Ketoacidosis is a metabolic imbalance that is most commonly seen as a sequel to unmanaged or poorly regulated diabetes mellitus. It is caused by the breakdown of fat and protein in a compensatory effort for the need of more metabolic energy. The excessive breakdown of these stored reserves creates a toxic by-product in the form of ketones. As ketones build up in the blood stream, pH and electrolyte imbalances proceed. This condition is a potentially life-threatening emergency that requires immediate medical attention.
Diabetes mellitus is a common endocrine disease in geriatric felines. It is caused by a dysfunction in the beta cells of the exocrine pancreas resulting in an absolute or relative deficiency of insulin. Insulin has been called the cells' gatekeeper. It attaches to the surface of cells and permits glucose, the cells' primary energy source, to enter from the blood. A lack of insulin results in a build up of glucose in the blood, physiologically causing a state of cellular starvation. In response to this condition the body begins to increase the mobilization of protein and fat storage. Fatty acids are released from adipose tissue, which are then oxidized by the liver. Normally, these fatty acids are formed into triglycerides. However, without insulin, these fatty acids are converted into ketone bodies, which cannot be utilized by the body. Together with the increased production and decreased utilization an abnormally high concentration of ketone bodies develop. These fixed acids are buffered by bicarbonate; however, the excessive amounts overwhelm and deplete the bicarbonate leading to an increase in arterial hydrogen ion concentration and a decrease in serum bicarbonate. This increase in hydrogen ions lowers the body's pH, leading to a metabolic acidosis.
The normal pH for a feline is 7.4 and is necessary for the normal function of many enzyme systems. When pH drops below this value the cat is referred to as being acidotic. Normally, the cat can compensate for small drops in pH by increasing the ventilation rate to decrease carbon dioxide concentration and increase hydrogen ion excretion and bicarbonate retention by the kidneys. However, the excess of organic acids produced in diabetic ketoacidosis overwhelms these responses, requiring medical intervention.
Ketoacidosis can often be identified by a sweet smelling scent to the cat's breath. However, it is confirmed by the detection of ketone bodies in the urine, termed ketouria. Ketouria is caused by the increasing serum concentration of ketones in unmanaged diabetes that eventually leads to a spillage of the metabolite into the urine that can be detected with a urine reagent dip-strip. A positive result on a reagent strip is indicative of disease. However, a negative ketone strip does not definitively rule out ketosis because the nitroprusside reagent only detects the ketone bodies acetoacetate and acetone. It is not as sensitive for beta-hydroxybutyrate, the most prevalent ketone body. Therefore, in the face of a negative reagent strip, ketoacidosis can be diagnosed with other supportive evidence including an increased anion gap, decreased bicarbonate, decreased TCO2, venous or arterial blood gas if available, clinical signs, and history.
Patients suffering from diabetic ketocidosis most commonly present with dehydration, weakness, depression, vomiting, and an increased respiratory rate. Treatment must be initialized immediately to correct this rapidly progressive and deteriorating disorder, using fluid, insulin, and possibly bicarbonate therapy. The increase in both glucose and ketones within the urine creates an osmotic diuresis. Free water and electrolytes are lost in the urine causing a severe and perpetuating state of dehydration. Intravenous 0.9% saline is the fluid of choice for most cats since sodium levels are often significantly depleted. An initial intravenous rate of 60-100 mL/kg/day is recommended, however adjustments are made depending on hydration, ongoing losses, and shock status. Potassium supplements are often added to the fluid therapy, due to most cats being in a deficient state from urinary and vomiting loss and to prevent life-threateningly low levels from the increase in fluid volume and co-administration of insulin. Potassium and sodium levels should be carefully monitored both before and during fluid therapy and supplementation to ensure levels stay within an appropriate range.
Insulin therapy is instituted to allow for a gradual decline in blood glucose and ketones over six to ten hours. Regular small doses of crystalline insulin are given hourly and carefully monitored and adjusted depending on frequent glucose monitoring. The use of bicarbonate therapy is controversial since the acidosis is usually corrected by the metabolism of ketone bodies with the administration of insulin. Therefore bicarbonate supplementation is only used when metabolic acidosis is severe, with pH of 7.10-7.15 or lower. It is important to note that diabetes predisposes a cat for concurrent illness such as bacterial infections, pancreatitis, congestive heart failure and renal failure. Therefore therapy may vary from patient to patient in regards to antibiotic usage and fluid administration. Generally one to three days of hospitalization is required to stabilize a cat and correct its negative energy state. Once the cat is stable, eating and drinking on its own, and no longer receiving intravenous fluid support, the cat may be switched to a longer acting insulin for long-term regulation of blood glucose concentration.
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The Downs Veterinary Practice.
December 8th, 2003