a greater than 80% chance of developing prostate disease, but it is rarely cancerous. In most cases, the prostate just enlarges. The prostate enlargement, however, can cause problems with urination or defecation. Older male dogs, especially those who are not neutered should have their prostate gland checked as part of the regular physical exam. The risk of prostate disease can be greatly reduced if the dog is neutered. Testicles show flaccid atrophy and/or tumor formation. Tumor prevalence may reach

60% in old dogs. Ovaries show a gradual increase in weight upto 13 years, then atrophy (Mosier 1989). A study on 198 dogs aged between 37weeks and 7.75 years. When juvenile dogs were studied, a significant proportion show low testicular weight, incomplete spermatogenesis and immature prostate development after 13-week observation periods. 10% of dogs maintained for a 7-year observation period developed testicular neoplasms and a further 8% showed interstitial cell hyperplasia. Epithelial hyperplasia of the ductus epididymis and benign prostate enlargement were also normal features of the aged male Beagle ( James and Heywoodn 1979)

A 10-year-old, entire, male, mixed-breed dog presented for severe haematuria and stranguria. Ultrasound revealed a large intraluminal urinary bladder blood clot and a prostatic space-occupying lesion. Post-mortem examination revealed primary prostatic haemangiosarcoma infiltrating the urethra. Haemangiosarcoma should be considered as a rare cause of prostatic mass lesions, haematuria or lower urinary tract signs in dogs.( Della Santa et al 2008). Common canine prostatic disorders include benign prostatic hypertrophy (BPH), prostatitis, prostatic cysts and prostatic adenocarcinoma. BPH is a spontaneous and age-related disorder of intact male dogs, which occurs in more than 80% male dogs over 5 years of age, and which is associated with clinical signs of sanguinous prostatic fluid, constipation and dysuria. Two studies suggest that risk of prostatic adenocarcinoma is increased in neutered, compared to intact male dogs. Recent reports of prostatic intraepithelial neoplasia (PIN) in a high percentage of older male dogs, with and without prostatic adenocarcinoma, suggests that PIN may be a precursor to adenocarcinoma in the dog ( Johnston et al 2000) . A study was conducted in which the prostate, testes, and serum testosterone levels were evaluated in healthy Beagle dogs that were grouped by age to provide five groups of dogs that ranged from 3 to 14 years of age. All animals 6 years of age and older had histologic characteristics of complex benign prostatic hyperplasia. A mean

statistically significant increase in prostatic weight with increased age was noted. The epithelial component did not contribute to the increase noted, with the exception that the percentage of glandular lumen did increase with age, indicating progressive cystic dilatation of the glands. Stereologic analysis of the testes showed a decrease in the relative percentage of germ cells with increasing age ( Lowseth1 1990).

Incidence of pyometra in colony-raised beagle dogs over a 12 year period. Pyometra was observed in 25 female dogs of more than 4 years old, frequently at 8-11 years, with the average age of onset 9.36 +/- 0.38 years. The incidence of the disease was 15.2% of the female dogs (n = 165) more than 4 years old. Clinical findings useful in the diagnosis of this disease included an excretion of pus from the cervix, rapid increase in leukocyte count, and enlarged uterus as revealed by radiography. In conclusion, the results indicated that pyometra might be an age-related disease because it occurred particularly in aged dogs ( Fukuda 2001).The immune system was studied in 34 bitches affected by pyometra. The mean age of the animals was 8-12 years. Leucocytosis (neutrophilia and partial monocytosis) and lymphopenia were detected in 62 % and 35 % of the bitches, respectively. The increase in the number of leucocytes was higher in the severely affected bitches. Sera from bitches affected by pyometra also had higher levels of immunoglobulins, lysozyme and circulating immune complexes. It can be concluded that pyometra is associated with an inflammatory response, but also with a marked suppression of immune system activity (Faldyna et al 2001). An 8-year-old intact female West Highland White Terrier was examined for anorexia, vomiting, abdominal distension, and mild purulent vulvar discharge. Emphysematous pyometra was suspected and confirmed at surgery. Clostridium perfringens was isolated from the uterine lumen ( Hernandez 2003).

A seven-year-old entire female, mixed breed dog, presented with a 2 day history of abdominal distension, reduced appetite and general dullness. Abdominal palpation revealed a large mass. Radiography showed a large mass occupying the left mid-abdominal area and convoluted loops of tubular fluid opacity occupying the right mid-abdominal area. Ultrasonography revealed a large heterogeneous mass with an anechoic area and some hyperechoic foci, indicative of calcification, in the mid-abdominal area. Furthermore, hypoechoic areas were found in the middle and caudal abdominal area and were presumed to be the fluid-filled uterine horns.. A diagnosis of uterine leiomyosarcoma associated with pyometra was established by histopathology and immunohistochemistry ( Tsioli et al 2011)

As with people, older dogs may start to show gray hair; this most commonly occurs on the muzzle and around the eyes. The haircoat may become thinner and duller, haircoat loose its luster.The skin of the older dog may become thinner, and thus more subject to injury. Some older dogs develop multiple benign tumors of the skin, which are generally not removed unless easily traumatized. Cancerous tumors of the skin can also occur. Dry skin can be a problem for older dogs. It is common for older, large breed dogs to develop calluses on their elbows, reason for this is the tendency of older dogs to be less active and lay down more. Also there is thickening of the foot pads and changes in the nails of older dogs. They may tend to become brittle. With increase in age of the animal , skin becomes more pliable and histologic changes are more apparent in geriatric animal (Baker 1967).The epidermis shows atrophy in old age, often becoming only one to three - cells thick with diminished number of cells ( Mosier 1989) A study was conducted in which 3% prevalence of squamous cell carcinoma and 25 % of lipoma have been reported in old Beagles concluding that older dogs are more prone to have skin tumors (Mosier 1989).With increasing age , arrector pili muscles become more eosinophillic and fragmented, with

vacuolated areas in individual fibers (Mosier 1989).There is increased immunologic alterations with age ( Mosier 1989).Alopecia develops as result of decreased follicular activity and skin becomes dull and lusterless ( Mosier 1989)

The mammary gland may show evidence of fibrocystic disease or neoplasia. By 11 years 60% of intact females have nodules or tumors. Mammary tumors comprise 25% of all neoplasms of the bitch (Mosier 1989). A study was conducted in which 14401 histologically verified tumor cases were taken up and calculated incidence of mammary tumors along with the age and breed specific incidence of mammary tumors in female dogs of three different breeds. The highest relative risk ratio of mammary tumors was found in Boxers, Cocker Spaniels, English Springer Spaniels and Dachshunds. The mean age of histologically diagnosed mammary tumors was 7.9 years in Boxers and 7.8 years in Springer Spaniels, compared with 8.8 years in all other breeds (Moe 2001).Primary hepatic tumors are most common in dogs that are 10 years of age or older. Hepatocellular carcinoma is the most common primary hepatic tumors in dog. A case of synchronously occurring (double) tumours, i.e. primary hepatocellular carcinoma and aortic body chemodectoma in a 14-year-old mixed-breed male dog. The tumours were identified during necropsy, following euthanasia. In the last months of its life, the dog showed signs of weakness, anorexia, apathy, inactivity, and abdominal palpation elicited a painful reaction. The primary liver cancer emerged in the left lateral lobe without evidence of any distant metastases (Sterczer et al 2011).Older dogs are more prone to tumors of skin, 3% prevalence of squamous cell carcinoma and 25 % of lipoma have been reported in old Beagles concluding that older dogs are more prone to have skin tumors (Mosier 1989).Bladder tumors are the most common tumor of the urinary tract (Theilen 1979).They occur primarily in older dogs, and average age for

occurrence of this tumor was 9.1 and 9.4 years (Burnie 1983). Prostatic tumors is seen primarily in dogs older than 10 years of age (Hornbuckle 1978)

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