JOSEPH A. DYE AND ROBERT W. DOUGHERTY.
KETOSIS in dairy cattle is not a specific disease but a metabolic disorder. It is an imbalance between the nutritive intake and the nutritive requirements of the animal.
The lack of balance is indicated by several associated disturbances: Low blood glucose levels (hypoglycemia); depletion of liver glycogen (glucose stores); mobilization of body proteins, as amino acids, to the liver for new production of glucose (gluconeogenesis); mobilization of storage fat; fatty infiltration of the liver; increased production of ketone bodies; increased ketone bodies in the blood and urine; loss of body weight (emaciation); lower milk production; and dehydration.
One may compare ketosis to a bank account. At the beginning one may assume that the account is in balance and the reserve is big enough to draw on in an emergency. If the income falls below the expenditures and if the emergency is prolonged or is severe, however, the condition may become serious.
THAT GENERAL REASONING may be applied to the high-producing dairy cow, which is metabolically a delicately balanced milk-producing "machine."
At the time of calving and onset of lactation, the animal's nutritive and metabolic requirements are increased about 100 percent partly because of the loss of sugar, protein, and fat in the milk and partly because of the increased metabolic work associated with the production and secretion of milk.
For every 20 pounds of milk produced, approximately 1 pound of glucose, 0.8 pound of fat, and 0.7 pound of protein are withdrawn from the animal. Those withdrawals are from the animal's available resources. If the dietary intake is adequate, the animal remains normal. If the diet is too poor to maintain approximately normal levels of blood glucose and liver glycogen, an imbalance in metabolism develops.
This upset is indicated by the existing anorexia (loss of appetite), hypoglycemia, and depletion of liver glycogen. In response to these disturbances, compensatory metabolic adjustments are initiated and tend to correct the imbalance.
The adjustments are triggered primarily by the hypoglycemia via specific physiological mechanisms. Some of the mechanisms are nervous in character. Others are linked to hormone actions. The hormones include primarily ACTH and possibly growth hormone of the anterior pituitary gland and hormones produced by the adrenal cortex such as cortisone and 17-hydroxycorticosterone.
The important physiological effects are an increased mobilization of depot fat and fatty infiltration of the liver and an increased mobilization of amino acids from body protein to the liver, in which some are converted to glucose and glycogen. Fatty infiltration of the liver tends to produce a temporary increase in ketogenesis (the production of ketone bodies). Glucose or glycogen tends to prevent it.
Small doses of these hormones of the adrenal cortex may cause a temporary increase in ketogenesis, but as the glucose production by the liver is sufficiently increased, ketogenesis is checked. Glucose acts to prevent ketogenesis from fatty acids by the liver by maintaining a small supply of "oxalacetate," which has to combine with fatty acid fragments if they are to be oxidized. If fatty-acid oxidation in the liver is blocked by a deficiency of oxalacetate, the metabolism of fatty acids is incomplete and ketogenesis may occur.
A SECOND FACTOR that may lead to the development of ketosis in dairy cattle is the unique nature of rumen digestion. The microbial fermentation of carbohydrates in the rumen leads to the production of large amounts of the lower fatty acids. A high percentage of them is ketogenic, and about 20 percent propionic acid can be converted to glucose by the animal body.
The true dietary intake of carbohydrate, compared to that of carnivores, therefore is relatively small, and the intake of potential formers of ketone bodies is large. If, however, the blood glucose and liver glycogen levels can be maintained, both glucose and fatty acids are oxidized and ketosis does not occur.
On the contrary, when the blood glucose is low, the carbohydrate stores in the liver tend to become depleted in an attempt to maintain the level of blood glucose and, in turn, the carbohydrate requirements of other tissues. Ketogenesis and ketosis tend to develop under those conditions. An abnormal amount of ketone bodies in the blood, body fluids, and tissues characterizes ketosis.
The liver is the principal organ in which ketone bodies are produced. They are normal intermediary metabolites, associated chiefly with the metabolism of fatty acids under conditions of relative deficiency of the carbohydrates. The intensity of the ketosis is directly related to the level of the deficiency.
Ketone bodies cannot be metabolized further by the liver but are passed into the blood and to the other tissues, where they can be oxidized. Ketosis develops only when the rate of ketone body production (ketogenesis) exceeds that at which they are utilized. There is no inability of the tissues, other than the liver, to oxidize either glucose or ketone bodies under those conditions. Although the concentration of ketone bodies in the blood is high, only a fraction of those produced is excreted by the kidneys, the mammary glands, and expired air.
KETOGENESIS and ketosis are not due to an initial or absolute deficiency in the hormonal secretory capacity of the anterior pituitary or adrenal cortex in fact, such deficiencies would make ketogenesis nearly impossible.
Because of the increased metabolic requirements of the animal under the stress of high milk production, starvation, disease, and other single or multiple conditions, the anterior pituitary and adrenal cortex and various available body resources are mobilized to meet the immediate metabolic requirements. The resources include the mobilization of depot fat and muscle proteins as amino acids. The former is associated with fatty infiltration of the liver. The latter leads to an increased conversion of amino acids to glucose in the liver and an increased urinary nitrogen excretion. Both lead to emaciation of the animal.
Under those conditions, a relative anterior pituitary or an adrenal cortex secretory deficiency, or both, usually develops.
The hormonal mechanism for stimulation of the adrenal cortex by a specific hormone (ACTH) from the anterior pituitary may induce an enlargement and increase in number of cells of the adrenal cortex. Within wide limits, this is a physiological process; if it were followed by cellular degeneration or complete exhaustion, however, the results might be fatal. That occurs rarely.
VARIOUS CLINICAL CLASSIFICATIONS of bovine ketosis have been used.
Lactation ketosis includes cases that suffer from a simple imbalance between the nutritive intake and the nutritive requirements to maintain the increased demands of the lactating animal. This type occurs most frequently 14 to 28 days after parturition, but may occur as early as the seventh day and as late as 40 to 70 days after calving. The cases often are classified as uncomplicated, primary, and digestive ketosis, which occur in most countries where ketosis is prevalent. The terms "small-farm acetonemia" (in which the nutrition may be inadequate) and "estate acetonemia" (in herds apparently in good nutrition, but in which the acetonemia is frequently severe) are used in the British Isles.
Complicated or secondary ketosis may occur in varying intensities in lactating or nonlactating cattle even in steers and include cases in which the metabolic disturbance is precipitated or aggravated by infections, exposure, foreign bodies (hardware) in the rumen or reticulum (traumatic gastritis), peritonitis, mastitis, cystic ovaries, vaginitis, displacement of the abomasum, indigestion, and starvation. The treatment and correction of the complicating factor or factors in such cases is imperative if the animal is to recover.
DIGESTIVE KETOSIS INCLUDES the cases we listed that do not develop the so-called nervous symptoms.
In nervous ketosis the animals usually are reported to be excited and show signs of neuromuscular incoordination. They keep looking around and are disturbed if someone enters the stall. The condition is occasionally described as a semiconscious state and one indicating a depression of the cortical nerve centers of the brain. The manner of walking of the animal is often staggering, swaying, and more or less paretic and listless. Other symptoms are frequent licking of the stanchion walls, sucking, biting, salivating, and hyperesthesia of the skin. Those disturbances probably are due to a progressive depression of the higher nerve centers in the brain, which in turn progressively releases the sub-cortical centers in the brain stem.
Nervous symptoms of ketosis have been produced in fasting pregnant ewes by relatively severe hypoglycemias and in normal ewes and cows by the intravenous administration of isopropanol (an alcohol). Isopropanol is present in appreciable amounts in rumen liquor, blood, and milk of ketotic ruminants. The isopropanol concentration is greatest in the rumen, and is believed to be formed from acetone by the ruminal micro-organisms. The combined effects of hypoglycemia and isopropanol may act in an additive or synergistic manner to produce the effects. Similar effects occur in various species of animals under incomplete anesthesia and in intoxicated persons.
KETOSIS IN CATTLE occurs in practically every country in which dairying is practiced. Only a few cases occur in some regions, but in others its incidence may be 15 percent or more.
It develops primarily in high-producing dairy cows and seldom in low-producing cows, steers, or bulls, except those suffering prolonged starvation and protracted diseases. In many areas the number of recognized cases of ketosis has increased greatly since 1940. The first described case of ketosis in cattle in the United States is reported to have been in 1929.
Ketosis may occur in dairy cattle of all ages, but is more prevalent during the years of greatest milk production after the second, third, and later lactation periods.
A million cases of ketosis occurred in 1950 among the 24,577,000 milking cows in the United States, an incidence of approximately 4 percent.
Mortality from ketosis in dairy cattle is low, ranging from 1 to 5 percent. Lactation ketosis is rarely fatal even if untreated not more than 1 or 2 percent. Reports for "estate ketosis" indicate a somewhat higher death rate.