Merck Veterinary Manual

MERCK VETERINARY MANUAL - SUMMARY

Merck Veterinary Manual - Summary

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Circulatory System Red Blood Cells The only known hemoglobinopathy of animals is porphyria. Although described in several species, it is most important as a cause of photosensitivity in cattle (see Photosensitization: Introduction). In most species, the kidney is both the sensor organ and the major site of erythropoietin production, so chronic renal failure is associated with anemia. Erythropoietin acts on the marrow in concert with other humoral mediators to increase the number of stem cells entering RBC production, to shorten maturation time, and to cause early release of reticulocytes. Removal of aged RBC normally occurs by phagocytosis by the fixed macrophages of the spleen. After phagocytosis and subsequent disruption of the cell membrane, Hgb is converted to heme and globin. Iron is released from the heme moiety and either stored in the macrophage as ferritin or hemosiderin, or released into the circulation for transport back to the marrow. The remaining heme is converted to bilirubin, which is released by the macrophages into the systemic circulation where it complexes with albumin for transport to the hepatocytes; there, it is conjugated and excreted into the bile. In extravascular hemolytic anemias, RBC have a shortened life span, and the same mechanisms occur at an increased rate. About 1% of normal aging RBC are hemolyzed in the circulation, and free Hgb is released. This is quickly converted to Hgb dimers that bind to haptoglobin and are transported to the liver, where they are metabolized in the same manner as are products from RBC removed by phagocytosis. In intravascular hemolytic anemia, more RBC are destroyed in the circulation (hemoglobinemia) than can be bound to haptoglobin. The excess Hgb and, therefore, iron are excreted in the urine (hemoglobinuria). The principal metabolic pathway of RBC is glycolysis, and the main energy source in most species is glucose. The energy of ATP is used to maintain RBC membrane pumps so as to preserve shape and flexibility. The glucose not used in glycolysis is metabolized via a second pathway, the hexose monophosphate (HMP) shunt. No energy is produced via the HMP shunt; its principal effect is to maintain reducing potential in the form of reduced nicotinamide adenine dinucleotide phosphate (NADPH). Excessive oxidant stress may overload the protective HMP shunt or methemoglobin reductase pathways and, thereby, cause Heinz body hemolysis or methemoglobin formation, respectively. Hemolytic anemias caused by certain drugs, such as phenothiazine in horses or acetaminophen in cats, are examples of this mechanism. See also anemia, Anemia of Chronic Disease , Chicken Anemia Virus Infection: Introduction , Equine Infectious Anemia: Introduction , Hemobartonellosis , Autoimmune Hemolytic Anemia and Thrombocytopenia . Iron is the limiting factor in chronic blood loss. Hemolysis may be caused by toxins, infectious agents, congenital abnormalities, or antibodies directed against RBC membrane antigens. Decreased RBC production may result from primary marrow diseases (such as aplastic anemia, hematopoietic malignancy, or myelofibrosis) or from other causes such as renal failure, drugs, toxins, or antibodies directed against RBC precursors. White Blood Cells Phagocytes: Mononuclear phagocytes arise primarily from the marrow and are released into the blood as monocytes. They may circulate for hours to a few days before entering the tissues and differentiating to become macrophages. Granulocytes have a segmented nucleus and are classified according to their staining characteristics as neutrophils, eosinophils, or basophils. . Neutrophils circulate for only a few hours before travelling to the tissues. Lymphocytes: Lymphocytes are responsible for both humoral and cellular immunity. Lymphocyte production in mammals originates in the bone marrow. Some of the lymphocytes destined to be involved in cellular immunity migrate to the thymus and differentiate further under the influence of thymic hormones. These become “T cells” and are responsible for a variety of helper, suppressor, or cytotoxic immunologic functions. Most circulating lymphocytes are T cells, but many are also present in the spleen and lymph nodes. The B cells migrate directly to organs without undergoing modification in the thymus and are responsible for humoral immunity (antibody production). Thus, lymphoid organs have populations of both B and T lymphocytes. In the lymph nodes, follicular centers are primarily B cells, and parafollicular zones are primarily T cells. In the spleen, most of the lymphocytes of the red pulp are B cells, whereas those of the periarteriolar lymphoid sheaths are T cells. The humoral immune system is composed of B lymphocytes that produce antibodies of several classes. When sensitized B lymphocytes encounter antigen, they undergo blast transformation, divide, and differentiate into plasma cells that produce antibody. Therefore, each B lymphocyte initially stimulated produces a clone of plasma cells, all producing the same specific antibody. Merck Veterinary Manual - Summary

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Antibody molecules (immunoglobulins) fall into several classes, each with its own functional characteristics. For example, IgA is the principal antibody of respiratory and intestinal secretions, IgM is the first antibody produced in response to a newly recognized antigen, IgG is the principal antibody of the circulating blood, and IgE is the principal antibody involved in allergic reactions. Helper T cells are required for full expression of a humoral immune response. Suppressor T cells dampen the production of a given antibody. Natural killer cells, which are a class of lymphocyte distinct from T cells and B cells, destroy foreign cells (eg, neoplastic cells) even without prior sensitization. Lymphocyte response in disease may be appropriate (activation of the immune system) or inappropriate (immunemediated disease and lymphoproliferative malignancies). See also immune system et seq. Immune-mediated disease results from failure of the immune system to recognize host tissues as self. For example, in immune-mediated hemolytic anemia, antibodies are produced against the host's own RBC. Platelets Platelets form the initial hemostatic plug whenever hemorrhage occurs. They also are the source of phospholipid, which is needed for coagulation factors to interact to form a fibrin clot. Platelets are produced in the bone marrow from megakaryocytes, under the influence of thrombopoietin. Platelet production begins with invagination of the megakaryocyte cell membrane and the formation of cytoplasmic channels and islands. Platelet disorders are either quantitative (thrombocytopenia or thrombocytosis) or qualitative (thrombocytopathy). Thrombocytopenia is one of the most common bleeding disorders of animals. In general, platelet counts must fall to 75% of canine lymphomas are of B-cell origin, and 10-20% are of T-cell origin. B-cell neoplasms are associated with better response and longer remission and survival times than T-cell neoplasms. There is a strong correlation between some T-cell neoplasms and hypercalcemia (especially with T-cell lymphomas involving the thymus and bone marrow), and these tumors are associated with poorer response rates and shorter survival and remission times. Treatment: Most treatment regimens use a combination of cyclophosphamide, vincristine, and prednisone. The addition of asparaginase or adriamycin has improved response rates and survival times. Adverse reactions include bone marrow suppression, increased susceptibility to infection, and hemorrhagic cystitis from cyclophosphamide. Use of antibiotics in an attempt to prevent these occurrences is controversial. Chemotherapy is generally divided into an induction phase, in which a combination of drugs is administered intensively over a short period of time, and a maintenance phase. Maintenance: The diffuse alimentary form of lymphosarcoma often responds poorly to chemotherapy. However, if the lesion is localized to a segment of the intestine, surgical resection followed by chemotherapy should be performed. In this case, the prognosis is guarded to fair for long-term response. Treatment of lymphoblastic leukemia has been less successful, with a median survival time of 200 times/min in the cat, and 60-160 times/min in the dog. In general, the larger the species, the slower the rate of SA node discharge and the slower the heart rate. The rate of SA node discharge increases, often to nearly 300 beats/min, when norepinephrine is released from the sympathetic nerves and binds to the β1-adrenoreceptors on the SA node. This cardioacceleration may be blocked by βadrenergic blocking agents (eg, propranolol, atenolol, metoprolol). The rate of SA node discharge decreases when acetylcholine released by the parasympathetic (vagus) nerves binds to the cholinergic receptors on the SA node. This vagally mediated cardiodeceleration may be blocked by a parasympatholytic (vagolytic) compound (eg, atropine, glycopyrrolate). In quiet, healthy dogs, the heart rate is usually irregular. It increases during inspiration and decreases during expiration. This is termed respiratory sinus arrhythmia and results from decreased vagal activity during inspiration and increased vagal activity during expiration. Therefore, vagolytic compounds, as well as excitement, pain, or fever, usually abolish or diminish respiratory sinus arrhythmia. Heart rate is also inversely related to systemic arterial blood pressure. When blood pressure increases, heart rate decreases; when blood pressure decreases, heart rate increases. This relationship is known as the Marey reflex and occurs by the following mechanisms. When high-pressure arterial baroreceptors in the aortic and carotid sinuses detect the fall in blood pressure, they send increased afferent volleys to the medulla oblongata, which decreases vagal efferents to the SA node and causes the heart rate to increase. When blood pressure increases, heart rate slows due to increased vagal efferents to the SA node. In heart failure, the baroreceptors “believe” that blood pressure is too low, even though this may not be so. Thus, the baroreceptors initiate compensatory mechanisms (eg, arterial and arteriolar constriction, venous constriction, increase in heart rate) designed to increase blood pressure that, unfortunately, injure the heart. Whatever speeds or slows the rate of discharge of the SA node also speeds or slows conduction through the AV node. Thus, when heart rate is fast, the PQ is short; when heart rate is slow, the PQ is long. Force of Ventricular Contraction: The force with which the ventricles contract is determined by three factors: 1) the end-diastolic volume or preload, which is the volume of blood within the ventricles just before they begin to contract, 2) myocardial contractility or the inotropic state, which is the rate of cycling of the microscopic contractile units of the myocardium, and 3) the afterload, which is the interference to ejection of blood from the ventricle into and through the arterial tree. The afterload is measured as the peak tension the myocardium must generate to eject blood. The preload is the difference in end-diastolic pressure between the ventricle and the pleural space, divided by the stiffness of the ventricular myocardium. The preload is regulated predominantly by low-pressure volume receptors in the heart and large veins. When these receptors are stimulated by an increase in blood volume or by distention of the structures the receptors occupy, the body responds by making more urine and by dilating the veins—an attempt to decrease blood volume and lower the pressures in the veins responsible for venous distention. Myocardial contractility is determined by the rate of liberation of energy from ATP, which is determined, in part, by the amount of norepinephrine binding to β-1 adrenergic receptors in the myocardium. The afterload is determined by the relative stiffness of the arteries and by the degree of constriction or dilatation of the arterioles, both of which are determined by the degree of constriction or relaxation of the arterial and arteriolar vascular smooth muscle. The tone of vascular smooth muscle depends on many factors, some of which constrict the muscle (eg, α-1, angiotensin II, vasopressin, endothelin) and some of which relax the muscle (eg, β-2, atriopeptin, bradykinin, adenosine, nitric oxide). Afterload and peak tension are also determined by the preload and thickness of the ventricular wall just before ejecting. In fact, peak tension is equal to the preload times the diastolic arterial blood pressure, all divided by the end-diastolic wall thickness of the ventricle. Oxygen and the Myocardium: The amount of oxygen delivered to the heart depends on how well the lung functions, how much hemoglobin (Hgb) is present to carry the oxygen, and how much blood carrying the Hgb flows through the heart muscle via the coronary arteries. The amount of oxygen consumed by the heart is termed myocardial oxygen consumption. It is determined, principally, by heart rate, myocardial contractility, and afterload. Myocardial oxygen consumption is higher when each of the determinants is higher, and lower when each of the determinants is lower. Both heart rate and myocardial contractility are

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increased by β-l adrenergic stimulation (or by norepinephrine) and are decreased by an increase in parasympathetic stimulation; therefore, autonomic activity also influences myocardial oxygen consumption. In heart failure, inappropriate handling of calcium may be the most important factor that leads to both reduced force of contraction and reduced rate of relaxation (ie, reduced systolic as well as diastolic function). Interference to the Flow of Blood: Most (80%) of the interference to blood flow is from the degree of constriction or dilatation of the arterioles, termed the vascular resistance; however, some interference is from the stiffness of the portion of the great arteries closest to the ventricles, termed the impedance. One of the most important features of heart failure that leads to morbidity is increased resistance of arterial, arteriolar, and venous smooth muscle. This results because of increased angiotensin II and vasopressin due to (incorrect) compensatory feedback from the high-pressure baroreceptors to the medulla that blood pressure is too low. If the left ventricle is unable to eject a normal stroke volume or cardiac output, it is reasonable that the ventricular function might be improved by decreasing both vascular resistance and impedance—which is precisely why drugs that relax vascular smooth muscle are useful. Principles Of Therapy: Overview The following are general goals of therapy for heart disease. 1) Chronic stretch on myocardial fibers should be minimized because chronic stretch injures and irritates fibers, causes them to consume excess quantities of oxygen, and leads to their death and replacement by fibrous connective tissue (remodeling). 2) Edema fluid should be removed because it makes the lung wet, heavy, and stiff, and causes ventilation-perfusion inequalities and fatigues muscles of ventilation. 3) The circulation should be improved and the amount of regurgitation (most often mitral regurgitation) decreased. Improved circulation enhances blood flow to important organs, and reducing mitral regurgitation decreases stretch on the left atrium and pulmonary veins, decreases pulmonary capillary pressure, and decreases edema formation. 4) Heart rate and rhythm should be regulated. A heart beating too slowly fails to eject enough blood. A heart beating too rapidly does not have time and consumes too much oxygen at a time when there is too little coronary blood flow. A heart beating too irregularly may deteriorate into ventricular fibrillation and sudden death. 5) Oxygenation of the blood should be improved. Inadequate oxygenation leads to inadequate energy to fuel both contraction and relaxation of the myocardium. Inadequate oxygenation of the myocardium may also lead to arrhythmia. 6) β1-adrenergic receptors should be “up regulated.” “Down regulation” of β1-adrenergic receptors interferes with the ability to fight diseases of other organ systems. 7) The likelihood of thromboembolism should be minimized. Cats with hypertrophic cardiomyopathy may shed emboli from the enlarged left atrium, which may plug up major arterial branches and lead to ischemia and death. 8) Mature heartworms and microfilariae should be killed. Mature heartworms may initiate severe changes in the pulmonary arteries that ultimately impede blood flow through the lung. The ultimate goals of therapy for cardiovascular disease are achieved when the animal can be classified as functional Class I, the respiratory and heart rates are not increased at rest, and there is a respiratory sinus arrhythmia. Common Therapeutic Agents Furosemide is a diuretic that decreases resorption of provisional urine at the loop of Henle. It is also a venodilator when used IV. Theophylline is a bronchodilator and strengthens the muscles of ventilation. Chlorothiazide is a diuretic that decreases resorption of provisional urine at the distal convoluted tubule. It is used when furosemide diuresis either stops or is inadequate. (Note: All thiazides possess similar actions.) Spironolactone is a potassium-sparing diuretic that blocks aldosterone; it exerts its diuretic effect at the distal convoluted tubule. Amiloride and triamterine have similar modes of action. Digitalis glycosides exert their effects by inhibiting membrane Na-K-ATPase. Digoxin increases the force of myocardial contraction, slows the heart rate, and improves baroreceptor function. It also strengthens muscles of ventilation. Enalapril is an angiotensin-converting enzyme inhibitor that blocks the conversion of angiotensin I to angiotensin II. It reduces afterload, thereby improving cardiac output and reducing mitral regurgitation. It also improves baroreceptor function and is a venodilator. Procainamide is an antiarrhythmic compound used to suppress ventricular arrhythmias. It is used most often for ventricular arrhythmias that are not life-threatening; it is given most often orally. Quinidine is similar to procainamide but is the drug of choice for treating atrial fibrillation in horses. Lidocaine is used only IV for emergency ventricular arrhythmias. Mexilitine is an oral compound similar to lidocaine. Atenolol, propranolol, and metoprolol are β-andrenergic blockers that slow the heart rate, suppress arrhythmias, and “up regulate” adrenergic receptors. Diltiazem is a calcium-channel blocker that is useful for slow ventricular rate in animals with atrial fibrillation. It is also used to decrease myocardial Merck Veterinary Manual - Summary

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stiffness in cats with hypertrophic cardiomyopathy. Verapamil is also a calcium-channel blocker, but it reduces myocardial contractility more than diltiazem. Sotolol and amiodorone are antiarrhythmic compounds useful for managing all forms of arrhythmias, but there is relatively little clinical experience with them. Atropine and glycopyrrolate block the effects of the vagus nerve on the SA node. Because the vagus nerve slows discharge of the SA node and heart rate, these compounds speed heart rate and may be useful when the heart beats too slowly. Nitroglycerine is a venodilator that is usually applied in a paste form to the skin inside of the earflap or thigh. By dilating peripheral veins, blood pools in those veins, and left ventricular preload and pulmonary edema are decreased. Aspirin and coumadin are anticoagulants that may prevent thromboembolism in cats with cardiomyopathy. Taurine and l-carnitine are amino acids useful in preventing dilated cardiomyopathy in cats (taurine) and, in a limited number of dogs (l-carnitine). Thiacetarsamide is used to kill mature heartworms. Ivermectin and milbemycin are used to kill microfilariae. Anomalies Of Derivatives Of The Aortic Arches: Overview Patent Ductus Arteriosus In fetal life, oxygenated blood within the main pulmonary artery is shunted into the descending aorta through the ductus arteriosus, thereby bypassing the nonfunctional lungs. At birth, several factors mediate closure of the ductus, which effects separation of the systemic and pulmonary circulatory systems. Inflation of the lungs allows the pulmonary circulation to function as a low pressure system, and closure of the ductus prevents shunting of blood from the high pressure systemic circulatory system into the pulmonary artery. Pathophysiology: Persistence or patency of the ductus with an otherwise normal systemic and pulmonary circulatory system results in significant shunting of blood from left to right, ie, systemic to pulmonary. Because the pressure within the aorta is always higher than that of the pulmonary artery, shunting is continuous and produces the classic continuous, machinery-like murmur. The result is a volume overload of the pulmonary arteries and veins, left atrium, and left ventricle. Dilatation of these structures becomes evident. Left atrial and left ventricular dilatation may result in cardiac arrhythmias. Chronic volume overloading and dilatation of the left-sided cardiac chambers usually result in signs of left-sided congestive heart failure (pulmonary edema, cough, fatigue). Therefore, most untreated cases develop refractory congestive heart failure. Animals with a small ductus may reach adulthood without signs of heart failure but are at an increased risk of endocarditis. In a few untreated cases, increased pulmonary blood flow induces pulmonary vasoconstriction and development of pulmonary hypertension, which has several important implications. Shunting through the ductus slows and reverses, which causes disappearance of the murmur and occurrence of caudal cyanosis; the right ventricle becomes dilated and hypertrophied as a result of pulmonary vasoconstriction; and perfusion of the kidneys with desaturated blood causes excessive release of erythropoietin and subsequent polycythemia. Thus, if the ductus is shunting right to left, clinical signs of right ventricular failure (ascites, fatigue) and polycythemia (exercise intolerance, seizures) will predominate. In some cases, a right-to-left shunt is present at birth secondary to a patent ductus and retention of pulmonary vasculature (congenital pulmonary hypertension). Clinical Findings and Treatment: In animals with a PDA that shunts from left to right, a prominent, continuous, machinery-like murmur is present. The systolic component is loudest, heard best over the aortic valve area, and often associated with a precordial thrill. Most young animals do not demonstrate clinical signs. Those with a large shunt and older animals often have signs of left-sided congestive heart failure, eg, cough, tachypnea, exercise intolerance, and weight loss. Consistent electrocardiographic features include evidence of left ventricular and left atrial enlargement. Radiography demonstrates left atrial and left ventricular enlargement, prominent pulmonary vessels, aortic and pulmonic aneurysmal dilatations, and variable degrees of pulmonary edema. Echocardiography is not crucial in the diagnosis of PDA but is valuable in ruling out concurrent congenital cardiac defects. Surgical ligation of the ductus is curative and indicated in all cases deemed satisfactory anesthetic risks, considering the risk of congestive heart failure and endocarditis in untreated cases. If present, congestive heart failure should be medically managed (with diuretics, vasodilators, etc) before anesthesia and surgery. In animals with a PDA that shunts from right to left, there is usually a history of lethargy, exercise intolerance, and collapse. Careful examination may reveal differential cyanosis. Therapy involves control of polycythemia through periodic phlebotomies. Long-term prognosis is poor. Persistent Right Aortic Arch In this vascular ring anomaly, the right aortic arch persists, which causes obstruction of the esophagus at the level of the heart base. The esophagus is encircled by the persistent arch on the right, by the ligamentum arteriosum to the left and dorsally, and by the base of the heart ventrally. These congenital defects do not cause clinical signs referable to the cardiovascular system—signs of regurgitation and aspiration pneumonia predominate.

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Aortic Stenosis Left ventricular emptying may be obstructed at three locations: 1) subvalvular, consisting of a fibrous ridge of tissue within the left ventricular outflow tract; 2) valvular; and 3) supravalvular or obstruction distal to the aortic valve. The most common form in the dog is subaortic stenosis. Breed predilections have been identified for Boxers, Golden Retrievers, and Newfoundlands. Pathophysiology: Aortic stenosis induces left ventricular hypertrophy, the degree of which depends on the severity of the stenosis. In severe cases, left ventricular output may be decreased, especially during exercise. The major ramification of left ventricular hypertrophy is the creation of areas of myocardium with poor perfusion. Myocardial ischemia is a major factor in the development of serious life-threatening ventricular arrhythmias. Clinical Findings and Treatment: There may be a history of syncope and exercise intolerance. Animals with no history of illness may die suddenly, and the defect is first detected at necropsy. The degree of left ventricular hypertrophy and ejection velocity through the defect allow determination of severity and need for intervention. Treatment options include balloon valvuloplasty and surgical resection. The use of β-adrenergic blockers (propranolol, atenolol) have been advocated in animals experiencing syncope to reduce the frequency of arrhythmias. Affected animals should not be used for breeding. Pulmonic Stenosis Pulmonic stenosis is a common congenital cardiac defect in dogs. It results in obstruction to right ventricular emptying due, in most cases, to partial fusion and dysplasia of the pulmonic valve cusps. Pathophysiology: The right ventricle must generate increased pressure during systole to overcome the stenosis, which often leads to dramatic right ventricular hypertrophy. As the right ventricle hypertrophies, its compliance diminishes, which leads to increased right atrial pressures and venous congestion. The jet of blood passing through the stenosis deforms the wall of the main pulmonary artery and results in a poststenotic dilatation. In severe cases, rightsided congestive failure is present. Clinical Findings and Treatment: Affected animals may have a history of failure to thrive and exercise intolerance. Right-sided congestive heart failure may be present and is characterized by ascites or peripheral edema. A prominent ejection-type systolic murmur is present and heard best at the pulmonic valve area. A corresponding precordial thrill is usually present. Jugular distention and pulsations may also be present. Radiographic abnormalities include right ventricular enlargement, an aneurysmal dilation of the main pulmonary artery, and diminished pulmonary vasculature. Animals with moderate or severe pulmonic stenosis will benefit from balloon valvuloplasty or surgical resection. Palliative therapy with diuretics and vasodilators should be initiated if right-sided congestive heart failure is present. Atrial Septal Defects A communication between the atria may be the result of a patent foramen ovale or a true atrial septal defect. During fetal life, the foramen ovale, a flapped oval opening of the interatrial septum, allows shunting of blood from the right atrium to the left atrium, in order to bypass the nonfunctional lungs. At birth, the drop in right atrial pressure causes the foramen ovale to close and shunting to cease. Increased right atrial pressure may reopen the foramen ovale and allow shunting to resume. A true atrial septal defect is a consistent opening of the interatrial septum, which allows blood to shunt from the atrium with the greater pressure. Ventricular Septal Defects Ventricular septal defects are most commonly located in the membranous portion (subaortal) of the septum, near the level of the atrioventricular valves. Tetralogy of Fallot Tetralogy of Fallot is the most common defect that produces cyanosis. It results from a combination of pulmonic stenosis, high ventricular septal defect, right ventricular hypertrophy, and varying degrees of dextroposition and overriding of the aorta. The right ventricular hypertrophy is secondary to the obstruction to right ventricular outflow. The pulmonic stenosis component may be valvular or infundibular, or both. Canine breeds predisposed to tetralogy of Fallot include the Keeshond, English Bulldog, miniature Poodle, miniature Schnauzer, and Wirehaired Fox Terrier. A polygenic trait has been found in the Keeshond. This defect has been recognized in other breeds of dogs and in cats. Pathophysiology:

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The hemodynamic consequences of tetralogy of Fallot depend primarily on the severity of the pulmonic stenosis and on the size of the ventricular septal defect. The direction and magnitude of the shunt through the septal defect depends on the degree of right ventricular obstruction. If the pulmonic stenosis is mild and right ventricular pressures are only modestly increased, blood will shunt primarily from left to right. When pulmonic stenosis is severe, the increased right ventricular pressures will result in shunting from right to left. Consequences include reduced pulmonary blood flow (resulting in fatigue, shortness of breath) and generalized cyanosis (resulting in polycythemia, weakness). Due to shunting of venous blood into the aorta and consequent hypoxia, the kidneys are stimulated to release erythropoietin, which results in polycythemia ( Polycythemia: Introduction). The increased blood viscosity associated with polycythemia can have significant hemodynamic effects, such as sludging of blood and poor capillary perfusion. Animals with severe polycythemia often have a history of seizures. Clinical Findings and Treatment: Typical historical features include stunted growth, exercise intolerance, cyanosis, collapse, and seizures. A precordial thrill may be felt in the area of the pulmonic valve, and in most cases, a murmur of pulmonic stenosis is present. The intensity of the murmur is attenuated when severe polycythemia is present. Overriding (rightward displacement) of the aortic root, right ventricular hypertrophy, and a ventricular septal defect are evident. β-Adrenergic blockade has been used to reduce the dynamic component of right ventricular outflow obstruction and to attenuate β-adrenergic-mediated decreases in systemic vascular resistance. Increases in systemic vascular resistance will lower the magnitude of shunting. Polycythemia should be controlled by periodic phlebotomy. When the PCV exceeds 68, intervention is indicated. Up to 20 mL/kg of blood can be removed and replaced with a crystalloid solution (eg, lactated Ringer's or saline). The prognosis is guarded. Surgical correction of tetralogy of Fallot is rarely performed due to the attendant mortality and expense. Mitral Valve Dysplasia Congenital malformation of the mitral valve complex (mitral valve dysplasia) is a common congenital cardiac defect in the cat. Canine breeds predisposed are Bull Terriers, German Shepherd Dogs, and Great Danes. Mitral valve dysplasia results in mitral insufficiency and systolic regurgitation of blood into the left atrium. Any component of the mitral valve complex (valve leaflets, chordae tendineae, papillary muscles) may be malformed. Often, more than one component is defective. Pathophysiology: Malformation of the mitral valve complex results in significant valvular insufficiency. Chronic mitral regurgitation leads to volume overload of the left heart, which results in dilatation of the left ventricle and atrium. When mitral regurgitation is severe, cardiac output decreases, which results in signs of cardiac failure. Dilatation of the left-sided chambers predisposes affected animals to arrhythmias. In some cases, malformation of the mitral valve complex causes a degree of valvular stenosis as well as insufficiency. Clinical Findings and Treatment: Affected animals usually display signs of left-sided heart failure, including weakness, cough, and exercise intolerance. A holosystolic murmur of mitral regurgitation is prominent at the left cardiac apex. Thoracic radiographs reveal severe left atrial enlargement. Left ventricular enlargement is also present, and pulmonary veins are congested. Prognosis for animals with clinical signs is poor. Tricuspid Dysplasia Congenital malformation of the tricuspid valve complex is seen occasionally in dogs. Breeds predisposed are Labrador Retrievers and German Shepherd Dogs. Tricuspid dysplasia results in tricuspid insufficiency and systolic regurgitation of blood into the right atrium . Pathophysiology: Malformation of the tricuspid valve results in significant valvular insufficiency. Chronic tricuspid regurgitation leads to volume overload of the right heart, which results in dilation of the right ventricle and atrium. Pulmonary blood flow may be decreased and result in fatigue and tachypnea. As the pressure in the right atrium increases, venous return is impaired, which results in ascites. Clinical Findings and Treatment: Clinical signs correlate with the severity of the defect. Affected animals usually display signs of right-sided heart failure, including jugular distention and pulsation, edema, ascites, tachypnea, and exercise intolerance. Atrial arrhythmias, especially paroxysmal atrial tachycardia, are common and become serious enough to cause death. Thoracic radiographs reveal severe right atrial and right ventricular enlargement. The caudal vena cava may be significantly enlarged. Prognosis for animals with clinical signs is guarded. Periodic abdominocentesis may be needed to control peritoneal effusions. Diuretics, vasodilators, and digoxin may also be indicated. Cardiac Insufficiency And Failure: Overview Merck Veterinary Manual - Summary

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Heart disease must be distinguished from heart failure. Heart disease refers to a condition in which there is an abnormality of the heart, whereas heart failure exists when the heart is unable to meet the circulatory demands of the body. Most often, the development of clinical signs such as cough, edema, and tachypnea indicate the presence of heart failure. Signs of heart failure may be more pronounced in active animals because their circulatory demands are higher; likewise, signs of heart failure may be delayed in sedentary animals because their cardiovascular systems are rarely challenged. In general, heart failure may occur secondary to decreases in stroke volume or to abnormal heart rates. Decreases in Stroke Volume: Stroke volume (the amount of blood ejected each cycle from either ventricle) may decrease secondary to reductions in preload, impaired contractility, increased afterload, or inadequate valvular function. A significant reduction in preload (analogous to venous return) may result in a decreased stroke volume and consequent heart failure. Examples include shock secondary to hypovolemia or hemorrhage, excessive use of diuretics, pericardial effusion with tamponade, and hypertrophic cardiomyopathy. Impaired contractility decreases stroke volume and can precipitate congestive heart failure; this occurs in dilated cardiomyopathy of large-breed dogs and in cardiomyopathy of overload (myocardial failure secondary to unligated PDA or chronic valvular disease). When there is an increased afterload, a greater than usual deterrent to ventricular emptying exists, which may result in partial ventricular emptying and a decreased stroke volume; this occurs in severe hypertension (pulmonary or systemic) and in aortic or pulmonic stenosis. The AV valves (mitral and tricuspid valves) normally prevent blood from rushing back into the atria during ventricular contraction. When valve function is inadequate or insufficient, blood reenters the atria causing atrial dilation, reducing the amount of forward flow, and consequently decreasing stroke volume. The most common causes of valvular insufficiency are degenerative valve disease (endocardiosis) and infective endocarditis. The pathologic changes can be predicted—when there is insufficiency of the tricuspid valve due to infective endocarditis, tricuspid valvular insufficiency would be expected, as well as right atrial enlargement, vena caval congestion, and ascites. Left-sided Congestive Heart Failure: Left atrial pressure rises whenever left ventricular emptying is encumbered or mitral insufficiency exists. Pulmonary venous flow is impeded and pulmonary venous pressure is increased, which ultimately leads to the formation of pulmonary edema. Cough, which is a consistent feature of left-sided CHF, typically follows activity or is nocturnal. It is initially caused by edema-induced distortion of the pulmonary interstitium. As pulmonary edema worsens, fluid enters the alveoli and airways, causing the cough to increase in intensity and frequency, and rales are present on auscultation. Other signs of pulmonary edema secondary to left-sided CHF include tachypnea, orthopnea (labored breathing while recumbent), and dyspnea. Other clinical signs of left-sided CHF include exercise intolerance, tachycardia, and occasionally weight loss. Right-sided Congestive Heart Failure: An increased in right atrial pressure impedes venous flow from the cranial and caudal vena cava, resulting in systemic venous congestion. Clinically, this is manifested as jugular venous distention, subcutaneous edema, and ascites. The pattern of subcutaneous edema is fairly species-specific—it is uncommon in dogs, generally involves the submandibular and brisket area in cattle, and is seen in the preputial and mammary area in horses. Cats rarely have subcutaneous edema but often develop pleural effusion (hydrothorax). Generalized Congestive Heart Failure: Diseases affecting one side of the heart often precipitate failure of the other side and cause signs of both left- and rightsided CHF. As congestion worsens, left-sided signs predominate due to the severe consequences of pulmonary edema. Diet: A sodium-restricted diet is recommended Diuretics: Diuretics are the mainstay therapy in the management of animals with pulmonary edema. Of the several types of diuretics available (loop diuretics, thiazides, potassium-sparing), the loop diuretics (eg, furosemide) are most commonly used. Furosemide is a potent diuretic that inhibits the resorption of sodium, potassium, chloride, and hydrogen ion from the ascending limb of the loop of Henle—as these ions are excreted, water follows. The dose and frequency of furosemide required depends on the severity of pulmonary edema and the degree of respiratory distress. Side effects of furosemide may include volume depletion and prerenal azotemia, hypokalemia, and metabolic alkalosis (via renal loss of hydrogen). Vasodilators: Vasoconstriction is an important compensatory mechanism that occurs when cardiac output is compromised. ACE inhibitors are indicated in the treatment of mild to severe left-sided CHF in the dog. By reducing vasoconstriction and excessive systemic vascular resistance, ACE inhibitors improve cardiac output and reduce regurgitant fraction when mitral insufficiency is present. The use of vasodilators (eg, enalapril) has become an important part of treatment strategy in animals with heart disease. Clinically, the most significant concern is the development of azotemia secondary to reduced renal perfusion. Although the risk is low, it is recommended that renal function be determined before ACE inhibitor therapy is started. Other ACE inhibitors used (but not approved) include captopril (0.5-1.0 mg/kg, t.i.d.) and benazepril (0.25 mg/kg, s.i.d.). Unlike

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enalapril and captopril, benazepril is excreted by the liver and may be useful in animals with heart failure and renal insufficiency. Although enalapril and captopril are most commonly used, there are other vasodilators available. Hydralazine directly dilates arterioles presumably by increasing vasodilatory prostaglandins (PGI2). It is specific for arteriolar vasodilation and has little effect on venous tone. Hydralazine decreases pulmonary capillary wedge pressure (similar to left atrial pressure) and increases cardiac index. Hypotension and tachycardia are common side effects, and it is recommended that animals be hospitalized and carefully monitored (blood pressure, electrocardiography) when instituting therapy. If hypotension occurs, hydralazine should be discontinued for 24 hr and then resumed at one-half the previous dosage. Persistent tachycardia should also prompt a reduction in the dosage; occasionally, digoxin or a β-adrenergic blocker are required to control heart rate. Nitroglycerin is a useful venodilator in cases of acute pulmonary edema. By increasing venous capacitance, preload is decreased and blood volume is essentially shifted from the thorax to the abdomen. One major advantage is that because nitroglycerin can be applied to the skin (it is transcutaneously absorbed), administration is not stressful to the animal. The dose of 2% nitroglycerin ointment is 0.3-0.6 cm/kg, applied every 4-6 hr. Gloves should be worn by the person applying the ointment, and care should be taken to avoid contact with the ointment once it has been applied. Side effects are infrequent, but excessive use may result in hypotension, lethargy, and vomiting. Sodium nitroprusside can also be used in acute congestive heart failure because it causes rapid vasodilation. Unlike nitroglycerin, sodium nitroprusside is a balanced vasodilator, causing dilatation of both arterioles and veins. The result is a decrease in both systemic vascular resistance and preload and an increase in cardiac output. Because the half-life is very short, sodium nitroprusside must be administered as a constant rate infusion. It is commonly administered in conjunction with an infusion of dobutamine, a positive inotropic agent (see below). Dobutamine further increases cardiac output and mitigates the hypotensive effects of sodium nitroprusside. Positive Inotropic Agents: These agents increase cardiac contractility and are indicated when myocardial function, specifically contractility, is impaired. Dilated cardiomyopathy and chronic, advanced degenerative valve disease are two common indications in small animals. The digitalis glycosides are the most often used positive inotropic agents. Digoxin and digitoxin increase the intracellular concentration of calcium causing a modest increase in cardiac contractility. Digoxin is the most commonly used digitalis glycoside. Digoxin is renally excreted and therefore should be used with caution in animals with renal insufficiency, if at all. In these animals, digitoxin is the preferred digitalis glycoside because it is metabolized by the liver. Side effects of digitalis are common because the therapeutic index is narrow. Common side effects include depression, anorexia, vomiting, diarrhea, and cardiac arrhythmias. Dobutamine is a synthetic catecholamine that primarily stimulates β1-adrenergic receptors. Through stimulation of these receptors, dobutamine mediates an increase in cardiac contractility. Its positive inotropic effects are much greater than those of the digitalis glycosides. The major indication in veterinary medicine is severe myocardial failure secondary to dilated cardiomyopathy, although it may be used in dogs with degenerative valve disease and concurrent myocardial failure. Dobutamine can cause cardiac arrhythmias—therefore, ECG monitoring is critical during the infusion. Dobutamine also increases conduction of the AV node; therefore, if atrial fibrillation is present, the ventricular response may increase excessively. Other Therapy: Deficiency of L-carnitine has been documented in a family of Boxers with dilated cardiomyopathy, and supplementation resulted in an improvement in cardiac contractility. L-carnitine plays a pivotal role in fatty acid metabolism and myocardial energy production. Compensatory Mechanisms in Congestive Heart Failure When decreased flow or pressure is sensed, there is an immediate withdrawal of parasympathetic tone and activation of the sympathetic nervous system. These changes result in an immediate increase in heart rate and cardiac contractility as well as constriction of arterioles and veins. Decreased blood pressure along with increased sympathetic tone activates the reninangiotensin-aldosterone axis. Renin is released by the juxtaglomerular apparatus of the kidney and converts angiotensinogen to angiotensin I, an inactive decapeptide. The two terminal amino acids of this peptide are cleaved by angiotensinconverting enzyme (an enzyme found in high levels in pulmonary endothelial tissue) to form angiotensin II, a remarkably potent vasoconstrictor. Angiotensin II also increases thirst, promotes sodium retention by the kidneys, and stimulates secretion of aldosterone by the adrenal cortex, resulting in further sodium and water retention. In the short-term, these compensatory mechanisms are beneficial and help to restore fluid volume and blood pressure. They are life-saving in animals with transient circulatory collapse (eg, hemorrhage) but become maladaptive when stimulated by chronic conditions (eg, heart disease). Sustained activation of the sympathetic nervous system increases myocardial oxygen demand, predisposes the heart to arrhythmias, and may cause myocardial damage (necrosis of myocytes). Persistent sodium and water retention hastens the development of pulmonary edema. Chronic vasoconstriction

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strains the heart by either increasing afterload or impeding ventricular emptying. As these compensatory mechanisms become deleterious, cardiac output decreases, further stimulating these processes, ie, the “vicious cycle of heart failure.” Therapy of Congestive Heart Failure Medical management of CHF is aimed at reversing or controlling the deleterious effects of the underlying disease. These effects may include pulmonary congestion and edema, cardiac arrhythmias, reduced cardiac output, and excessive vasoconstriction. In severely affected animals, specific medications may be needed to control each of these complications.

The Endocardium Infective Endocarditis: Infection of the endocardium typically involves one of the cardiac valves, although mural endocarditis may occur. It is thought that some sort of endothelial defect must be present for infective endocarditis to develop. When the endothelium is partially eroded and underlying collagen exposed, platelets adhere and produce a local thrombus. Blood-borne bacteria may become enmeshed in this thrombic lattice, resulting in a localized infection. This infection, through its own enzymes and host mediators, causes a progressive destruction of the valve, resulting in valvular insufficiency. In dogs, the aortic valve is most commonly affected, resulting in aortic insufficiency. The left ventricle cannot tolerate the constant back flow from the insufficient valve and soon fails. Infective endocarditis of the AV valves (tricuspid and mitral) also occurs but is better tolerated than aortic endocarditis. In horses, the mitral valve is most commonly affected, while the tricuspid valve is most frequently involved in cattle. In cats, infective endocarditis is rare, and there are no breed predilections. In dogs, German Shepherd Dogs and other large-breed dogs are typically affected; there is a significant predilection for males (72%), and the mean age is 5 yr. Bacteria released from the infected valve enter the circulation and colonize other organs; therefore, infective endocarditis can produce a wide spectrum of clinical signs that may be neurologic, GI, urologic, orthopedic, or cardiovascular in nature. A chronic, fluctuating fever is usually present. Shifting leg lameness may occur. Malaise and weight loss are present in almost all cases. If a right-sided valve is affected (tricuspid, pulmonic), ascites and jugular pulsations may be present. A murmur is present in most cases, the exact type depending on the valve involved. When there is aortic endocarditis, a soft diastolic murmur is present, heard best over the left heart base, and arterial pulses are bounding. Mitral endocarditis results in a murmur similar to that caused by degenerative valve disease, ie, a prominent systolic murmur heard best over the left cardiac apex. Bacteria most often isolated from affected small animals include Streptococcus , Staphylococcus , Escherichia coli , and Klebsiella . Streptococcus and Actinobacillus equuli are the most common isolates of horses. A complete blood count often shows a neutrophilic leukocytosis. Radiography demonstrates cardiac chamber enlargement, depending on the location of the involved valve. If the aortic or mitral valve is affected, there will be left atrial and left ventricular dilatation. Evidence of left-sided failure may be seen as an increase in the interstitial densities and an alveolar pattern in the lungs. If the tricuspid or pulmonic valve is affected, right-sided chamber enlargement is expected. Diskospondylitis is a common sequela of infective endocarditis in dogs and is characterized by irregular, lytic vertebral endplates. Echocardiography is the ideal test to definitively diagnose infective endocarditis. The affected valve is easily detected. The height of the R waves may be increased (suggestive of left ventricular enlargement) and the width of the P wave increased (suggestive of left atrial enlargement). Therapy must be directed at controlling the CHF, sterilizing the lesion, and stopping spread of infection. The prognosis is much more favorable when infection is limited to one of the atrioventricular valves. Controlling CHF requires the use of diuretics (eg, furosemide), vasodilators (eg, enalapril), and digoxin if there is a rapid rate, supraventricular arrhythmias, or decreased contractility. Initially, parenteral antibiotics are indicated for 1-2 wk, followed by oral antibiotics for 6-8 wk. Bactericidal antibiotics should be used initially and changed, if needed, based on results of sensitivity studies. The most common combinations are ampicillin and gentamicin or cephalothin and gentamicin (renal function should be monitored). Degenerative Valve Disease (Endocardiosis): This acquired disease is characterized by degeneration and fibrosis of the cardiac valves. As endocardiosis progresses, the affected valve becomes increasingly insufficient. Insufficiency of the mitral valve allows blood to jet back into the left atrium during ventricular contraction, which increases the pressure within the left atrium, which decreases venous flow from the lungs. This results in pulmonary venous congestion and ultimately pulmonary edema. In addition, as the left atrium dilates, the likelihood that atrial arrhythmias (atrial premature contractions, atrial fibrillation) will occur is high, further decreasing cardiac output. The constant jetting of blood from the high-pressure left ventricle physically damages the endocardium of the left atrium and, in chronic cases, may result in left atrial rupture. The decrease in the amount of blood ejected by the left ventricle (cardiac output) forces several compensatory mechanisms into action. The body responds to decreases in cardiac output by increasing sympathetic tone and activating angiotensin-converting enzyme (ACE). On a chronic basis, these compensatory mechanisms become deleterious rather beneficial. Chronic increased sympathetic tone causes sustained tachycardia, which increases the oxygen demand of the heart and predisposes to arrhythmias. ACE Merck Veterinary Manual - Summary

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activation results in the formation of angiotensin II, which causes sustained arteriolar and venous constriction and release of aldosterone. Vasoconstriction increases the cardiac afterload, hampering ventricular ejection of blood. Aldosterone release results in sodium and water retention and predisposes to pulmonary edema. Endocardiosis is the most common cardiac disease in veterinary medicine. It most commonly affects the left AV (mitral) valve in horses, dogs, and cats, but the disease is uncommon in cats. In horses, degenerative valve disease often affects the aortic valve and consists of valvular nodules or fibrous bands at the free borders of the valve. In most cases in horses, unlike in dogs, clinical signs are uncommon because significant left ventricular volume overload and dilatation do not occur. Echocardiography is used to confirm the diagnosis and allows visualization of the valvular nodules, fibrous band lesions, and valvular prolapse. Treatment is seldom necessary due to the slow progression of the disease and the ability of the horse to tolerate aortic regurgitation. Endocardiosis occurs primarily in small-breed, older dogs, particularly Miniature Poodles, Shetland Sheepdogs, Lhasa Apsos, Dachshunds, and Cocker Spaniels. Radiographically, left atrial enlargement is the characteristic finding. Other changes include enlargement of the left ventricle and the pulmonary veins. The essentials of treatment are to slow the progression of clinical signs early with vasodilators, to control pulmonary edema when it occurs with vasodilators and diuretics, and to reduce the heart rate and increase contractility later in the course of the disease when vasodilators and diuretics begin to lose their effectiveness. Affected dogs can live for years with clinical signs of degenerative valve disease and proper treatment. Stage 1: A soft (grade 1-2) systolic murmur is present, but there are no clinical signs of heart failure and the left atrium is not enlarged radiographically. No cardiac medications are indicated. The owner should be instructed to avoid feeding any foods or snacks high in sodium. Stage 2: A systolic murmur (grade 2-3) is present, there are no clinical signs, yet the left atrium is enlarged radiographically. Vasodilator therapy (eg, enalapril at 0.4-0.5 mg/kg, s.i.d.) will likely be beneficial. Owners should avoid feeding excessive sodium—a diet specifically formulated for older animals is ideal. Stage 3: A systolic murmur (grade 3-4) is present, and there is cough at night and after activity. There is left atrial enlargement radiographically. Vasodilator therapy should be continued (eg, enalapril, dose increased to 0.4-0.5 mg/kg, b.i.d.). Furosemide should be started at 1 mg/kg, s.i.d. to b.i.d., and the lowest effective dose determined. The animal should be fed a diet specifically formulated for older animals. Stage 4: A loud (grade 4-6) systolic murmur is present. There are signs of heart disease, ie, exercise intolerance and cough, through the day. Radiographically, left atrial enlargement is moderate to marked. The heart rate is increased. Enalapril (0.5 mg/kg, b.i.d.), furosemide (1-2 mg/kg, s.i.d. to b.i.d.), and digoxin (0.22 mg/m2) are indicated. A diet moderately restricted in sodium should be part of the therapy. The Myocardium The myocardium is affected by a variety of disease processes, including primary muscle disorders (eg, dilated or hypertrophic cardiomyopathy), degenerative and inflammatory diseases, neoplasia, and infarction. The myocardium is also sensitive to various toxins, including adriamycin, oleander, and fluoroacetate (1080). Myocarditis occurs in all species and may be caused by viral, bacterial, parasitic, or protozoal infection. Canine parvovirus, encephalomyocarditis virus, and equine infectious anemia are viruses with a propensity to cause myocarditis. Myocardial degeneration occurs in lambs, calves, and foals with white muscle disease and in pigs with mulberry heart disease or hepatosis dietetica. Mineral deficiencies (eg, iron, selenium, and copper) can also result in myocardial degeneration. Dilated Cardiomyopathy: This acquired disease is characterized by the progressive loss of cardiac contractility of unknown cause. Several forms of secondary dilated cardiomyopathy exist (cause known); for example, it can be due to a taurine deficiency in cats or induced by adriamycin or parvovirus. As cardiac contractile function is progressively lost, cardiac output decreases. Increased blood volume and pressure within the chambers causes them to dilate, most dramatically evident in the left atrium and left ventricle. In response to the decreased contractility and cardiac output, the sympathetic nervous system and the renin-angiotensin-aldosterone axis are activated. As in degenerative valve disease, these compensatory mechanisms, although initially beneficial, become deleterious when chronically activated. Constant stimulation of the heart by the sympathetic nervous system causes ventricular arrhythmias and myocyte death, while constant activation of the reninangiotensin-aldosterone axis causes excessive vasoconstriction and retention of sodium and water. In most cases, signs of left-sided congestive heart failure are seen, although signs of right-sided failure (ascites) can develop. Dilated cardiomyopathy is common in large-breed dogs and rare in small-breed dogs (English Cocker Spaniel is an exception). Doberman Pinschers, Great Danes, German Shepherd Dogs, and Labrador Retrievers are particularly at risk.

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The disease is typically seen in middle-aged dogs, with males affected more than females. The incidence in cats has dropped dramatically since the discovery in 1985 that taurine deficiency was responsible for most cases. Signs include exercise intolerance, inappetence, weight loss, cough, weakness, and syncope. Dogs with predominately right-sided failure usually have a more chronic course, with signs including weakness, exercise intolerance, and ascites. A soft systolic murmur, best heard at the left cardiac apex, is usually present. In addition, a third heart sound or gallop is also frequently present, especially in cats. Echocardiography is the ideal test to definitively diagnose dilated cardiomyopathy. There may be electrocardiographic evidence of left atrial enlargement (P mitrale or widened P waves) and left ventricular enlargement (tall and wide R waves). The occurrence of one or more ventricular premature contractions in a presumed healthy Doberman Pinscher is highly suggestive of dilated cardiomyopathy. The objectives of therapy are to control the congestive state (eg, with diuretics), to improve contractility (eg, with digoxin, dobutamine), and to reduce cardiac stress (eg, with vasodilators). Some animals benefit from supplementation with L-carnitine, taurine, or coenzyme Q10. When congestive heart failure is severe, diuretic therapy should be aggressive, eg, furosemide at 4-6 mg/kg, IV, with a repeat dose 4 hr later. Oxygen supplementation should also be provided, either through an oxygen cage or by nasal insufflation. Nitroglycerin ointment is also indicated. A combination dobutamine and sodium nitroprusside infusion is often beneficial. Vasodilator therapy is definitely indicated; enalapril is the preferred drug and should be administered at 0.5 mg/kg, b.i.d. Other ACE inhibitors, such as captopril and benazepril, can be used but are not approved for use in dogs. L-carnitine will help a few dogs, but a dog deficient in L-carnitine cannot be identified without an endomyocardial biopsy. The prognosis is guarded to poor for most dogs. The prognosis is better for dogs exhibiting predominately signs of right-sided failure, with some surviving for 1-2 yr. Hypertrophic Cardiomyopathy: This is the most common cardiomyopathy in cats. It is characterized by left ventricular hypertrophy in the absence of a precipitating cause (such as hypertension or aortic stenosis) and is typically seen in middle-aged cats. Although contractility is not significantly impaired, the hypertrophic ventricular walls lose compliance and resist filling during diastole (diastolic failure). This increases pressure within the left atrium, causing it to dilate; the pressure is then transmitted to the pulmonary veins, causing pulmonary edema. Stasis of blood often occurs in the markedly dilated left atria, predisposing affected cats to aortic thromboembolism. Middle-aged male cats are primarily affected and often develop acute dyspnea, collapse, or hindlimb paresis. Abnormal heart sounds are frequently present and include soft to prominent heart murmurs and gallop rhythms. Increased bronchovesicular sounds and rales are suggestive of pulmonary edema. Pulses may be weak, normal, or absent if thromboembolic disease is present. Radiographically, there is pronounced left atrial enlargement and variable left ventricular enlargement. Evidence of pulmonary edema is frequently present, and pleural effusion is occasionally seen. Echocardiography is the test of choice and allows confirmation of the disease as well as the need for additional therapy (eg, anticoagulant therapy is most beneficial in cats with severe left atrial enlargement). Contractility is usually within normal limits or excessive. A variety of electrocardiographic abnormalities may be present, including atrial premature complexes, ventricular premature complexes, and ventricular tachycardia. Treatment must control pulmonary edema, improve diastolic function, and reduce incidence of systemic thromboembolism. Furosemide and nitroglycerin are indicated when acute pulmonary edema is present. Diltiazem (7.5 mg, t.i.d.), a calcium-channel blocker, improves diastolic function. Vasodilators are occasionally used. Recently, enalapril has been demonstrated to reduce left ventricular hypertrophy and left atrial enlargement in affected cats. Either aspirin (10 mg/kg, every third day) or warfarin (0.2-0.5 mg, daily) is used to reduce the chance of thrombus formation. Myocardial diseases are infrequently reported in horses. Streptococcus is the most common bacterial cause of myocarditis. Salmonella , Clostridium , equine influenza, equine infectious anemia, Borrelia burgdorferi , and strongylosis have also been incriminated. Deficiencies of vitamin E or selenium are known to cause myocardial necrosis. Cardiac toxins include ionophore antibiotics such as monensin and salinomycin, cantharidin (blister beetle toxicosis), Cryptostegia grandiflora (rubber vine poisoning), and Eupatorium rugosum (white snake root poisoning). These diseases cause typical signs of congestive heart failure—exercise intolerance, tachycardia, and tachypnea. In horses, signs of right-sided heart failure are common and include ascites, venous congestion, and jugular pulsations. A neutrophilic leukocytosis and hyperfibrinogenemia are common. Cardiac isoenzymes (creatine kinase and lactate dehydrogenase) are often increased. Treatment should be aimed at improving cardiac contractility, relieving congestion, and reducing vasoconstriction. Digoxin and dobutamine are used most commonly to improve contractility. Furosemide is indicated to control signs of pulmonary edema. Corticosteroids are often used when cardiac isoenzymes are increased and a viral infection is deemed unlikely. Pericardial Effusion When fluid accumulates within the pericardial sac, the pressure within the sac increases and progressively compresses the chambers of the heart. Because the right-sided chambers have thinner walls than the left-sided chambers, they are compressed to a greater degree. Compression of the right-sided chambers has two major consequences: venous return is Merck Veterinary Manual - Summary

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significantly decreased, causing jugular venous distension and ascites, and blood flow to the lungs is significantly decreased, causing hypoxia and tachypnea. Once the pericardial pressure equals or exceeds the cardiac chamber pressures, the condition is referred to as cardiac tamponade. If not treated, cardiac tamponade will result in cardiovascular collapse and death. Pericardial effusion (hydropericardium)is uncommon compared with other acquired cardiovascular diseases but is not rare. It occurs in both small and large animals. There are no breed predilections in cats. Labrador Retrievers and Golden Retrievers are the most commonly affected breeds of dogs. Overall, most cases involve large- and giant-breed dogs (90%), and there is a predilection for males (62%). The severity of clinical signs depends on the rate of pericardial fluid accumulation. Historical features include exercise intolerance, inappetence, listlessness, and abdominal swelling. In horses, there is often a history of respiratory tract infection, fever, anorexia, and depression. Physical examination findings include lethargy, jugular venous distention, muffled heart sounds, and occasionally pericardial friction rubs. Ascites is consistently present in affected dogs. The two most common causes are neoplastic (hemangiosarcoma, heart-based tumor) and idiopathic or benign. Less common causes are infectious (feline infectious peritonitis in cats), trauma, chamber rupture, and secondary to congestive heart failure. Cattle most often develop pericardial effusion secondary to traumatic reticuloperitonitis or lymphoma. In horses, septic and idiopathic are the most common types reported. Results of a complete blood count, serum chemistry profile, and urinalysis are usually within normal limits. A mild anemia, neutrophilic leukocytosis, hyperfibrinogenemia, and hyperproteinemia may occur in horses with septic pericarditis and effusion. Cytologic evaluation of the pericardial fluid can be misleading if the effusion is serosanguinous (95% of all canine effusions). In benign effusions, activated mesothelial cells resemble neoplastic cells, and a false positive may be reported. Radiographic findings include an increase in the size of the cardiac silhouette, which takes on a roundish shape (there is a loss of contour caused by the cardiac chambers). Echocardiography is the ideal test to definitively diagnose pericardial effusion. A tumor can be visualized in many cases of neoplastic effusion, but not all. When cardiac tamponade is present, the walls of the right atrium and right ventricle appear to collapse and flutter. The left-sided chambers are often decreased in size secondary to poor return from the lungs. The height of the R waves is often decreased (4,000 IU/L have a poor prognosis. AST decreases within 3-5 days in horses that improve, and SDH decreases even more rapidly. Total serum bilirubin concentration is generally higher in horses with IAHD than in horses with anorexia. Merck Veterinary Manual - Summary

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Lesions: At necropsy, icterus and varying degrees of ascites are present. Diagnosis: Differential diagnoses include acute pyrrolizidine toxicosis, hepatotoxins, acute infectious hepatitis, acute mycotoxicosis, cerebral disease, and hemolytic disease. Treatment and Prognosis: Supportive therapy and treatment of the hepatic encephalopathy are often successful. Decreases in the SDH and prothrombin time along with improvement in appetite are the best positive predictive indicators of recovery. Horses with fulminant encephalopathy that cannot be easily controlled with sedatives have a poor prognosis, although some recover. For affected horses that do recover, the long-term prognosis is excellent. Prevention: Use of TAT is not without risk. Routine administration of TAT to parturient mares is strongly discouraged. Tyzzer's Disease Tyzzer's disease, due to Clostridium piliforme , causes an acute necrotizing hepatitis, myocarditis, and colitis in foals 842 days old. Etiology: Cholangiohepatitis is a sporadic cause of hepatic failure in horses and in ruminants. It is occasionally associated with cholelithiasis in horses. Bacteremia due to an organism (eg, salmonella) eliminated in the bile or an ascending infection of biliary tract after intestinal disturbance or ileus are thought to be related to the development of cholangiohepatitis. Gramnegative organisms, including Salmonella sp , Escherichia coli , Pseudomonas , and Actinobacillus equuli are frequently isolated from the liver. Clinical Findings: Depending on the severity of infection and virulence of the organism, clinical signs may be acute with severe toxemia, or subacute or chronic. Icterus, photosensitivity, and signs of hepatic encephalopathy are variable. SDH, AST, GGT, bilirubin, and total bile acid concentrations are usually increased. Peripheral WBC counts are variable, depending on the degree of inflammation and endotoxemia present. Lesions: The liver is swollen, soft, and pale. Suppurative foci may be visible beneath the capsule or on cut surface. Lesions in other systems may reflect septicemia and jaundice. Microscopically in acute cases, neutrophils are present in the portal triads and degenerate parenchyma. Purulent exudate is evident in the ducts. In subacute or chronic cholangiohepatitis, the inflammation is more proliferative than exudative. Areas of atrophy, regenerative hyperplasia, and fibrosis may be evident. Diagnosis: Liver biopsy should be performed to confirm the diagnosis and to obtain a liver sample for aerobic and anaerobic culture and sensitivity. Differential diagnoses include other causes of acute to chronic hepatic disease, weight loss, colic, or sepsis. If neurologic signs are present, cerebral diseases must be considered. Treatment: Antimicrobial therapy based on culture and sensitivity results often gives favorable results. Equine Rhinopneumonitis Equine rhinopneumonitis due to equine herpesvirus 1 is a sporadic cause of interstitial pneumonia. Infectious Necrotic Hepatitis (Black disease) Infectious necrotic hepatitis, caused by Clostridium novyi type B, affects primarily sheep but also cattle, horses, and pigs. Hepatic Abscesses The primary etiologic agent of liver abscesses in cattle ( Liver Abscesses In Cattle: Introduction) is Fusobacterium necrophorum . In goats, most abscesses are due to Corynebacterium pseudotuberculosis . Actinomyces pyogenes and Escherichia coli are also common. The liver is particularly susceptible to abscess formation because it receives blood from the hepatic artery, the portal system, and the umbilical vein in the fetus and the neonate. Cholelithiasis, Choledocholithiases, and Hepatolithiasis Etiology and Epidemiology: Cholelithiasis in horses may cause biliary obstruction and concurrent liver disease or may be an incidental finding at postmortem. A solitary or multiple calculi may be present in the common bile duct (choledocholithiasis), intrahepatic bile Merck Veterinary Manual - Summary

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ducts (hepatolithiasis), or bile duct or gallbladder in ruminants (cholelithiasis). The cause of cholelith formation in horses is not known. Ascending biliary tract (cholangiohepatitis) or intestinal bacterial infection resulting in bile stasis and a change in bile composition have been proposed. Choleliths also may form around a foreign body. Clinical Findings: Clinical signs commonly seen in horses with choleliths or cholangiohepatitis include weight loss, abdominal pain, icterus, and intermittent fever. Encephalopathy and photosensitivity are seen less frequently. Laboratory abnormalities include hyperbilirubinemia with increased direct (conjugated) bilirubin, a marked increase in serum GGT activity, and increased serum total bile acid concentration. SDH and AST activities are increased but to a lesser degree. Serum urea nitrogen, glucose, and potassium concentration may be decreased. Function tests indicate reduced hepatic function. Activated partial thromboplastin time and one-stage prothrombin time may be prolonged. Lesions: At necropsy, the liver may be enlarged or shrunken. The liver is red to green-brown and firmer than normal. Hepatic ducts and the common bile duct are dilated and may contain one or more calculi. Chronic Active Hepatitis Chronic active hepatitis describes any progressive inflammatory process within the liver. It is a histopathologic diagnosis in which there is evidence of sustained, aggressive, chronic liver disease. The histologic diagnosis is usually cholangiohepatitis. Etiology: The exact etiology is not known. Infectious, immune-mediated, or toxic processes are thought to be involved. The early stages are associated with inflammation of the bile ducts and portal areas of the liver. Extension of bacterial infection through the bile duct or portal venous drainage may be responsible for the lesions in animals with suppurative cholangiohepatitis. When lymphocytes and plasma cells are predominant in the cellular infiltrate, an immune-mediated process is more likely. Clinical Findings: The predominant clinical signs are weight loss, anorexia, and depression. GGT and AP are moderately increased, as are SDH and glutamate dehydrogenase, which indicates ongoing hepatocyte damage. Serum total protein is either increased or normal. Globulins are usually increased. Serum total bile acid concentration is increased, and BSP clearance prolonged. Cholestasis may cause hyperbilirubinemia with >25% of total bilirubin being direct. With diminishing hepatic function, serum glucose and coagulation factors decrease, and one-stage prothrombin time and activated partial thromboplastin time become prolonged. There may be a neutrophilia or neutropenia with a left shift if endotoxemia occurs. As the disease becomes chronic, a nonregenerative anemia and hyperfibrinogenemia can develop. Anorexia can lead to hypokalemia. Ultrasound examination generally reveals increased echogenicity in the liver indicative of hepatic fibrosis. The liver may be smaller than normal. Diagnosis: Histologic examination of a liver biopsy is needed for a definitive diagnosis. Treatment: Supportive care should be provided, including fluid therapy with potassium chloride, glucose, and vitamin supplementation; dietary management (a low-protein, high branched-chain amino acid, high-carbohydrate diet); and prevention of exposure to the sun if photodermatitis is present. The risk of inducing laminitis or abortion in pregnant animals with corticosteroids must be discussed with the owner before initiating therapy. Alternatively, an antifibrotic agent, colchicine (0.03 mg/kg/day, PO) has been recommended, but its efficacy in hepatic failure and safety in pregnant animals is unproved. Possible adverse reactions to colchicine in horses include laminitis and diarrhea. Hyperlipemia in Horses and Donkeys Epidemiology and Pathogenesis: Low feed quality or decrease in feed intake, particularly during a period of high-energy requirement (eg, pregnancy, systemic disease), may result in hyperlipemia syndrome. Hyperlipemia occurs most commonly in ponies, miniature horses, and donkeys, and less frequently in standard-size adult horses. Pathogenesis of hyperlipemia is complex, with a negative energy balance triggering excessive mobilization of fatty acids from adipose tissue leading to increased hepatic triglyceride synthesis and secretion of very low density lipoproteins, concomitant hypertriglyceridemia, and fatty infiltration of the liver. The biochemical etiology of hyperlipemia is overproduction of triglyceride, rather than failure of triglyceride catabolism. Onset of disease is associated with stress, decreased feed intake, and an insulin resistance resulting in mobilization of fat. In ponies, hyperlipemia is usually a primary disease process associated with obesity, pregnancy, lactation, stress, or transportation. Hyperlipemia may occur secondary to any systemic disease that results in anorexia and a negative energy balance. Secondary hyperlipemia is more common than primary hyperlipemia in miniature breeds. Hyperlipemia secondary to a systemic disease can occur in horses of any age and in any condition. Females, stressed, and obese donkeys are at Merck Veterinary Manual - Summary

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highest risk of developing hyperlipemia regardless of pregnancy status. Hyperlipemia is most commonly seen in the winter and spring. Clinical Findings: Signs are nonspecific and include depression, weakness, inappetence, adipsia, and diarrhea. Often, there is a history of prolonged anorexia, rapid weight loss, and previous obesity. Affected animals are hypertriglyceridemic with grossly lipemic plasma. Healthy donkeys have higher plasma triglyceride concentrations than do other equids. Hypoglycemia is a common finding in ponies but not in miniature horses with hyperlipemia. Activated partial thromboplastin time and one-stage prothromin time may be prolonged. AST and SDH may be normal or increased. Increased creatinine, isosthenuria, and metabolic acidosis may occur secondary to renal disease. Alpacas and llamas in late stages of gestation may develop hyperlipemia and ketonuria. Lesions: Microscopically, there is varying degrees of fat deposition within the hepatocytes and epithelium of the bile ducts. Diagnosis: Clinical diagnosis is often based on the signalment, history, clinical signs, and gross observation of a white to yellow discoloration of the plasma. Plasma or serum triglyceride levels >500 mg/dL confirm the diagnosis. Treatment: Correction of the underlying disease, IV fluids, and nutritional support are the most essential factors in treatment of hyperlipemia. Frequent feedings of a high-carbohydrate, low-fat diet is preferred. In animals with inadequate oral intake, supplemental tube feeding is necessary. Exogenous insulin administration is recommended for treatment of iatrogenic hyperglycemia and hyperlipemia. Insulin decreases mobilization of peripheral adipose tissue by stimulating lipoprotein lipase activity and by inhibiting adipocyte hormone-sensitive lipase activity. The appropriate dose of insulin to be used in the horse has not been well established. Anecdotal recommendations for use of lente (0.15-0.25 IU/kg, b.i.d., IM or SC) and ultralente (0.5 IU/kg/day, IM or SC) insulin have been made, but response to therapy must be closely monitored and insulin dose adjusted accordingly. Heparin is used in treatment of hyperlipemia because it promotes peripheral utilization of triglycerides and enhances lipogenesis via stimulation of lipoprotein lipase activity. Heparin administration may potentiate bleeding complications and is contraindicated in animals with coagulopathies from liver dysfunction. Prognosis: Death from hyperlipemia is rare in miniature breeds. Prognosis is often poor in ponies and standard-size horses. Hepatic Neoplasia Primary hepatic tumors are uncommon in horses and ruminants. They include hepatocellular carcinoma, cholangiocarcinoma, and rarely lymphomas or other neoplasias. Hepatic carcinomas arise from hepatocytes, bile ducts, or metastasis. Hepatocellular carcinomas generally are found in yearlings to young adult horses and have also been reported in llamas and goats. Cholangiocarcinoma is primarily found in middle-aged or older horses. Adenomas or adenocarcinomas of the liver have been reported in cattle. Lymphosarcoma is the most common neoplasia of the hematopoietic system in horses. As many as 37% of horses with lymphosarcoma have neoplastic involvement of the spleen, and 41% have neoplastic involvement of the liver. Clinical Findings: Liver hepatocellular and biliary enzymes may be increased with hepatic carcinoma or cholangiocarcinoma. Serum GGT activity in affected horses is usually very high. Clinical manifestations of lymphosarcoma in horses are variable. Early in the disease, nonspecific signs such as weight loss, anorexia, and lethargy are seen. Lymphoma occasionally may diffusely infiltrate the liver and produce signs of hepatic failure, jaundice, and severe depression. Diagnosis: The presence and character of the hepatic neoplasia can be confirmed by liver biopsy and microscopical examination of the tissue. Atypical lymphocytes or lymphoblasts may be seen in peritoneal fluids and peripheral blood of some affected animals. Potomac Horse Fever (Equine ehrlichial colitis, Equine monocytic ehrlichiosis) The disease has not been recorded outside North America. It occurs sporadically, frequently with only one horse on a farm being affected. Epidemiologic studies have shown a seasonal nature of the disease, with a higher incidence in summer and autumn. Because the disease can be transmitted by blood inoculation, an arthropod vector for E risticii has been suspected but has not yet been identified. Most rickettsiae are transmitted by ticks, fleas, or lice. Clinical Findings: Merck Veterinary Manual - Summary

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Clinical signs include lethargy, anorexia, fever, mucous membrane injection, ileus, colic, diarrhea, and laminitis. Colitis is present in all cases but does not result in diarrhea or colic in all horses. Signs of ileus are most consistent of all clinical signs. Diarrhea develops in 140 beats/min, or if the R wave occurs close to the T wave (a phenomenon that predisposes to ventricular fibrillation). If predisposing factors have been addressed and persistent ventricular arrhythmias warrant therapy, 2% lidocaine hydrochloride without epinephrine (2-4 mg/kg, slowly IV) is given and repeated twice during a 30-min period if necessary. Continuous IV infusion (30-80 µg/kg/min) may be indicated to control arrhythmias. Cardiac arrhythmias associated with GDV are often difficult to control. Life-threatening arrhythmias may respond to 20% magnesium sulfate Dogs with a tendency to develop dilatation and volvulus should be fed smaller meals more frequently over the course of the day. Excessive exercise should be avoided to decrease the likelihood of volvulus, and consumption of large volumes of water after exercise should be avoided to limit gastric distention. Gastrointestinal Obstruction: Introduction Gastric outflow obstruction can result from neoplasia, foreign bodies, polyps, ulcers, and gastric mucosal hypertrophy. Pyloric stenosis secondary to chronic hypertrophic gastropathy is the most common cause of gastric outflow obstruction. It occurs as a congenital lesion and is most often reported in brachycephalic breeds; it also occurs as an acquired lesion in older dogs. In dogs, there is a history of chronic intermittent vomiting and gastric distention. It tends to affect middle-aged to older dogs. Benign tumors include polyps and leiomyomas. Adenocarcinoma is the most common malignant form of tumor in dogs; metastasis is common, and the prognosis is poor. Therapy for gastric outflow obstruction is generally surgical. Response of chronic hypertrophic pyloric gastropathy to surgery is good to excellent. Intestinal obstruction may be partial or complete and may be caused by foreign bodies, intussusception, gastric dilation-volvulus, incarceration, and neoplasia. Pathophysiology: Intussusception tends to occur when one segment of the intestine is hypermotile. The most common area for this to occur is the ileocecocolic junction, where the smaller segment of ileum may slide into the larger lumen of the colon. Distention with gas and fluid occurs proximal to the obstruction. Strangulation or incarceration of bowel occurs with entrapment of intestinal loops in hernias or mesentery. Venous return is impaired although arterial supply remains intact, leading to venous congestion, anoxia, and, necrosis. Loss of blood into the intestinal lumen and peritoneal cavity and the subsequent emigration of bacteria and toxins from the devitalized tissue ensues. The most common toxin-producing bacteria are Escherichia coli and clostridia. Clinical Findings: Upper or duodenal obstruction tends to present as frequent vomiting. In general, the closer the obstruction to the pylorus, the more severe the vomiting. Obstruction of the lower small intestine (eg, distal jejunum and ileum) is infrequently associated with vomiting. Intussusception is more common in young dogs (< 6-8 mo old). Diagnosis:

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Linear foreign bodies most often lodge at the base of the tongue in cats and at the level of the pylorus in dogs. Careful abdominal palpation examining for evidence of pain (ruptured bowel, peritonitis), organomegaly, thickened bowel loops (intussusception), and tympany (dilation-volvulus), and a rectal examination examining for evidence of dietary indiscretion or blood (suggestive of strangulation) are important components of the physical examination. Intussusception can be difficult to identify on abdominal palpation because the affected segments of intestine are not always turgid. Bowel loops that are incarcerated often become distended and painful. The presence of free abdominal gas on survey radiographs is associated with high mortality rates. Barium contrast radiographs are best for demonstration of ileocolic intussusception. In animals that are systemically ill, a complete blood count, biochemical profile including electrolytes, and a urinalysis should be completed before therapy is initiated. Strangulation of gut causes a leukocytosis with a left shift early in the course of disease or leukopenia later and a low PCV. Initially, fluid lost into the intestinal lumen is isotonic. With time, there is an increased secretion of sodium, potassium, and albumin into the intestine. The additional loss of bicarbonate-rich secretions contributes to metabolic acidosis. Hypoproteinemia, with or without iron-deficiency anemia due to GI blood loss, is common in chronic intussusception. Treatment: Animals that are systemically ill benefit from IV fluid therapy (eg, lactated Ringer's or normal saline). Large-intestinal surgery tends to be associated with longer surgery and recovery times. Surgery and multiple enterotomies are necessary in most cats for the removal of linear foreign objects, yet many recover well. Peritonitis and death associated with linear foreign objects is much more common in dogs than in cats. Gastrointestinal Ulcers In Small Animals: Introduction Etiology and Pathophysiology: GI ulcers result from a breakdown of the normal gastric mucosal barrier or from an increase in hydrochloric acid or pepsin production. Prostaglandins maintain integrity of gastric mucosa by inhibiting gastric acid secretion, enhancing gastric bicarbonate production, preserving mucosal blood flow, stimulating epithelial cell turnover, and promoting the secretion of gastric mucus with an increased protein content. Injury to the mucosal barrier results in “back diffusion” of luminal acid into the mucosa, which initiates a series of events that results in cellular damage. The small amount of acid that normally diffuses into the mucosa is rapidly cleared by mucosal blood flow. Mast cells in the submucosa and lamina propria degranulate upon contact with acid, releasing histamine. Histamine stimulates parietal cell secretion of hydrochloric acid and promotes cellular injury. It is this back diffusion of hydrochloric acid that is the principal factor eliciting mucosal erosion and ulceration. Conditions predisposing to increased acid production or mucosal damage facilitates ulcer production. Acid also damages local blood vessels and nerves. Potential causes of GI ulceration include the following: 1) drugs—nonsteroidal anti-inflammatory drugs (including aspirin, phenylbutazone, ibuprofen, indomethacin, flunixin meglumine, naproxen, and piroxicam) and corticosteroids; 2) neoplasia—lymphosarcoma, adenocarcinoma, gastrinoma (Zollinger-Ellison syndrome), and mastocytosis; 3) systemic disease—renal or hepatic failure, hypovolemic shock, hypoadrenocorticism, sepsis, spinal injury, and pancreatitis; 4) other causes— Helicobacter spp , pyloric outlet obstruction, inflammatory bowel disease, chronic gastritis. Aspirin, a nonsteroidal anti-inflammatory drug (NSAID), directly injures gastric epithelial cells and impairs prostaglandin E production. Standard formulations of buffered aspirin do not provide sufficient buffering to neutralize gastric acid or prevent mucosal injury. Gastrinoma and mastocytosis cause ulcer formation by increasing acid production. Renal failure results in the retention of uremic toxins and gastrin that damage the gastric mucosa and blood vessels of the gastric wall and result in increased acid production. The exact mechanism(s) by which liver failure favors ulcer production is unknown but may include reduced mucosal blood flow, increased serum levels of gastrin and histamine, and contribution to a loss of the normal mucosal barrier. Hypotension, hypovolemic shock, and sepsis impair normal gastric microcirculation leading to ischemia and cell death. Spinal cord lesions may affect autonomic nervous control of blood vessels to the gut causing vasodilation, vascular stasis, and ischemia. Dogs with spinal cord lesions undergoing surgery and receiving corticosteroids are prone to hemorrhagic gastroenteritis and perforating gastric ulcers. Clinical Findings: Animals with gastric ulceration may be asymptomatic or have a history that includes vomiting, sometimes with frank or digested blood, and abdominal discomfort that may appear less severe after a meal. Diagnosis: Diagnostic work on animals with a history of vomiting, abdominal discomfort, anorexia, or weight loss of unknown etiology should begin with a complete blood count, biochemical profile, trypsin-like immunoreactivity analysis, urinalysis, and fecal parasite evaluation. In cases in which the etiology remains obscure or in those with apparent GI pathology, gastroduodenoscopy and biopsy should be done. Treatment and Control: Merck Veterinary Manual - Summary

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The primary goal of ulcer management is to determine and eliminate or control the cause of the ulceration and provide supportive care. Gastric acid production is stimulated by histamine (most potent), gastrin, and acetylcholine. H2-blocking agents reversibly bind H2-receptors and impede endogenous histamine occupation of the receptor. H2-blocking agents include cimetidine, ranitidine, and famotidine. Cimetidine (10 mg/kg, t.i.d., PO, IM, or IV) inhibits gastric acid secretion for 3-4 hr and requires dosing 3-4 times daily. Although no drug is more efficacious than the other in promoting ulcer healing, ranitidine (dogs: 2 mg/kg, t.i.d., PO or IV; cats: 2.5 mg/kg, b.i.d., IV, or 3.5 mg/kg, b.i.d., PO) is 4-10 times more potent and famotidine (0.5 mg/kg, every 12-24 hr, PO, IM, IV, or SC) 20-40 times more potent than cimetidine. Omeprazole (0.7 mg/kg, s.i.d., PO) acts by inhibiting the hydrogen-potassium ATPase responsible for hydrogen ion production in the parietal cell. It is 2-10 times more potent than cimetidine in decreasing intragastric acidity. In a study in dogs, it was demonstrated that once daily administration of omeprazole was as effective as cimetidine given three times daily in lessening aspirin-induced gastritis. Cytoprotective agents include antacids and sucralfate. Antacids are as effective as other antiulcerative agents but require more frequent dosing (eg, aluminum hydroxide in dogs is given at ½-1 tablet, q.i.d., and in cats at ¼tablet, q.i.d.). One antacid tablet containing aluminum hydroxide given four times daily is as effective as higher doses of liquid antacids and cimetidine in promoting ulcer healing. Sucralfate (dogs: 0.5-1 g, every 8-12 hr, PO; cats: 0.25 g, every 8-12 hr, PO) forms a complex with proteinaceous exudates that adheres to the ulcer, providing a protective barrier to the penetration of acid. Misoprostol (dogs: 2-5 µg/kg, t.i.d., PO) is a synthetic prostaglandin E1 analog. The drug inhibits gastric acid production and has a cytoprotective effect. It is effective in the prevention of NSAID-induced GI ulceration, whereas cimetidine and sucralfate have a therapeutic effect only if NSAID are discontinued. In spite of its efficacy, misoprostol has not been reported to decrease the frequency of GI pain associated with NSAID use. It is as effective as other antiulcerative drugs in treating GI ulcers in cases other than those associated with NSAID use, but in these cases, it offers no clear advantage over these other products. Hemorrhagic Gastroenteritis: Introduction Hemorrhagic gastroenteritis (HGE) is characterized by an acute onset of bloody diarrhea in formerly healthy dogs. Young, toy and miniature breeds of dogs appear predisposed. Mortality is high in untreated dogs. Etiology and Pathophysiology: The etiology is unknown. King Charles Spaniels, Shelties, Pekingese, Yorkshire Terriers, Poodles, and Schnauzers may be over-represented; hyperactivity and stress are possible contributing factors. Although no definitive cause has been found, a marked increase in vascular and mucosal permeability is likely. Red blood cells, plasma, and fluid leak into the bowel lumen. Inflammation and necrosis are rarely seen. The increase in bowel permeability may represent a type I hypersensitivity reaction. Inciting factors may include food allergens, bacterial products, or intestinal parasites. Splenic contraction and the loss of plasma protein into the bowel contributes to the increased PCV and the maintenance of a low or normal serum total protein. Clinical Findings: The disease is often seen in dogs 2-4 yr old and is characterized by an acute onset of vomiting and bloody diarrhea, anorexia, and depression. Dogs are not clinically dehydrated, but unless fluid support is initiated, hypovolemic shock may develop. The disease is not contagious and may occur without obvious changes in diet, environment, or daily routine; the history is unremarkable. Diagnosis: Diagnosis is based on the clinical sign of acute, bloody diarrhea accompanied by an increased PCV, which is often >60%. Findings on physical examination and biochemical profile tend to be normal. Other causes of GI bleeding that should be considered include parvovirus, coronavirus, Campylobacter sp , Salmonella sp , Clostridium sp , Escherichia coli , and leptospirosis, as well as whipworms, hookworms, coccidiosis, and giardiasis. Coagulopathies (including warfarin toxicity and thrombocytopenia), GI neoplasia, ulceration, colitis, and hypoadrenocorticism are other potential causes of GI bleeding. Treatment: Most dogs respond to supportive treatment, including fluid therapy (eg, lactated Ringer's) and antibiotics (eg, ampicillin (20 mg/kg, t.i.d., IV) and gentamicin (2.2 mg/kg, t.i.d., SC). Potassium chloride should be added to the IV fluids. Because of the possibility that food sensitivity may be an inciting factor, the protein source chosen should be one unfamiliar to the dog, eg, cottage cheese, lamb, or tofu, mixed with rice. Inflammatory Bowel Disease: Introduction Idiopathic inflammatory bowel disease (IBD) constitutes a group of GI diseases characterized by persistent clinical signs and by histologic evidence of inflammatory cell infiltrate of unknown etiology. Etiology and Pathophysiology: The etiology of IBD is unknown. German Shepherd Dogs may be predisposed to lymphocytic-plasmacytic enteritis. Merck Veterinary Manual - Summary

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Current evidence supports the likely involvement of hypersensitivity reactions to antigens (eg, food, bacteria, mucus, epithelial cells) in the intestinal lumen or mucosa. More than one type of hypersensitivity reaction is involved in IBD; for example, type I hypersensitivity is involved in eosinophilic gastroenteritis, whereas type IV hypersensitivity is likely involved in granulomatous enteritis. The hypersensitivity reaction incites the involvement of inflammatory cells that results in mucosal inflammation. Inflammation impairs the mucosal barrier, facilitating increased intestinal permeability to additional antigens. Persistent inflammation results in fibrosis. Clinical Findings: There is no apparent age, sex, or breed predisposition associated with IBD. However, it may be more common in German Shepherd Dogs, Yorkshire Terriers, Cocker Spaniels, and purebred cats. The mean age reported for the development of clinical disease in dogs is 6.3 yr and in cats is 6.9 yr, but IBD has been documented in dogs 50% of cats with lymphocytic-plasmacytic enterocolitis; 50% of affected cats are thin or cachexic in appearance. Diagnosis requires intestinal mucosal biopsy. Histologic infiltrates with eosinophils may be found in some dogs and cats with absolute eosinophilia. Hyperproteinemia due to increases in serum globulin or hypoalbuminemia due to reduced dietary intake and malabsorption or increased loss via the GI tract, may be seen. Increases in serum amylase as a consequence of inflammation of the bowel is also reported. Hypokalemia secondary to anorexia and potassium loss from vomiting and diarrhea, as well as low serum levels of folate and cobalamin are also documented. Additionally, mild increases in serum levels of liver enzymes can be expected. Treatment and Control: The goals of therapy are to reduce diarrhea, promote weight gain, and decrease intestinal inflammation. If Corticosteroids, azathioprine, azulfidine, tylosin, and metronidazole are among the drugs most often used in the management of IBD. Dietary modification generally involves feeding a hypoallergenic or elimination diet, ie, feeding a source of protein that the animal has not been previously exposed to such as homemade diets of lamb and rice or venison and rice. This diet should be the sole source of food for a minimum of 4-6 wk, and no treats of any kind should be fed. Dietary changes alone are rarely effective in controlling clinical signs in cats. Dogs with large-intestinal diarrhea may benefit from diets high in insoluble fiber content. Supplementation of dietary fiber alone is rarely effective in cases with severe inflammatory cell infiltrate. Corticosteroids may be useful for small- as well as large-intestinal disease. When combination therapy is indicated in cats, prednisone is often combined with metronidazole. Azathioprine is commonly used in the management of IBD in dogs and cats. Cats are especially prone to bone marrow toxicity, and the dosage is decreased accordingly. Azulfidine is used in the management of colitis in dogs. In the colon, azulfidine is split to release 5-aminosalicylic acid, which exerts anti-inflammatory activity in the mucosa. The principal adverse effects noted in dogs are keratoconjunctivitis sicca and vasculitis. Exocrine Pancreatic Insufficiency Exocrine pancretic insufficiency (EPI) is a malnutrition disorder caused by a deficiency of pancreatic digestive enzymes. It is much more common in dogs than in cats, and in dogs, it is most common in German Shepherd Dogs. EPI is usually caused by an idiopathic atrophy of the acinar cells that contain zymogen but can also be caused by recurrent pancreatitis and the associated loss of acinar cells. It rarely occurs with pancreatic adenocarcinoma because the malignancy will often cause death long before most of the exocrine pancreatic cells are destroyed. EPI is rare in cats, in which the signs are similar to those in dogs. Clinical Findings and Diagnosis: Classic signs include polyphagia, weight loss despite a ravenous appetite, and frequent passage of large volumes of feces. Pica and coprophagia can also be seen. The feces range from diarrheal to semiformed and may be foul smelling; they are brown to yellow and have a greasy texture (as may the perineum) due to steatorrhea. Animals with EPI are typically thin and have dull, dry hair coats, which reflect their malnourished condition. Polydipsia and polyuria can be seen if diabetes mellitus is also present. In cats, the neck should be palpated thoroughly for thyroid gland enlargements, which will support a diagnosis of hyperthyroidism.

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The hemogram is normal or shows a mild normochromic, normocytic anemia due to malnutrition. Hypoproteinemia can occur as a result of faulty digestion and impaired assimilation of ingested proteins. Hyperglycemia can occur if 90% of the pancreas has been destroyed by earlier pancreatitis. Diagnosis: Examination of the feces for the presence of fat or carbohydrate, and trypsin activity (film digestion) are empirical tests and frequently yield inaccurate results. Treatment and Prognosis: Once EPI is diagnosed, treatment is rather simple. A commercial pancreatic enzyme product (the powdered form is preferred over tablets) should be thoroughly mixed in a moist, nutritionally balanced ration (1 tsp/0.5 kg of food) at each feeding. Some dogs that have concurrent intestinal bacterial overgrowth require antimicrobial treatment (tetracycline, 15 mg/kg, t.i.d.) to enhance the effectiveness of treatment. Increased amounts of food should be provided until normal body weight is reached. The prognosis for most animals is excellent with appropriate therapy. Hepatic Disease In Small Animals: Introduction Clinical Findings and Pathophysiology: Hepatic encephalopathy is seen in a number of liver diseases. Clinical signs suggestive of hepatic encephalopathy include circling, head pressing, aimless wandering, weakness, ataxia, blindness, ptyalism, aggression, dementia, seizures, and coma. The failure of the liver to clear several neurotoxins is a major contributing factor to hepatic encephalopathy. Ammonia, γ-aminobutyric acid (GABA), aromatic amino acids, mercaptans, and short chain fatty acids are a few of the neurotoxins implicated. Colonic bacteria metabolize proteins and urea into un-ionized ammonia , which is readily absorbed into the portal circulation. In animals with normal liver function, most of the ammonia is removed by hepatocytes and converted into amino acids or urea. When the liver is dysfunctional or, in the case of portosystemic shunts, in which the portal blood bypasses the liver, blood ammonia levels remain high. Ammonia levels are also increased with GI bleeding, which can be seen with liver disease due to ulceration or coagulation abnormalities. Other factors that can increase blood ammonia levels include azotemia, alkalosis, and, in cats, anorexia. However, ammonia concentrations are not directly correlated with the degree of hepatic encephalopathy. Levels of GABA in the CNS are also increased in hepatic disease by two means. Ammonia is a substrate for GABA; therefore, increased ammonia levels result in increased GABA levels in the CNS. Also, GABA is produced by intestinal bacteria, and clearance is decreased in hepatic dysfunction, resulting in increased CNS uptake. Because GABA receptors are complexed with receptors for diazepam and barbiturates, use of these drugs can exacerbate signs of hepatic encephalopathy. Aromatic amino acids are also used in the brain to synthesize inhibitory neurotransmitters. An increase in aromatic amino acids is due to decreased hepatic catabolism of these compounds. Increased uptake of aromatic amino acids contributes to clinical signs of hepatic encephalopathy. Mercaptans are produced by intestinal bacteria as a result of metabolism of sulfur-containing amino acids. As with ammonia, mercaptan levels increase with liver disease because of decreased clearance. Mercaptan metabolism by the liver is also reduced when ammonia levels and short-chain fatty acid levels are increased. The neurotoxic effects of mercaptans contribute to hepatic encephalopathy. Short-chain fatty acids have a barbiturate-like effect on the brain. Decreased liver catabolism results in increased blood levels, which have not only a direct effect on the CNS but also an indirect effect by interfering with hepatic metabolism of ammonia and mercaptans. Ascites is seen more often in dogs with liver disease than in cats. Portal hypertension can be due to intrahepatic obstruction, obstruction of the portal veins, increased volume of portal blood flow, obstruction or kinking of the caudal vena cava, or secondary to right heart failure. Causes of intrahepatic obstruction include inflammation, fibrosis, necrosis, regenerative nodules, or neoplastic masses. Ascites can be exacerbated by hypoalbuminemia. Cytologic evaluation of the ascitic fluid is consistent with a modified transudate. Laboratory Analyses: Severe or acute anemia can inhibit liver function because of hypoxia. Leukocytosis can be seen with inflammatory diseases; leukopenia with sepsis. Decreased GI absorption of vitamin K because of decreased bile production can also lead to coagulopathies. Liver enzyme activity is often an indicator of liver dysfunction, although levels may be normal in certain situations, eg, end-stage liver disease. Changes in cell permeability, hepatocellular degeneration or necrosis, and inflammation can cause release of ALT and AST from hepatocytes and subsequent increase of serum values. AST is a less reliable indicator of liver disease than ALT for several reasons. First, AST is also present in heart, skeletal muscle, kidney, brain and plasma; therefore, an increase can indicate an extrahepatic disease. ALT levels within hepatocytes are much greater than AST levels. Finally, AST values may return to normal before ALT values as disease resolves. However, in certain diseases in cats and in metastatic disease in dogs, AST may be a more sensitive indicator of hepatobiliary disease as well as a prognostic indicator. Merck Veterinary Manual - Summary

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ALT levels rise rapidly after hepatobiliary necrosis or inflammation. Extrahepatic biliary obstruction results in a more gradual increase in ALT. Drugs that induce microsomal enzymes, including anticonvulsants and prednisone, may cause an increase in ALT in dogs, although levels usually are lower than those associated with disease. Decrease in ALT levels with acute disease is usually a good prognostic indicator. However, in chronic disease, a decrease in ALT may be due to recovery or to a severe decrease in hepatocyte population, as seen with end-stage disease. Alkaline phosphatase (AP) is a membrane-bound enzyme found in a number of different tissues. In dogs, significant increases in AP activity can be attributed to bone isoenzyme (young animals, panosteitis, bone tumors, and secondary renal hyperparathyroidism), corticosteroid isoenzyme (excessive corticosteroids, either exogenous or endogenous), or liver isoenzymes. With acute hepatocellular necrosis, AP values lag behind an increase in ALT values; they are usually mildly to moderately increased and can return to normal in 2-3 wk. Highest values are noted with cholestatic disease, extrahepatic bile duct obstruction, hepatic neoplasia, and enzyme induction. Increased AP levels can also be caused by hepatic inflammation and systemic infection or inflammation and have been reported as a possible paraneoplastic syndrome seen with mammary adenocarcinoma. Minor increases in AP activity can be seen in numerous diseases, including hypothyroidism, hyperthyroidism, diabetes mellitus, pancreatitis, anoxia, hyperthermia, thromboembolism, hypotension, septicemia, and endotoxemia. Anticonvulsants, glucocorticoids, thiacetarsamides, and ketoconazole can also cause an increase in AP. AP increases in cats are liver-specific and tend to be less severe than in dogs. In cats, AP is primarily derived from the liver and has a significantly shorter half-life than in dogs, and there is no corticosteroid isoenzyme. Therefore, mild increases of AP in cats are significant indicators of liver disease. (Placental enzymes may cause slight increases late in pregnancy.) AP in cats is rarely affected by anticonvulsants or glucocorticoids but can be increased in diabetes mellitus, hyperthyroidism, and pancreatitis. Highest levels are seen in hepatic lipidosis. Increase of AP precedes increase of bilirubin in both dogs and cats with cholestasis. AP is a sensitive but not specific indicator of hepatobiliary disease in dogs; in cats, AP is highly specific but not as sensitive. Simultaneous evaluation of γglutamyltransferase increases the specificity of AP as an indicator of liver disease in dogs and the sensitivity in cats. The liver is the major contributor to serum γ-glutamyltransferase (GGT), which increases with intrahepatic and extrahepatic cholestasis and pancreatitis. The kidney and pancreas also have high tissue levels of GGT but do not contribute to serum values. In dogs, GGT activity can be stimulated by glucocorticoids and anticonvulsants. In cats, GGT is more sensitive and less specific than AP, and it can be increased to a greater degree than AP in certain diseases, including cirrhosis, bile duct obstruction, and intrahepatic cholestasis. Little to no increase in GGT levels is seen with acute hepatic necrosis. Albumin levels may be decreased due to decreased synthesis, increased volume of distribution (ascites), or leakage into the ascitic fluid. Hypoalbuminemia can also cause ascites. Decreased albumin level is usually an indicator of severe or chronic liver disease. Glomerular disease or protein-losing enteropathy must be ruled out as a cause for hypoalbuminemia. Serum globulins that are synthesized in the liver can be decreased in liver disease. However, immunoglobulin levels are usually increased in liver disease due to inflammation or immune stimulation. Bilirubin levels can be increased due to prehepatic causes (such as hemolysis) or to intrahepatic or extrahepatic cholestasis. Extrahepatic cholestasis usually results in higher levels of hyperbilirubinemia than intrahepatic causes. AP values will increase before serum bilirubin values. In dogs, bilirubinuria will be detected before bilirubinemia because the renal threshold for bilirubin is very low. Cats have a much higher renal threshold, and bilirubinemia is detected before bilirubinuria. Icteric cats with anemia should always be tested for hemobartonellosis. Recently, a form of bilirubin tightly bound to albumin, referred to as biliprotein or delta bilirubin, has been identified. Delta bilirubin is not excreted in the urine and remains in circulation for a prolonged time. When a significant amount of bilirubin is in the form of delta bilirubin, animals can be icteric without bilirubinuria and can remain icteric for several weeks to months after the cholestatic disease has resolved. BUN can be decreased in animals with liver disease because of decreased conversion of ammonia to urea. Anorexia or a low-protein diet can also cause lower BUN values. Hypocholesterolemia can be seen in portosystemic shunts or end-stage liver disease. Bile acid levels are used to evaluate liver function. Because icterus is an indicator of defective bile metabolism, measurement of serum bile acids is not necessary in icteric animals. Bile acids may be increased in certain nonhepatic diseases, including inflammatory bowel disease, hyperadrenocorticism, and pancreatitis. Two other methods of evaluating liver function are a fasting ammonia level, followed by (if fasting levels are normal) an ammonia tolerance test. A complete coagulation profile should be done before attempting to collect any biopsy samples. Treatment and Management: Unfortunately, most acute and chronic forms of liver disease have no specific therapy, and treatment relies on supportive care and management of complications. Hepatic Encephalopathy: Treatment of acute hepatic encephalopathy is aimed at providing supportive therapy and rapidly reducing the neurotoxins being produced by the colon. Affected animals are usually comatose or semicomatose. Cleansing enemas of Merck Veterinary Manual - Summary

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warm soapy water, followed by retention enemas of either lactulose (three parts lactulose to seven parts water at 20 mL/kg), 10% povidone-iodine solution (20 mL/kg), or neomycin (22 mg/kg) should be given every 6 hr until the animal is stable. Lactulose is a nonabsorbable disaccharide that interacts with bacterial flora and decreases encephalopathic toxin production. The sugars are not absorbed but are fermented in the colon to organic acids; this lowers colonic pH and traps ammonia in the ionized form, which prevents absorption. Disaccharides also provide an alternate substrate for bacterial metabolism and, therefore, decrease the amount of ammonia produced. In addition, disaccharides are osmotic cathartics and decrease noxious substances and ammonia-producing bacteria by purging. Neomycin and povidone-iodine directly alter the colonic bacterial population, decreasing the population of ammonia-producing bacteria. Protein-restricted diets should be fed. The clinical signs of hepatic encephalopathy can be exacerbated by GI bleeding, infection, glucocorticoid use (resulting in increased catabolism of tissue protein), neoplasia, fever, azotemia or dehydration (due to increased urea production), constipation (causing increased generation of colonic neurotoxins), metabolic alkalosis (favoring both production of ammonia by the kidneys and uptake of urea by the blood-brain barrier), and use of diazepam and barbiturates (synergetic neuroinhibitors.) Ascites: The first step in control of ascites is dietary sodium restriction. However, sodium-restricted diets alone are often not sufficient, and diuretics are recommended. Diuretic therapy should be directed at slowly reducing ascites without causing dehydration, metabolic alkalosis, and hypokalemia. Spironolactone (1-3 mg/kg, PO, b.i.d.) is recommended initially; if spironolactone is not effective, furosemide (1-2 mg/kg, PO, b.i.d.) can be added. If the ascites is causing respiratory compromise, then abdominocentesis is recommended to temporarily reduce fluid buildup. Possible complications to removing large volumes of fluid by abdominocentesis include hypotension and hypoalbuminemia. Coagulation Abnormalities: In cases of acute hepatic failure, bleeding disorders are usually associated with disseminated intravascular coagulation (DIC). Treatment for DIC with anemia requires fresh whole blood transfusion, which is preferred over packed RBC for presence of clotting factors. (Fresh whole blood is also preferred over stored blood in animals with hepatobiliary disease because ammonia tends to build up during storage.) Alternatively, if anemia is not present, fresh frozen plasma transfusion can be used. In chronic liver disease, coagulopathies are generally due to decreased production of coagulation factors. Bacterial Infections and Sepsis: Animals with acute hepatic failure and chronic hepatobiliary disease are predisposed to bacterial infections. In chronic disease, the infection is more likely to be intrahepatic, and both aerobic and anaerobic cultures should be performed. Empirical use of antibiotics should include drugs specifically active against GI flora and avoid drugs that are extensively metabolized by the liver. Appropriate choices pending culture and sensitivity include ampicillin (22 mg/kg, PO or IV, t.i.d. to q.i.d.), metronidazole (7.5 mg/kg, PO, b.i.d.), cephalexin (22 mg/kg, PO or IV, t.i.d.), enrofloxacin (2.5-5 mg/kg, PO, IM, or IV, b.i.d.) and amikacin (5 mg/kg, SC, IM, or IV, b.i.d. to t.i.d.). Nutrition: Adequate calorie intake, the bulk of energy supplied by carbohydrates (20-40% of the diet) in the form of complex carbohydrates such as rice and pasta, is recommended for most animals with liver disease. (Exceptions include cats with hepatic lipidosis and animals with hepatocutaneous syndrome.) A diet high in soluble fiber may be beneficial because fermentation of fiber in the colon, through various mechanisms, decreases ammonia production and absorption and reduces incidence of hepatic encephalopathy. Vegetable and dairy protein sources such as soy, peanuts, and cheese may be more appropriate than meat sources. Zinc may have antifibrotic and hepatoprotective properties by preventing the absorption of copper from the gut. Supplementation of zinc may be beneficial in dogs; its use in cats has not been investigated. Prevention of Progression: Although not fully understood, proposed pathogenic mechanisms that lead to the progression of liver damage include inflammatory, oxidant liver cell injury, and immunologic factors. Anti-inflammatory Drugs: Corticosteroids or azathioprine may be indicated if immune-mediated events precipitate chronic hepatobiliary disease or to decrease inflammation, which can contribute to ongoing necrosis and fibrogenesis. Azathioprine (2 mg/kg, PO, s.i.d., decreased to every 48 hr) has been recommended for use in chronic hepatobiliary disease either with or without glucocorticoids. Adverse affects of azathioprine include bone marrow suppression (that may warrant withdrawal of the drug until the bone marrow function is normal, then reducing the dose by 75%), pancreatitis, and GI toxicity. Azathioprine is not recommended in cats. Limiting Fibrosis: Hepatic fibrosis can eventually lead to cirrhosis. However, fibrosis is potentially reversible. Colchicine is both antifibrotic and anti-inflammatory. The dosage is 0.03 mg/kg, PO, s.i.d. Adverse affects of colchicine include nausea,

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vomiting, and hemorrhagic diarrhea. Colchicine is available in formulations with and without probenecid. Formulations without probenecid should be used because probenecid can cause nausea and vomiting. Zinc may also be useful in decreasing fibrosis. Portosystemic Shunts: Overview The most common circulatory anomaly of the liver in both dogs and cats is the portosystemic shunt (PSS). A PSS is a connection between the portal vessels and systemic circulation that diverts blood flow, in varying degrees, from the liver. Decreased blood flow results in liver atrophy and subsequent dysfunction. In addition, decreased liver metabolism of neurotoxins leads to clinical signs of hepatic encephalopathy. Because of this, clinical signs can be most severe postprandially, especially after a high-protein meal. High-protein meals are more frequently associated with hepatic encephalopathy in dogs than in cats. Congenital PSS are seen primarily in purebred dogs, including Miniature Schnauzers, Yorkshire Terriers, Cairn Terriers, Maltese Terriers, Scottish Terriers, Pugs, Irish Wolfhounds, Golden Retrievers, Labrador Retrievers, German Shepherd Dogs, and Poodles. In cats, congenital PSS are seen more frequently in mixed breeds, but Himalayans and Persians are affected more commonly than other purebreds. Cats and small-breed dogs usually have extrahepatic shunts, whereas large-breed dogs have intrahepatic shunts. Extrahepatic shunts arise from the portal vein, left gastric vein, or splenic vein and connect to the caudal vena cava (most common), the azygous vein, or other systemic vessels. Congenital intrahepatic shunts usually are due to failure of the fetal ductus venosus to close at birth. Acquired PSS are caused by portal hypertension. Acquired shunts are usually seen in older animals, more frequently in dogs than in cats, and are usually multiple. Acquired shunts develop to prevent fatal portal hypertension, which occurs as a result of chronic, severe, diffuse intrahepatic disease (eg, chronic hepatitis, cirrhosis, and hepatic fibrosis). The vessels involved are connections between the splenic and mesenteric veins through the renal veins, gonadal veins, or the venous sinuses within the spinal cord to the caudal vena cava. These vessels are fetal vasculature that open as a compensatory mechanism to shunt blood to lower pressure systemic circulation as a response to portal hypertension. During acquired PSS, these vessels become tortuous. Possible causes of portal hypertension in younger dogs include hepatic arteriovenous fistulas, veno-occlusive disease in Cocker Spaniels, or portal vascular atresia. Clinical Findings and Diagnosis: Animals affected with congenital PSS are often smaller than littermates, show failure to thrive, and can have other congenital abnormalities (eg, cryptorchidism in dogs and cats, heart murmurs in cats). Male cats may be more prone to congenital shunts than females. Hepatic encephalopathy is the most common clinical sign. Other clinical signs include vomiting, diarrhea, pica, nausea, anorexia, polyuria, and polydipsia. Hematuria, pollakiuria, stranguria, or urethral obstruction due to urate urolithiasis have been reported. Hypersalivation is a common clinical sign in cats; blindness and excessive vocalization have also been reported. Ascites is a common finding in acquired portosystemic shunts but is rarely seen in congenital shunts unless hypoalbuminemia is severe (50% suppression of the cortisol level to be diagnostic for PDH, while others use an absolute number (eg, 18 mg/dL are often associated with severe, life-threatening signs. Polydipsia and polyuria are the most common signs of hypercalcemia and result from an impaired ability to concentrate urine and a direct stimulation of the thirst center. Anorexia, vomiting, and constipation can also develop as a result of decreased excitability of GI smooth muscle. Decreased neuromuscular excitability may lead to signs of generalized weakness, depression, muscle twitching, and seizures. Hypercalcemia of Malignancy Malignancy is the most common cause of persistent hypercalcemia in dogs and cats. In hypercalcemia of malignancy, the hypercalcemia primarily results from increased osteoclastic bone resorption, but increased renal tubular resorption and increased intestinal absorption may also play a role. Factors that may be produced by tumors and result in humoral hypercalcemia of malignancy include PTH, PTH-related protein, transforming growth factor, 1,25-dihydroxyvitamin D, prostaglandin E2, osteoclast-activating factor, and other cytokines (interleukin-1, interleukin-2, and gamma interferon). Although many tumors have been associated with hypercalcemia in man, lymphoma, adenocarcinoma of the apocrine glands of the anal sac, and multiple myeloma are the most common tumors in animals associated with hypercalcemia of malignancy. Lymphoma (Lymphosarcoma): Lymphoma is the most common tumor associated with hypercalcemia in dogs and cats. The pathogenesis of the hypercalcemia in lymphoma may involve two general mechanisms: one is local elaboration of an osteolytic factor that induces resorption of bone and mobilization of calcium when the bone marrow is infiltrated by tumors cells; the other, probably more important, is humoral hypercalcemia in which neoplastic cells produce a humoral factor that acts at a distance from the tumor. As evidence for secretion of a humoral substance by tumor cells, increased bone resorption, phosphaturia, and urinary excretion of cyclic adenosine monophosphate (cAMP) have been documented in dogs with lymphoma. Of dogs with lymphoma, 10-40% have been reported to have concurrent hypercalcemia, and a large number of these cases also have the mediastinal form of lymphoma. Although detectable lymphadenopathy is usually present, hypercalcemia may be the first abnormality noted. A thorough physical examination, together with thoracic and abdominal radiographs, abdominal ultrasonography, multiple lymph node aspirates or biopsies, and multiple bone marrow aspirates may be necessary for diagnosis. Treatment with glucocorticoids (eg, prednisone) will lower the serum calcium concentrations; however, steroids are lympholytic and will make identification of lymphoma difficult. Although remission rates in dogs with lymphoma and hypercalcemia are not statistically different from those without hypercalcemia, survival times are considerably less, indicating that hypercalcemic lymphomas have a poorer prognosis. Adenocarcinoma of the Apocrine Glands of the Anal Sac: This tumor usually occurs in older female dogs, with hypercalcemia developing in ~90% of cases. Adenocarcinoma of the anal sac is usually malignant and has metastasized to regional lymph nodes at the time of diagnosis. Surgical resection is associated with reduction of serum calcium. Multiple Myeloma: Hypercalcemia has been associated with multiple myeloma in dogs and cats in 10-15% of cases. The presence of extensive bony lysis may also contribute to the increased serum calcium. Although serum protein concentration is usually increased in multiple myeloma, increased protein binding of calcium rarely accounts for the hypercalcemia. Primary Hyperparathyroidism Primary hyperparathyroidism results from excessive secretion of PTH by an abnormal (usually neoplastic) parathyroid gland(s). Persistent hypercalcemia is characteristic. This disease is relatively rare in dogs and cats. Etiology: Solitary adenoma of the parathyroid gland is the most common cause of primary hyperparathyroidism, whereas parathyroid carcinoma has been infrequently reported. Clinical Findings: Polydipsia, polyuria, anorexia, lethargy, and depression are the most common signs, but many animals are asymptomatic. Constipation, weakness, shivering, twitching, vomiting, stiff gait, and facial swelling are less often reported. Diagnosis: Hypercalcemia, normal to low serum phosphorus, and low urine specific gravity are the most consistent findings. Azotemia commonly develops as a consequence of moderate to severe hypercalcemia. In hypercalcemic animals that still have relatively normal renal function (normal serum creatinine and BUN concentrations), determination of serum PTH is helpful in diagnosis. Merck Veterinary Manual - Summary

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Treatment: Treatment of primary hyperparathyroidism is surgical excision of the parathyroid adenoma. Attempts to lower the serum calcium concentration with IV fluids (saline) and furosemide before surgery may be beneficial. Other Causes of Hypercalcemia Hypoadrenocorticism: Mild hypercalcemia (≤15 mg/dL) has been reported in up to 30% of dogs with hypoadrenocorticism (Addison's disease, Hypoadrenocorticism). Multiple factors may cause the hypercalcemia, including increases in calcium citrate (complexed calcium) and renal resorption of calcium, hemoconcentration (relative increase), and increased affinity of serum proteins for calcium. Although total serum calcium concentrations may be increased, the ionized fraction usually is normal. The hypercalcemia resolves quickly with successful treatment for hypoadrenocorticism. Renal Failure: Hypercalcemia develops rarely in animals with renal failure. Rodenticides and Hypervitaminosis D: Rodenticides containing cholecalciferol are a fairly common cause of hypercalcemia in dogs and cats. Hypercalcemia is often severe (serum calcium, 15-20 mg/dL), and hyperphosphatemia is common. High serum concentrations of cholecalciferol and vitamin D metabolites may provide a definitive diagnosis; however, these tests are not widely available. A low-calcium diet and restriction of milk products is recommended. Phosphate binders that do not contain calcium (ie, aluminum hydroxide) may also be helpful. In severe cases of hypercalcemia, aggressive treatment with IV fluids, furosemide, prednisone, and/or calcitonin may be necessary for several weeks. Iatrogenic Vitamin D Overdosage: Use of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) may cause hypercalcemia; a slow onset of action and prolonged duration make correct dosing difficult. Houseplants: Ingestion of certain house plants (eg, Cestrum diurnum [the day-blooming jessamine], Solanum malacoxylon , Triestum flavescens ) may contain a substance similar to vitamin D that may cause hypercalcemia when ingested. Granulomatous Diseases: A number of ganulomatous diseases (eg, systemic fungal diseases, sarcoidosis, and tuberculosis) have been associated with hypercalcemia in man and dogs. Osteolytic Lesions: Primary bone tumors (eg, osteosarcoma) and neoplastic cells within the bone marrow (eg, multiple myeloma) may occasionally produce hypercalcemia. The mechanisms whereby bony neoplasia may produce hypercalcemia include mechanical destruction by the infiltrating cells (as occurs with metastatic tumors and osteosarcoma) and local production of osteoclast-activating factor (as occurs with multiple myeloma). Principles of Treatment of Hypercalcemia The definitive treatment of hypercalcemia is correcting or removing the underlying cause. Unfortunately, the etiology may not be apparent, and supportive measures must be taken to decrease the serum calcium concentration. Fluid Therapy: Volume expansion with 0.9% saline, ~100-125 mL/kg/day, IV, decreases hemoconcentration and increases renal calcium loss by improving glomerular filtration rate and sodium excretion, which results in less calcium reabsorption. Diuretics: Loop diuretics such as furosemide (2-4 mg/kg, every 8-12 hr) will increase calcium excretion by the kidneys; however, higher doses may be needed. If dehydration is present, fluid therapy should be instituted first because hypovolemia and further hemoconcentration may worsen the hypercalcemia. Thiazide diuretics are contraindicated in hypercalcemia because they decrease calcium excretion by the kidneys and worsen the hypercalcemia. Sodium Bicarbonate: Bicarbonate given as an IV bolus (1 mEq/kg) or as a continuous infusion has been shown to decrease serum total calcium concentrations. Although the magnitude of calcium reduction is mild, alkalosis also favors the shift of ionized calcium to protein-bound calcium. Sodium bicarbonate therapy is more beneficial when combined with other treatments. Glucocorticoids: Administration of glucocorticoids (eg, prednisone, 1-2 mg/kg, b.i.d.) decreases bone resorption of calcium and intestinal calcium absorption and increases renal calcium excretion; this leads to a substantial decrease in serum calcium concentration in animals with hypercalcemia secondary to lymphoma, myeloma, hypervitaminosis D, and hypoadrenocorticism. Miscellaneous Agents: Calcitonin has been reported as an antidote to cholecalciferol toxicity, but its effect may be short (hours), requiring multiple treatments. Merck Veterinary Manual - Summary

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Hypocalcemia In Dogs And Cats: Overview Hypocalcemia causes the major clinical manifestations of hypoparathyroidism by increasing the excitability of both the central and peripheral nervous systems. Peripheral neuromuscular signs classically include muscle tremors, twitches, and tetany. Hypoparathyroidism Hypoparathyroidism is a metabolic disorder characterized by hypocalcemia and hyperphosphatemia and either transient or permanent parathyroid hormone (PTH) insufficiency. The spontaneous disorder is uncommon in dogs and rarely reported in cats. Iatrogenic injury or removal of the parathyroid glands during thyroidectomy for treatment of hyperthyroidism is the most common cause of hypoparathyroidism in cats. Diagnosis: Diagnosis of hypoparathyroidism is based on history, clinical signs, laboratory evidence of hypocalcemia and hyperphosphatemia, and exclusion of other causes of hypocalcemia (eg, hypoproteinemia, malabsorption, pancreatitis, renal failure). Determination of serum PTH concentrations might be helpful in the diagnosis of idiopathic hypoparathyroidism and may thereby eliminate the need for cervical exploratory surgery and histologic verification. Treatment: Treatment of hypoparathyroidism is directed at restoring the serum calcium concentration to the low end of the normal range. This includes use of calcium supplements and vitamin D for either iatrogenic or idiopathic forms of hypoparathyroidism. If hypocalcemic tetany or seizures are present, calcium should be administered IV immediately. For maintenance of normocalcemia, oral calcium should be administered together with a vitamin D preparation. The major complication associated with treatment of hypoparathyroidism is hypercalcemia, which develops as a consequence of overtreatment with calcium and vitamin D. If this occurs, calcium and vitamin D therapy should be temporarily discontinued, and saline and furosemide administered if hypercalcemia is severe (see principles of treatment of hypercalcemia , above). Principles of Treatment of Hypercalcemia With idiopathic hypoparathyroidism, long-term management with vitamin D (with or without calcium supplementation) is necessary. Other Causes of Hypocalcemia Puerperal Tetany: Puerperal tetany (eclampsia, Puerperal Hypocalcemia In Small Animals: Introduction) is an acute, life-threatening disease caused by an extreme fall in circulating calcium concentrations in the lactating bitch or queen. Severe hypocalcemia develops during the nursing period Hypoproteinemia: Animals with hypoalbuminemia may be hypocalcemic because of a decrease in the protein-bound fraction of calcium, but the ionized calcium fraction may remain normal. Therefore, the magnitude of hypocalcemia is usually mild, and clinical signs do not usually develop. Renal Disease: Hypocalcemia may occasionally develop in animals with renal failure. Azotemia and hyperphosphatemia result from decreased glomerular filtration rates. The hypocalcemia associated with renal failure, however, is rarely clinically significant (ie, signs do not develop). Pancreatitis: Hypocalcemia, when it occurs in animals with pancreatitis ( Acute Pancreatitis), is usually mild and subclinical. Phosphate Enema Toxicity: Hypertonic sodium phosphate enemas may result in severe biochemical abnormalities, especially when administered to dehydrated cats with colonic atony and mucosal disruption. Colonic absorption of sodium and phosphate from the enema solution, as well as transfer of intravascular water to the colonic lumen (because of the hypertonic enema), cause hypernatremia and hyperphosphatemia. Hyperphosphatemia leads to precipitation of serum calcium with resultant hypocalcemia. Clinical signs of phosphate enema toxicosis, which result from these electrolyte and fluid alterations, include shock and neuromuscular irritability. Treatment consists of IV volume expansion with an electrolyte-poor solution (eg, 5% dextrose in water), as well as treatment of hypocalcemia (see below). Principles of Treatment of Hypocalcemia Principles of Treatment of Hypocalcemia The definitive treatment for hypocalcemia is to eliminate the underlying cause. Parenteral Calcium: Hypocalcemic tetany or convulsions are indications for the immediate administration of 10% calcium gluconate, 1.01.5 mL/kg, IV, infused slowly over a 10-min period. Close monitoring is essential; if bradycardia or shortening of the Q-T interval occurs, the IV infusion should be slowed or temporarily discontinued. Oral Calcium: Merck Veterinary Manual - Summary

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Oral calcium supplementation may be beneficial in some conditions (eg, hypoparathyroidism, puerperal tetany). The Pituitary Gland : Introduction The pituitary gland (hypophysis) is composed of the adenohypophysis (anterior lobe) and the neurohypophysis (posterior lobe). Adenohypophysis: The adenohypophysis, which surrounds the pars nervosa of the neurohypophyseal system to varying degrees in different species, consists of the pars distalis, the pars tuberalis, and the pars intermedia. The pars distalis is the largest part of the adenohypophysis and contains multiple populations of endocrine cells. The pars tuberalis functions primarily as a scaffold for the capillary network of the hypophyseal portal system. The pars intermedia forms the junction between the pars distalis and pars nervosa. It contains two populations of cells in dogs, one of which synthesizes adrenocorticotropic hormone (ACTH). Secretory cells in the adenohypophysis are often subdivided into chromophils (acidophils, basophils) and chromophobes based on interaction of the secretory granules with pH-dependent histochemical stains. Acidophils are further subdivided into somatotrophs that secrete growth hormone (GH, somatotropin) and lactotrophs that secrete prolactin. Basophils include gonadotrophs that secrete both luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and thyrotrophs that secrete thyrotropic hormone (thyroid-stimulating hormone [TSH]). Chromophobes include the endocrine cells involved in the synthesis of ACTH and melanocyte-stimulating hormone (MSH), nonsecretory follicular cells, and undifferentiated stem cells. Neurohypophysis: The neurohypophysis (pars nervosa, posterior lobe) has three anatomic subdivisions. Secretion granules that contain the neurohypophyseal hormones, ie, antidiuretic hormone (ADH, vasopressin) and oxytocin, are synthesized in the hypothalamus but are released into the bloodstream in the pars nervosa. Hyperadrenocorticism (Cushing's disease) Clinical Findings: Miniature Poodles, Dachshunds, Boxers, Boston Terriers, and Beagles are breeds at increased risk of developing hyperadrenocorticism. Laboratory Abnormalities: In dogs, serum chemistry abnormalities associated with hypercortisolemia include increased serum alkaline phosphatase and ALT, hypercholesterolemia, hyperglycemia, and decreased BUN. The hemogram is often characterized by evidence of regeneration (erythrocytosis, nucleated red blood cells) and a classic “stress leukogram” (mature neutrophilia, lymphopenia, and eosinopenia). Basophilia is occasionally seen. Many dogs have evidence of urinary tract infection without pyuria (positive culture), bacteriuria, and proteinuria resulting from glomerulosclerosis. Thyroid status is often affected and is evidenced by decreased basal thyroxine (T4) and triiodothyronine (T3), caused by euthyroid sick syndrome and by an attenuated response to TSH stimulation due to the effect of cortisol and overcrowding on pituitary thyrotrophs. Overt diabetes mellitus may result from the insulin antagonism caused by hypercortisolemia in ~25% of dogs with hyperadrenocorticism and in an even higher percentage of cats. In addition, hyperadrenocorticism can be a cause of insulin resistance and poor glycemic control in diabetic dogs. Diagnosis: The low-dose dexamethasone suppression (LDDS) test is the screening test of choice for hyperadrenocorticism in dogs. As a screening test for the diagnosis of naturally occurring hyperadrenocorticism, the ACTH stimulation test has a diagnostic sensitivity of ~80-85% and a higher specificity than the LDDS test. Measurement of endogenous plasma ACTH concentrations is the most reliable method of differentiating between PDH and adrenal tumors. Dogs with adrenal tumors have low to undetectable ACTH concentrations; in contrast, dogs with PDH have normal to increased ACTH concentrations. The high-dose dexamethasone suppression (HDDS) test works on the principle that ACTH secretion has already been suppressed maximally in dogs with functioning adrenal tumors; therefore, administration of dexamethasone, no matter how high the dose, will not suppress serum cortisol concentrations. In dogs with PDH, however, high doses of dexamethasone are able to suppress ACTH and hence cortisol secretion. One caveat is that dogs with pituitary macroadenomas (15-50% of dogs with PDH) fail to suppress on the HDDS test. Diagnostic imaging of the pituitary or adrenal glands can be accomplished via abdominal radiography, ultrasonography, computerized tomography, or magnetic resonance imaging. Abdominal radiographs should be performed in all dogs that do not suppress on an HDDS; in ~30-50% of dogs with adrenal tumors, a mineralized mass in the area of the adrenal glands can be seen. Treatment:

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Dogs with PDH may be treated using the adrenolytic agent mitotane (o,p'-DDD), beginning with an induction dose of 25-50 mg/kg/day for 7-10 days. Dogs should be monitored for signs of hypoadrenocorticism, such as anorexia, vomiting, and diarrhea; if such signs occur, mitotane therapy should be discontinued and glucocorticoids administered. Water consumption may be measured to provide an endpoint for therapy and should decrease to 1.025 in those animals with only a partial ADH deficiency or with antagonism to ADH action caused by hypercortisolism. There is little change in specific gravity in those animals with a complete lack of ADH activity, whether due to a primary loss of ADH or to unresponsiveness of the kidneys. If osmolality is measured, the ratio of urine to plasma osmolality after water deprivation is >3 in normal animals, 1.8-3 in those with moderate ADH deficiency, and 2 in animals with primary ADH deficiency, between 1.1 and 2 in those with inhibitors to ADH action, and 20 u/cat/day). Hypercholesterolemia and mild increases in liver enzymes are attributed to the diabetic state. Hyperphosphatemia without azotemia is also a common clinicopathologic finding. Urinalysis is unremarkable except for persistent proteinuria. Lesions: Gross necropsy findings in acromegalic cats may include a large expansile pituitary mass, hypertrophic cardiomyopathy with marked left ventricular and septal hypertrophy (early) or dilated cardiomyopathy (late), hepatomegaly, renomegaly, degenerative joint disease, lumbar vertebral spondylosis, moderate enlargement of the parathyroid glands, adrenocortical hyperplasia, and diffuse enlargement of the pancreas with multifocal nodular hyperplasia. Histopathologic examination of the endocrine glands reveals acidophil adenoma of the pituitary; adenomatous hyperplasia of the thyroid gland; and nodular hyperplasia of the adrenal cortices, parathyroid glands, and pancreas. Treatment and Prognosis: Medical therapy in man includes the use of dopamine agonists, such as bromocriptine, and somatostatin analogs (octreotide). The short-term prognosis in cats with untreated acromegaly is fair to good. Insulin resistance is generally controlled satisfactorily by using large doses of insulin divided into several daily doses. Mild cardiac disease can be managed with diuretics and vasodilators. Eventually however, the long-term prognosis is relatively poor, and most cats die of congestive heart failure, chronic renal failure, or signs of an expanding pituitary mass. The long-term prognosis may improve with early diagnosis and treatment. The Thyroid Gland : Introduction Physiology: Thyroid hormones are the only iodinated organic compounds in the body. Thyroxine (T4) is the main secretory product of the normal thyroid gland; however, the gland also secretes 3,5,3'-triiodothyronine (T3), reverse T3, and other deiodinated metabolites. T3 is ~3-5 times more potent than T4, while reverse T3 is thyromimetically inactive. Although all T4 is secreted by the thyroid, a considerable amount of T3 is derived from T4; therefore, T4 has been called a prohormone. Thyroid hormones are water-insoluble lipophilic compounds that are bound to plasma proteins (thyroxine-binding protein, thyroxine-binding prealbumin [transthyretin], and albumin). The major function of the thyroid-hormone-binding proteins is probably to provide a hormone reservoir in the plasma and to “buffer” hormone delivery into tissue. In the healthy euthyroid animal, 0.1% of total serum T4 is free (not bound to thyroid-hormone-binding proteins), whereas ~1% of circulating T3 is free. Action of Thyroid Hormones: Effects of thyroid hormones generally are divided into two categories: those that manifest within minutes to hours after hormone receptor binding and do not require protein synthesis, and those that manifest later (usually >6 hr) and require synthesis of new proteins. About half the increase in oxygen consumption produced by thyroid hormones is related to activation of the plasma-membrane-bound Na+/K+ATPase; thyroid hormones also stimulate mitochondrial oxygen consumption. Thyroid hormones, in physiologic quantities, are anabolic; in conjunction with growth hormone and insulin, protein synthesis is stimulated and nitrogen excretion is reduced. However, in excess (hyperthyroidism), they can be catabolic; gluconeogenesis, protein breakdown, and nitrogen wasting are increased. Hypothyroidism In hypothyroidism, impaired production and secretion of the thyroid hormones result in a decreased metabolic rate. Etiology: Although dysfunction anywhere in the hypothalamic-pituitary-thyroid axis may result in thyroid hormone deficiency, >95% of clinical cases of hypothyroidism in dogs appear to result from destruction of the thyroid gland itself (primary hypothyroidism). The two most common causes of adult-onset primary hypothyroidism in dogs include lymphocytic thyroiditis and idiopathic atrophy of the thyroid gland. Lymphocytic thyroiditis, probably immune-mediated, is characterized histologically by a diffuse infiltration of the gland by lymphocytes, plasma cells, and macrophages, and results in progressive destruction of follicles and secondary fibrosis. Idiopathic atrophy of the thyroid gland is characterized

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histologically by loss of thyroid parenchyma and replacement with adipose tissue. (See also autoimmune thyroiditis, Diseases Involving Cell-mediated Immunity.) In cats, the most common cause of hypothyroidism is iatrogenic as a result of treatment for hyperthyroidism with radioiodine, surgical thyroidectomy, or use of an antithyroid drug. Clinical Findings: Although onset is variable, hypothyroidism is most common in dogs 4-l0 yr old. It usually affects mid- to large-size breeds and is rare in toy and miniature breeds. Breeds reported to be predisposed include the Golden Retriever, Doberman Pinscher, Irish Setter, Miniature Schnauzer, Dachshund, Cocker Spaniel, and Airedale Terrier. There does not appear to be a sex predilection, but the risk of developing hypothyroidism appears to be higher in spayed females than in intact females. Difficulty in maintaining body temperature may lead to frank hypothermia; the classic hypothyroid dog is a heatseeker. Alterations in the skin and coat are common; dryness, excessive shedding, and retarded regrowth of hair are usually the earliest dermatologic changes. Nonpruritic hair thinning or alopecia (which is usually bilaterally symmetrical) that may involve the ventral and lateral trunk, the caudal surfaces of the thighs, dorsum of the tail, ventral neck, and the dorsum of the nose occurs in about two-thirds of dogs with hypothyroidism. In moderate to severe cases, thickening of the skin occurs secondary to accumulation of glycosaminoglycans (mostly hyaluronic acid) in the dermis. In such cases, myxedema is most common on the forehead and face, resulting in a puffy appearance and thickened skin folds above the eyes. In intact dogs, hypothyroidism may cause various reproductive disturbances. In females, these include failure to cycle (anestrus) or sporadic cycling, infertility, abortion, or poor litter survival; and in males, lack of libido, testicular atrophy, hypospermia, or infertility. Diagnosis: Hypothyroidism in dogs is probably one of the most overdiagnosed diseases in small animal practice. The clinical signs of many diseases and conditions can mimic those of hypothyroidism, and some of these clinical signs, even in dogs with normal thyroid function, can improve after administration of exogenous thyroid hormone. In addition, several nonthyroidal factors can lead to low serum thyroid hormone levels in euthyroid dogs. Definitive diagnosis of canine hypothyroidism requires careful attention to clinical signs, routine laboratory testing, and demonstration of low serum concentrations of total or free thyroid hormones that are unresponsive to TSH administration. The classic hematologic finding associated with hypothyroidism is a normocytic, normochromic, nonregenerative anemia. The classic serum biochemical abnormality is hypercholesterolemia, which occurs in ~80% of dogs with hypothyroidism. Because serum cholesterol determination is a sensitive and inexpensive biochemical marker for hypothyroidism in the dog, it is an excellent screening test. Other clinicopathologic abnormalities may include high serum concentrations of triglycerides, alkaline phosphatase, and creatine kinase. Because T3 is the most potent thyroid hormone at the cellular level, it would seem logical to measure its concentration for diagnostic purposes. However, serum T3 concentrations may be low, normal, or (occasionally) high in dogs with documented hypothyroidism. The diagnostic value of a serum T3 determination appears particularly weak during early thyroid failure because the “failing thyroid” tends to increase the relative synthesis and secretion of T3 over T4. In the hypothyroid dog in which values for serum T3 are high, anti-T3 antibodies, which produce spurious results in most T3 radioimmunoassays, should be suspect. The determination of basal serum total T4 concentration by radioimmunoassay techniques may provide important information to rule out a diagnosis of hypothyroidism. Because T4 is produced only by the thyroid gland, hypothyroid dogs can, in most cases, be distinguished from normal dogs based on a low resting serum total T4 concentration. However, many nonthyroidal illnesses and certain drugs may also lower baseline serum T4 concentrations in dogs. Even when historical and physical findings do not suggest other factors that would lower serum T4, the diagnosis of hypothyroidism should be confirmed by a dynamic thyroid function test (eg, TSH stimulation test) or by determining free T4, when possible. Administration of exogenous bovine TSH followed by measurement of serum T4 provides important diagnostic information because it tests thyroid secretory reserve. The TSH stimulation test is the most definitive noninvasive test to diagnose primary hypothyroidism. A widely used protocol is to collect a baseline blood sample for serum T4 determination, administer TSH at 0.1 u/kg, IV (up to a maximum dose of 5 u), and then collect a serum sample for T4 determination 6 hr after injection. In primary hypothyroidism, the post-TSH serum T4 concentration remains below the normal range for basal T4 (1 yr awaiting a new host, ticks infected in their previous instar can still be infective after long periods of hibernation. The ready transmission of infection by injecting infected blood suggests that the organism could be transmitted mechanically by biting insects, and if the organisms reported to cause a similar disease in ruminants in India and South Africa are indeed E phagocytophila , it is most likely that ticks other than I ricinus are involved. Clinical Findings: After infestation with infected ticks, the incubation period may range between 5 and 14 days, but after injection with infected blood, the incubation period is 2-6 days. In sheep, the main clinical sign is a sudden fever (40.5-42.0°C [105108°F]) for 4-10 days. Other signs are either absent or mild, but the animals generally appear dull and may lose weight. Respiratory and pulse rates are usually increased, and a cough often develops. The disease occurs as an annual minor epidemic when dairy heifers and cows are turned out to pasture in the spring and early summer. Within days, the cows are dull and depressed, with a marked loss of appetite and milk yield. Affected cows usually suffer from respiratory distress and coughing. Clinical signs are more obvious and last longer in newly purchased animals than in home-bred animals. Often, veterinary advice is sought after an abrupt fall in milk yield. Abortions affect susceptible ewes and cows newly introduced onto tick-infested pastures during the last stages of gestation, with abortions occurring 2-8 days after the onset of fever. Except for aborting ewes, death due to TBF is rare. Perhaps the most significant effect of TBF infection is its serious impairment of humoral and cellular defense mechanisms, which results in increased susceptibility to secondary infections such as tick pyemia, pneumonic pasteurellosis, looping ill, and listeriosis. Lesions: The disease is characterized by transient but distinct hematologic changes. A modest neutrophilia develops 2-4 days after natural or experimental infection and is followed by a severe leukopenia due to lymphocytopenia and neutropenia. The lymphocytopenia lasts for 4-6 days, while the neutropenia develops more progressively and becomes more marked ~10 days after infection. Both T and B lymphocytes are reduced. The number of circulating eosinophils is also depressed for up to 2 wk. After the febrile period has subsided, the number of monocytes may increase. At the peak of reaction, >90% of circulating neutrophils and eosinophils may be infected. The monocytes are predominantly infected during the later stages of bacteremia, while the granulocytes are usually infected throughout the period of bacteremia. Diagnosis: In sheep, the onset of high fever in tick-infested areas during the spring and summer in association with hematologic changes and the presence of inclusions within granulocytes is diagnostic. TBF could be established retrospectively as a cause of abortions by demonstrating a rise in antibody titers by the indirect immunofluorescent test. Control: There are three important aspects of control: vector control, immunity, and chemotherapy. Effective control can be achieved by eliminating or markedly reducing contact with the tick vector either by grazing sheep and cattle on tick-free pastures in lowland areas or by use of acaricides. The short-acting oxytetracyclines are regarded as the most effective because other antibiotics such as penicillin, streptomycin, and ampicillin do not prevent relapses. Sulfamethazine has also proved useful. If dairy cattle are treated with oxytetracyclines within a few days of infection, the pyrexia is reduced quickly and milk yield restored. In enzootic areas, treatment with long-acting tetracyclines may be used as a prophylactic measure against TBF. Canine Distemper: Introduction (Hardpad disease) Canine distemper is a highly contagious, systemic, viral disease of dogs seen worldwide. It is characterized by a diphasic fever, leukopenia, GI and respiratory catarrh, and frequently pneumonic and neurologic complications. The disease occurs in Canidae (dogs, foxes, wolves), Mustelidae (eg, ferret, mink, skunk), most Procyonidae (eg, raccoon, coatimundi), and some Viveridae (binturong). Etiology and Pathogenesis: Canine distemper is caused by a paramyxovirus closely related to the viruses of measles and rinderpest. The enveloped virus is sensitive to lipid solvents and most disinfectants and is relatively unstable outside the host. The main route of infection is via aerosol droplet secretions from infected animals. Some infected dogs may shed virus for several months. Virus replication initially occurs in the lymphatic tissue of the respiratory tract. A cell-associated viremia results in infection of all lymphatic tissues, which is followed by infection of respiratory, GI, and urogenital epithelium, as well as the CNS. Disease follows virus replication in these tissues. The degree of viremia and extent of spread of virus to various tissues is moderated by the level of specific humoral immunity in the host during the viremic period. Clinical Findings: Merck Veterinary Manual - Summary

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A transient fever usually occurs 3-6 days after infection and there may be a leukopenia (especially lymphopenia) at this time, but these signs may go unnoticed. The fever subsides for several days before a second fever occurs, which lasts 12 times weekly, within 1-2 hr of eating. The vomitus may be tinged with bile. In cats, vomiting may be the sole sign; dogs may also have loose feces intermittently. Skin lesions and poor coat are commonly associated with food allergies in cats but less commonly in dogs. Food allergy may be a cause of diarrhea in newly weaned piglets, although the supporting evidence is not clear; the diarrhea is usually treated as an infection rather

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than an allergy. Eosinophilic enteritis is the most severe form of allergic intestinal disease. It manifests by moderate to severe inflammation of the intestines and a pronounced eosinophilia. Dogs should be fed low-protein feeds that contain as few ingredients as possible. Low doses of glucocorticoids given daily or every other day also can provide excellent relief for dogs that are not helped by dietary changes. Allergic enteritis in cats is treated by feeding exclusively meat protein. Ground, cooked turkey and lamb are good hypoallergenic foods for cats. Atopic dermatitis is a pruritic, chronic skin disorder that occurs in many species but has been studied mostly in dogs. Animals with atopic dermatitis have a genetic predisposition that leads to excessive production of reaginic (IgE) antibodies. It has been estimated that ~10% of all dogs suffer from atopy, with a breed predisposition in terriers, Dalmatians, and retrievers. Atopic dermatitis of dogs often is due to inhaled allergens, eg, pollens, molds, and danders. The skin is the target tissue in dogs. Atopic dogs often chew at their feet and axillae. Excessive sweating is especially noticeable in the hairless areas. The skin lesions are greatly increased in severity by licking, scratching, and secondary bacterial infection. Atopic skin lesions in cats are either miliary (small scabs) and widespread, or larger and more localized. Localized lesions are often pruritic. In cats, food allergens probably are a more common cause of skin lesions than are inhaled allergens. Sweet itch is a seasonal allergic dermatitis of horses associated with certain insect bites, especially night-feeding Culicoides . Intensely pruritic lesions appear along the dorsum from the ears to tail head and perianal area. Similar allergic skin reactions to insect bites can be seen about the ears and face of cats and dogs. Hyposensitization consists of an extended series of injections of the offending allergen until improvement is noted; it is effective in ~60% of dogs with atopic dermatitis. If hyposensitization fails, or is not used, alternate-day glucocorticoid therapy is beneficial. Antihistamines are less effective in stopping the clinical manifestation of the disease. Autoimmune Hemolytic Anemia and Thrombocytopenia These are the most common Type II reactions. They can be associated with systemic lupus erythematosus (SLE [more common in dogs]) or with lymphoreticular malignancies (more common in horses and cats). Drugs, vaccines, or infections also can precipitate attacks of hemolytic anemia or thrombocytopenia in most species. Rickettsial organisms may be found responsible for many of the “idiopathic” immune-mediated disorders. Autoimmune hemolytic anemia (AIHA) has four basic forms: peracute, acute or subacute, chronic, and pure red cell aplasia. Most forms are treatable, and relapses are uncommon. Peracute AIHA is seen mainly in middle-aged, larger breeds of dogs. Affected dogs are acutely depressed, and within 24-48 hr, there is a fulminating decrease in the packed cell volume (PCV) with bilirubinemia and variable icterus and sometimes hemoglobinuria. Initially, the anemia is nonresponsive, but it becomes responsive within 3-5 days. Thrombocytopenia and thrombotic phenomena may be accompanying features. The Coombs' test is often negative, and spherocytes may or may not be present, but in-tube or slide agglutination of RBC is marked. The autoagglutination is not dispersed by saline dilution, hence the term hemolytic anemia with in-saline agglutinins. The serum usually contains autoantibodies that cause agglutination of most donor RBC (including heterospecies). The prognosis of peracute AIHA is poor even with prompt and vigorous therapy. The most effective therapy is the immediate use of high dosages of glucocorticoids plus cyclophosphamide. Incompatible blood transfusions should be avoided if possible. If incompatible blood must be used, the animal should first be heparinized and maintained on heparin for the first 10 days. Even without transfusion, heparinization may be beneficial for the first 2 wk or more. Acute AIHA is the most common form of the disease, with a breed predilection in Cocker Spaniels. Initial signs usually are pallor and fatigue, and less commonly, icterus. Hepatosplenomegaly is a prominent sign. The WBC count often is increased due to bone marrow hyperplasia. Autoagglutination of RBC is uncommon, and the Coombs' test is generally positive. These animals usually respond well to glucocorticoid therapy. If a favorable response is not seen within 7-10 days, cytotoxic drugs (cyclophosphamide or azathioprine) should be added to the regimen. Chronic AIHA differs from the acute form in that the PCV falls to a constant level and remains there for weeks or months. The bone marrow is either normal or hyperresponsive, and the Coombs' test is often negative. Chronic AIHA is relatively more common in cats than in dogs. Usually, the anemia is responsive early in the course of disease but responds minimally or not at all by the time it becomes severe. Initial treatment is with glucocorticoids; if there is no response within 2 wk, cytotoxic drugs are added to the regimen. Pure red cell aplasia is a variant of the above disorders and is most common in dogs. It occurs in two forms, one in post-weanling to adolescent puppies and the other in adults. Unlike AIHA, the bone marrow shows a selective depression of erythroid elements; granulocytes and platelets are unaffected. Therefore, the peripheral anemia is unresponsive. The immune attack apparently is directed at RBC precursors, and the Coombs' test is usually negative. However, there is often some difficulty in identifying compatible donors. Treatment is usually as for chronic AIHA. Autoimmune thrombocytopenia is common, especially in dogs. It is more common in females than males. The most frequent clinical signs are hemorrhages of the skin and mucous membranes. Melena, epistaxis, and hematuria may be accompanying features and can cause profound anemia. Hemolytic anemia and thrombocytopenia sometimes occur together. Autoimmune thrombocytopenia usually is diagnosed on the basis of low peripheral platelet counts in the face of a Merck Veterinary Manual - Summary

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pronounced megakaryocytosis in the marrow. Occasionally, however, megakaryocytes may be selectively absent from the marrow. This condition is analogous to pure red cell aplasia. Animals with autoimmune thrombocytopenia that show only petechial and ecchymotic hemorrhages, with no significant blood loss and megakaryocytes in the marrow, are usually treated initially with glucocorticoids alone. The clinical signs should abate and the platelet count begin to rise after 5-7 days. If the platelet count has not increased significantly by days 7-10, either cyclophosphamide, azathioprine, or vincristine can be added to the glucocorticoid regimen. In animals with megakaryocytes in the marrow and severe blood loss, a more rapid response to therapy is desirable. Such animals are treated with a single injection of vincristine combined with daily glucocorticoids; a favorable response usually occurs after 3-5 days. If the blood loss is life-threatening, platelet-rich whole blood should be administered. Splenectomy may be helpful; it is seldom curative by itself but may allow use of lower and safer dosages of immunosuppressive drugs. Cold agglutinin (hemolytic) disease is an AIHA that has been recognized most often in dogs and horses. It is often idiopathic but can be secondary to a chronic infection, other autoimmune diseases, or a neoplastic process. The IgM autoantibodies can be agglutinating or nonagglutinating. Complete agglutination is not seen at body temperature but rather at some lower temperature. The disease is more frequent in colder climates and during colder seasons. Initial signs may be of a hemolytic disease or, in the agglutinating type, there also may be microcapillary stasis with subsequent acrocyanosis and necrosis of the nose, tips of the ears and tail, digits, scrotum, and prepuce. Diagnosis is based on a reversible autoagglutination that occurs only at a cool temperature. The direct Coombs' reaction is usually negative for IgG, frequently positive for C3, and usually positive for IgM if the reaction is performed in the cold. Mortality is high. In the absence of precipitating disorders, eg, infection or neoplasia, the disease is best controlled with high doses of glucocorticoids used in combination with cyclophosphamide. Cyclophosphamide is withdrawn when the anemia disappears and cold agglutinins are no longer detected.

Autoimmune Skin Disorders In these immunologic skin disorders, antibodies are directed against intracellular cement substances at the basal cell layer, which results in separation of the epidermal cells (acantholysis). Pemphigus vulgaris is rarer than pemphigus foliaceus. It is characterized by bullous lesions along the mucocutaneous junctions of the mouth, anus, prepuce, and vulva, and in the oral cavity. Other areas of the skin are only mildly involved.

Because the epidermis of animals is relatively thin (compared with human skin), the bullae rupture rapidly and form erosions; consequently, characteristic bullae are seldom seen. The bullae occur as a result of suprabasilar acantholysis. Secondary bacterial infection often complicates the lesions, and if untreated, the disorder is often fatal. It is treated with high doses of glucocorticoids alone or in combination with other drugs such as cyclophosphamide, azathioprine, or gold salts. The disease is difficult to maintain in remission, and the long-term prognosis is fair to poor. Pemphigus foliaceus is more common in dogs than in cats and horses but is still an uncommon disease. It is characterized clinically by erosions, ulcerations, and thick encrustations of the skin and mucocutaneous junctions.

The absence of lesions in the mouth, and the widespread thick, crusty nature of the skin lesions, tend to differentiate pemphigus foliaceus from pemphigus vulgaris. As in pemphigus vulgaris, autoantibodies are present in the skin and react with intracellular cement substance. These autoantibodies cause a separation of the cornified from uncornified cell layers. High doses of glucocorticoids are used initially, but low-dose, alternate-day therapy is used once the disease is under control. More potent immunosuppressive drugs such as cyclophosphamide or azathioprine are used with glucocorticoids in cases unresponsive to steroids. Gold salts, in conjunction with low doses of glucocorticoids, are sometimes helpful in maintaining remission in animals in which steroids alone are ineffective. Animals that respond poorly to initial therapy, or require high dosages of drugs to control lesions, have a poor long-term prognosis. Bullous pemphigoid has been recognized in dogs, most often in Collies and Doberman Pinschers. Lesions are often widespread but tend to be concentrated in the groin. The involved skin resembles a severe scald. Bullae also may be seen; they are subepidermal and may be full of eosinophils.

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Autoantibodies to the basal lamina proteins are seen in appropriately immunohistopathologic sections. The treatment of choice is prednisolone and azathioprine used in combination; remission is frequent, but continuous drug therapy at relatively high dosages may be required to keep the disease under control. The long-term prognosis is poor. Diseases Involving Immune Complexes (Type III reactions) Immune complex disorders are among the most common of the immunologic diseases. They may be idiopathic or of secondary origin. The site of deposition of the immune complexes determines the nature of the disease. Glomerulonephritis ( Glomerular Disease , Glomerular Disease) is caused by deposition of antigen-antibody complexes in the subendothelial or subepithelial surface of the glomerular basement membrane. Secondary glomerulonephritis occurs as a side effect of chronic infectious, neoplastic, or immunologic disorders. Animals with idiopathic glomerulonephritis (>50% of cases) usually have signs of renal disease, whereas secondary glomerulonephritis is often a relatively minor part of a more serious disease. Systemic lupus erythematosus (SLE) occurs in dogs, is rare in cats, and has been reported in large animals. It has two immunologic features: immune complex disease and a heightened antibody responsiveness with a tendency to produce autoantibodies. Therefore, it is a combination of Types II and III diseases. Antibodies to nucleic acid are the diagnostic hallmark of SLE, but in some individuals, antibodies to RBC, platelets, lymphocytes, clotting factors, immunoglobulin (rheumatoid factors), and thyroglobulin also may be present. These autoantibodies, in particular those to nucleic acids, are not always pathogenic by themselves. Rather, they should be considered markers of the disease. Although combinations of autoantibodies and self-antigens may contribute to the total pool of immune complexes, they are not the sole source of immune complexes. Usually, either the immune complex or the autoantibody aspect of the disease predominates in a given animal. Immune complex deposition around small blood vessels leads to synovitis, dermal reactions, oral erosions and ulcers, myositis, neuritis, meningitis, arteritis, myelopathy, glomerulonephritis, and pleuritis. Glomerulonephritis is one of the major life-threatening complications of SLE in cats, but not in dogs. Autoimmune hemolytic anemia or thrombocytopenia, or both, are the most common autoantibody manifestations of SLE in animals. SLE is characterized by the presence of antinuclear antibodies (ANA), and tests for these or the associated LE cells may help in diagnosis. However, some healthy animals may have ANA, and not all animals with SLE have detectable ANA in their blood. Diagnosis of SLE should be based on the entire clinical syndrome—not just on the presence or absence of ANA. SLE usually can be treated with glucocorticoids. Cyclophosphamide or azathioprine, or both, are used in combination with glucocorticoids in animals with SLE that is difficult to control with glucocorticoids alone. Purpura hemorrhagica of horses is a form of nonthrombocytopenic purpura ( Acquired Thrombocytopenia) that often is a sequela of an earlier Streptococcus equi respiratory infection; it is mediated by immune complexes of antibody and streptococcal antigen in vascular basement membranes.

Anterior uveitis ( Anterior Uvea) often involves immune-complex-mediated reactions; it frequently occurs in the recovery stage of infectious canine hepatitis ( Infectious Canine Hepatitis: Introduction) due to the reaction of serum antibodies with uveal endothelial cells that contain canine adenovirus 1. Similarly, equine uveitis ( Equine Uveitis: Introduction) or anterior uveitis of horses may be associated with immunologic reactions to Leptospira or Onchocerca spp . Uveitis caused by Toxoplasma and feline infectious peritonitis virus infections of cats also has an immunologic basis. Immune Deficiency Diseases Deficiencies in phagocytosis often manifest as an increased susceptibility to bacterial infections of the skin, respiratory system, and GI tract. These infections respond poorly to antibiotics. Leukocyte Adhesion Deficiency (Canine Granulocytopathy Syndrome) Merck Veterinary Manual - Summary

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This primary immunodeficiency disorder is an autosomal recessive trait. Selective Immunodeficiencies Rottweiler puppies have a breed predilection for severe and often fatal canine parvovirus infections. Persian cats have a predilection toward severe, and sometimes protracted, dermatophyte infections. In some Persian cats, the fungal infections invade the dermis and cause granulomatous disease (mycetomas). Mink with the Aleutian coat color mutation are susceptible to chronic parvovirus infection and develop a disorder called Aleutian mink disease. Other strains of mink are susceptible to infection with this virus but do not develop clinical disease. Long-nosed breeds, in particular German Shepherd Dogs and shepherd-crosses, are prone to develop focal aspergillosis in the nasal passages. Systemic aspergillosis is seen almost exclusively in German Shepherd Dogs, and more commonly in Western Australia than elsewhere. It is characterized by fungal pyelonephritis, osteomyelitis, and diskospondylitis. Viral-induced Immunodeficiencies Canine distemper virus causes a profound combined immunodeficiency in affected puppies. The infection is associated with a progressive decline in levels of antibody globulin and increased susceptibility to agents normally contained by cellular immunity, eg, Toxoplasma , Nocardia . Parvoviral infection in both dogs and cats causes a profound and transient depression in the number of neutrophils and in lymphocyte responsiveness. Feline leukemia virus (FeLV) infection is associated with acquired immunodeficiency and increased incidence of secondary and opportunistic infections. Acquired immunodeficiency in FeLV infection is multifactorial and broad in nature. Infected cats can have deficiencies of neutrophils, decreased synthesis of antibodies (especially to bacterial antigens), decreased cellular immunity, and variable levels of complement. Immune responses to FeLV infection also appear to inhibit ongoing feline infectious peritonitis (FIP) virus immunity specifically, which leads to reactivation of quiescent FIP. Simian immunodeficiency virus (SIV) is a lentivirus with considerable genetic homology to human immunodeficiency virus (HIV), the cause of AIDS in man. Transmission between infected and noninfected monkeys is probably by bites and in utero exposure. SIV is not present in native populations of Asian primates. The immunosuppression associated with SIV can last for weeks or years. Encephalitis (usually asymptomatic except for wasting) and lymphomas are frequent sequelae of SIV infection in macaques. Infected animals, whether healthy or diseased, carry the infection for life. Because the infection is lifelong, the presence of serum antibodies to SIV indicates the presence of virus in the body. Feline immunodeficiency virus (FIV, originally feline T-lymphotropic lentivirus) is a related lentivirus that has been identified in domestic cats and cheetahs. The virus is shed mainly in the saliva, and the principal mode of transmission is through bites. Free-roaming (feral and pet), male, and aged cats are at the greatest risk of infection. After infection, there is a transient period of fever, lymphadenopathy, and neutropenia. Cats with acquired immunodeficiency induced by FIV suffer from chronic secondary and opportunistic infections of the respiratory, GI (including mouth), and urinary tracts, as well as the skin. FIV-infected cats have a higher than expected incidence of FeLV-negative lymphomas, usually of the B-cell type, and myeloproliferative disorders (neoplasias and dysplasias). Cats remain infected for life; the presence of serum antibodies is directly correlated with the ability to isolate virus from blood cells and saliva. Tumors of the Immune System Lymphomas may be either T cell or B cell in origin. Most cases of canine lymphosarcoma, Marek's disease, calf leukosis, and feline leukemia are of T-cell origin, as are thymomas. Thymomas, which are relatively uncommon in domestic animals, generally cause loss of condition and respiratory distress. They are commonly confirmed by radiography. Many T-cell lymphomas are associated with a simultaneous immunosuppression manifest by a predisposition to recurrent infections. Adult bovine and ovine leukosis, alimentary feline leukemia, and avian leukosis are usually of B-cell origin. Under some circumstances, neoplastic B cells may develop into plasma cells. Plasma-cell tumors are known as myelomas. Because neoplastic plasma cells can secrete immunoglobulin products, they give rise to gammopathies. Gammopathies Gammopathies are conditions in which serum immunoglobulin levels are greatly increased. They can be classified either as polyclonal, which involves an increase in all major immunoglobulin classes, or as monoclonal if they involve only a single homogeneous immunoglobulin. Polyclonal gammopathies in animals are seen in chronic pyodermas; chronic viral, bacterial, or fungal infections; granulomatous diseases; abscessation; chronic parasitic infections; chronic rickettsial diseases, such as tropical canine pancytopenia; chronic immunologic diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and myositis; or with neoplasia. They also may be idiopathic. In some animals, the gammopathy may appear initially to be monoclonal Merck Veterinary Manual - Summary

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because of a predominance of one immunoglobulin class (usually IgG). Examples of this phenomenon have been seen in cats with noneffusive feline infectious peritonitis and in dogs with chronic tropical canine pancytopenia. Monoclonal gammopathies are characterized by the presence of a homogeneous serum immunoglobulin protein. Uninvolved immunoglobulin classes are usually depressed. Monoclonal gammopathies are either benign (ie, associated with no underlying disease), or they may be associated with immunoglobulin-secreting tumors. In man, benign gammopathies may become malignant at a later date; in other animals, they are rare and are not associated with a demonstrable tumor or clinical illness. Tumors that secrete monoclonal antibodies originate either from plasma cells (myeloma) or lymphoblasts (lymphosarcoma). Plasma-cell myelomas can secrete intact proteins of any immunoglobulin class, or immunoglobulin subunits (light chains or heavy chains). Myeloma proteins in dogs are commonly IgG or IgA types and less commonly IgM. Myelomas of the IgA type are particularly common in Doberman Pinschers. Monoclonal immunoglobulin produced by lymphosarcoma are often of the IgM class, regardless of species. Myeloma proteins in cats and horses usually are IgG and, uncommonly, IgM, IgG (T) (horses), or IgA. Amyloidosis can be due to increased immunoglobulin catabolism. Some IgM monoclonal proteins act as cryoglobulins and aggregate in vitro and in vivo when the plasma is cooled. Animals with cryoglobulinemia often develop gangrenous sloughs of the ear tips, eyelids, digits, and tip of the tail, especially during cold weather. (See also cold hemolytic disease, Autoimmune Hemolytic Anemia and Thrombocytopenia .) Myelomas that produce autoantibodies to various tissues have been identified in man, but not in other animals. Immunoglobulin-secreting tumors usually are treated with glucocorticoids and alkylating drugs. The prognosis for remission after therapy is much better in dogs than cats. Even in dogs, however, the long-term prognosis is poor, and relapse is common after 6-12 mo. Plasmapheresis may be needed to lower serum viscosity in animals with clinical signs of hyperviscosity syndrome.

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Integumentary System Dermis: Except in horses, apocrine glands do not appear to be innervated. Appendageal System: The hair follicles of dogs, cats, sheep, and goats are compound, ie, the follicles have a central hair surrounded by 3-15 smaller hairs all existing from a common pore. The hair follicles of horses and cattle are simple, ie, the follicles have one hair emerging from each pore. Animals with compound hair follicles are born with simple hair follicles that develop into compound hair follicles. The growing stage of the hair is referred to as anagen and the resting stage (mature hair) is referred to as telogen. The transitional stage between anagen and telogen is catagen. Animals normally shed their hair coat in response to changes in temperature and photoperiod; most animals undergo a shed in the early spring and early fall. Hormones have a significant effect on hair growth. Thyroxine initiates hair growth, and glucocorticoids inhibit hair growth. The effect of sex hormones on hair growth is not well understood; the primary function of sex hormones is not to produce hair. Sebum is a complex lipid material containing cholesterol, cholesterol esters, triglycerides, diester waxes, and fatty acids. Sebum is important for keeping the skin soft and pliable and for maintaining proper hydration. Sebum gives the hair coat a sheen and has antimicrobial properties. There is some clinical evidence to suggest that limited sweating occurs in dogs and cats, and that it may have a minor role in cooling of the body. Dogs and cats thermoregulate primarily via panting, drooling, and spreading saliva on their coats (cats).

Common Manifestations Of Skin Disease: Overview Alopecia, dermatitis, and pruritus are all common manifestations of skin disease. Alopecia (Hair loss) Alopecia is the partial or complete lack of hairs in areas where they are normally present. Etiology: There are many causes of alopecia; any disease that can affect hair follicles can cause hair loss. There are two broad etiologic categories of alopecia—congenital or hereditary and acquired. Congenital or hereditary alopecia has been described in cows, horses, dogs, cats, and pigs. Hairless breeds of mice, rats, cats, and dogs have been bred and developed for personal and research interests. Congenital alopecia may or may not be hereditary; it is caused by a lack of development of hair follicles and is apparent at or shortly after birth. Acquired alopecia encompasses all of the other causes of hair loss. In this type of alopecia, the animal is born with a normal hair coat, has or had normal hair follicles at one time, and is/was capable of producing structurally normal hairs. Acquired alopecia can develop because the disease destroys the hair follicle or hair shaft, interferes with the growth of hair or wool, or causes the animal discomfort (eg, pain, pruritus) leading to self-trauma and loss of hair. Diseases that can directly cause destruction or damage to the hair shaft or follicle include bacterial skin diseases, dermatophytosis, demodicosis, severe inflammatory diseases of the dermis (eg, juvenile cellulitis, deep pyoderma), traumatic episodes (eg, burns, radiation), and (rarely) poisonings caused by mercury, thallium, and iodine. Diseases that can directly inhibit or slow hair follicle growth include nutritional deficiencies (particularly protein deficiencies), hypothyroidism, hyperadrenocorticism, and excessive estrogen production or administration (hyperestrogenism, Sertoli cell tumors, estrogen injections for mismating). Temporary alopecia in horses, sheep, and dogs can occur during pregnancy, lactation, or several weeks after a severe illness or fever. Pruritus or pain is a common cause of acquired alopecia in animals. Diseases that commonly cause pruritus or pain include infectious skin diseases (eg, bacterial pyoderma and dermatophytosis), ectoparasites, allergic skin diseases (eg, atopy, food allergy, contact, insect hypersensitivity), and less commonly neoplastic skin diseases. Clinical Findings and Lesions: Congenital or hereditary hair loss is commonly symmetrical and not accompanied by many inflammatory changes; in some cases, the areas of hair loss are localized to one region (eg, ear flaps) or to well-demarcated areas. The clinical signs of acquired hair loss are varied and often influenced by the underlying cause(s); the pattern of hair loss may be focal, multifocal, symmetrical, generalized, depending on the underlying cause(s). Inflammatory changes such as hyperpigmentation, lichenification, erythema, and pruritus are common. In endocrine alopecias, the hair loss usually develops in a symmetrical pattern, often in wear areas first; pruritus is uncommon unless there is a secondary infection. Hair loss is not generally an early clinical sign of an endocrine alopecia. Many owners seek veterinary assistance because of perceived excessive shedding. Shedding may be abnormal (excessive) if it results in obvious loss of the hair coat and areas of alopecia. A common cause of abnormal shedding is Merck Veterinary Manual - Summary

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bacterial pyoderma. If, however, the shedding is not accompanied by development of patchy or symmetrical hair loss, it is likely that it is just a stage in the natural replacement of the hair coat. Owners frequently do not recognize that the development and growth of a new hair is accompanied by the expulsion or shedding of the old hair. Diagnosis: On physical examination, the distribution of lesions should be noted (focal, multifocal, symmetrical, generalized), and the hairs examined to determine if they are being shed from the hair follicle or broken off—the latter suggesting pruritus. Signs of secondary skin infections or ectoparasites should be noted, and a careful nondermatologic examination should be performed. Initial diagnostic tests include skin scrapings for ectoparasites (particularly Demodex mites); combing of the hair coat for fleas, mites, and lice; impression smears of the skin, looking for evidence of bacterial or yeast infections; fungal cultures for identification of dermatophytosis; and examination of plucked hairs, looking at both the shaft and the ends for evidence of dermatophytosis or that the hairs were chewed off. If these tests do not identify or suggest an underlying cause, a skin biopsy may be indicated to evaluate hair follicle structures, numbers, and anagen/telogen ratios and to look for evidence of bacterial, fungal, or parasitic skin infections. Dermatitis The most common sign is scratching, followed by skin lesions that progress from edema and erythema to papules, vesicles, oozing, and crusting or scaling. Secondary infection may occur. As dermatitis becomes chronic, the erythema decreases and there are fewer papules, but the lesions are drier and the skin may develop fissures. Chronic dry dermatitis is usually helped by application of a corticosteroid ointment. To remove scales or crusts, a sulfur and salicylic acid or tar and sulfur shampoo may be used. Tar products are contraindicated in cats. Unfortunately, topical medications often are licked or rubbed off; systemic therapy with anti-inflammatory doses of corticosteroids is usually the best alternative. Restraining devices, such as hobbles or Elizabethan collars, and sedatives should be used only as last resorts in the therapy of pruritus. Pruritus (Itching) The nature of the mediators of pruritus is controversial but is believed to include both histamines (released from mast cell degranulation) and proteolytic enzymes (proteases). Proteases are released by fungi, bacteria, and mast cell degranulation, and during antigen-antibody reactions. Leukotrienes, prostaglandins, and thromboxane A2, which are broken down from arachidonic acid, are pro-inflammatory. Essential fatty acids, particularly γ-linolenic acid, have been used to counter the inflammation mediated by leukotrienes and thromboxane A2. Principles of Topical Therapy Shampoo Therapy: Shampoos are the most commonly used topical treatments. There are three broad classes of shampoos: cleansing, antiparasitic, and medicated. Cleansing shampoos remove dirt and excess oils from the coat. These products include overthe-counter dog grooming shampoos, flea shampoos, and many mild products for people. These products lather well and must be rinsed from the coat. Antiparasitic shampoos are “flea shampoos.” In most cases, the amount of insecticide in these products is not adequate to kill all of the fleas in a severe infestation. However, these products are excellent routine cleansing products. Medicated shampoos include antimicrobial and antiseborrheic products. The most widely used antimicrobial shampoos contain chlorhexidine or benzoyl peroxide. These products are antibacterial. Antifungal shampoos are best avoided because there is little evidence to suggest that the use of those products shorten the course of infection. Antiseborrheic shampoos contain some combination of tar, sulfur, and salicylic acid—ingredients that are keratoplastic and keratolytic. Tar is recommended for oily seborrhea, and sulfur and salicylic acid are recommended for scaly seborrhea. In reality, most animals benefit from products that contain all three agents. Allergic Inhalant Dermatitis: Introduction (Atopy) Allergic inhalant dermatitis is a very common allergy in dogs, second only to flea allergy in areas where fleas are present. It is a Type I hypersensitivity and affects ~10% of the canine population. Etiology and Pathogenesis: Animals with atopy are genetically programmed to become sensitized to allergens in the environment. Allergens are inhaled, absorbed through the skin and possibly the GI tract, and evoke allergen-specific IgE production. Allergen-specific IgG may also play a role in atopy. When allergen-specific IgE fixed to tissue mast cells comes in contact with the specific allergen, mast cell degranulation and release of proteolytic enzymes, histamine, bradykinins, and other vasoactive amines

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occurs and results in the inflammatory process. The skin is the primary target organ in dogs and cats, although rhinitis and asthma also occur in ~15% of these animals. Clinical Findings, Lesions, and Diagnosis: Pruritus is the characteristic sign of atopy. The feet, face, ears, axillae, and abdomen are the most frequently affected areas. Lesions develop secondary to self-trauma and include alopecia, erythema, scaling, salivary staining, serous and hemorrhagic crusting, excoriations, lichenification, and hyperpigmentation. Superficial staphylococcal pyoderma, otitis externa, and Malassezia dermatitis are common secondary complications. Differential diagnoses include food allergy, flea allergy, contact allergy, scabies, pyoderma, and Malassezia dermatitis. Treatment and Control: The three therapeutic options available for management of atopy are avoidance of the offending allergens, symptomatic therapy to help control pruritus, and immunotherapy (ie, hyposensitization, desensitization). Hyposensitization immunotherapy attempts to increase the ability of the animal to tolerate exposure to inhaled allergens without developing clinical signs. It should be the main form of therapy needed to control pruritus once the offending allergens have been accurately identified. Vaccine preparation involves selection of individual allergens, their concentrations, and preservatives. Most allergy vaccines are aqueous extracts. To maintain sterility, vaccines are preserved with either phenol or glycerin. Phenol-preserved vaccines lose potency faster than glycerinated vaccines, but glycerin-preserved vaccines can also cause local reactions in animals and have very limited use. Therefore, most vaccines are preserved with phenol (usually 0.4%). Vaccine concentrations are currently measured in protein nitrogen units (PNU) per mL or weight to volume (w/v). Neither method is an accurate measurement of biologic potency. By definition, 100,000 PNU is equal to 1 mg of protein. The w/v method measures the weight of defatted allergen, divided by the volume of diluent. Both methods are accepted, but the PNU measurement is generally preferred. Allergens are administered by SC injection. Oral administration is considered experimental and is less effective than via injection. The number of allergens in an individual allergy vaccine is limited. Currently, 10-18 allergens are commonly accepted as the maximum number. If too many allergens are used in one vaccine, the concentration of each individual allergen is low, and the response may not be adequate. Enough vaccine should be made up to last ~6 mo. Feline Atopy Feline atopy is similar to canine atopy, with several important distinctions. Feline atopy is a pruritic disease in which affected cats have a hypersensitivity reaction to inhaled environmental allergens and positive reactions to intradermal allergy testing. No studies have compared serologic testing with intradermal allergy testing for feline atopy. Clinical presentations include miliary dermatitis, feline symmetrical alopecia, eosinophilic granuloma complex (primarily the eosinophilic plaque), and severe head and neck pruritus. The pruritus and dermatologic lesions may be seasonal or year round. Response to steroids is excellent in most cases initially; however, efficacy decreases over time in most cases. Intradermal allergy testing and hyposensitization procedures are similar to those used in dogs, but the testing is more difficult to read because the reactions to intradermal injections of allergens are less dramatic in cats than in dogs. The hyposensitization response is similar to that seen in dogs. Food Allergy: Introduction Food allergy is ~10% as common as atopy in dogs and about as common as atopy in cats. The distribution of pruritus and lesions varies markedly between animals. Ear canal disease manifesting as pruritus and secondary infection with bacteria (usually Staphylococcus intermedius , Pseudomonas spp , Proteus spp , or Escherichia coli ) or yeast ( Malassezia pachydermatis ) are common and may be the only presenting complaint. Other patterns seen include blepharitis, generalized pruritus, generalized seborrhea, a papular eruption, or a distribution pattern that may mimic that of atopy (feet, face, and ventrum) or flea allergy dermatitis (dorsal lumbosacrum and hindlegs). The most common areas of involvement include the ears, feet, inguinal region, axillary area, proximal anterior forelegs, periorbital region, and muzzle. Food allergy remains a confusing allergy to diagnose because there is no reliable diagnostic test other than a strict food elimination diet. Serologic testing and intradermal testing for food allergens have proven unreliable. The ideal food elimination diet should be balanced and nutritionally complete and not contain any ingredients that have been fed previously to the animal. The key point in any food elimination diet trial is that only novel food ingredients can be fed. The trial diet should be fed for up to 3 mo. To confirm that a food allergy exists and that the clinical improvement was not just coincidental, the animal must be challenged with the previously fed food ingredients and a relapse of clinical signs must occur. The return of clinical signs after challenge is usually between 1 hr and 14 days, although it is usually within 3 days.

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The most frequently identified causative allergens in canine food allergy include beef, chicken, corn, wheat, soy, and milk. Once the offending allergens are identified, control of the food allergy is by strict avoidance of these offending allergens. Concurrent diseases (such as atopy or flea allergy) may complicate the identification of underlying food allergies. Clinical presentations of food allergy in cats include miliary dermatitis, feline symmetrical alopecia, eosinophilic granuloma complex (primarily the eosinophilic plaque), and severe head and neck pruritus. Response to steroids is variable, but about two-thirds of cats show excellent response to steroids initially. Cats should not be starved or forced into eating a new elimination diet due to the serious nature of hepatic lipidosis that may be induced by prolonged anorexia. Dermatophilosis: Introduction ( Dermatophilus infection, Cutaneous streptothrichosis, Lumpy wool, Strawberry footrot) The lesions are characterized by exudative dermatitis with scab formation. Dermatophilus congolensis has a wide host range. Among domestic animals, cattle, sheep, and goats are affected most frequently; horses occasionally; and pigs, dogs, and cats rarely. Etiology, Transmission, and Epidemiology: Dermatophilus congolensis is a gram-positive, non-acid-fast, facultative anaerobic actinomycete. It is the only species in the genus, but a variety of strains can be present within a group of animals during an outbreak. It has two characteristic morphologic forms—filamentous hyphae and motile zoospores. The hyphae are characterized by branching filaments (1-5 µm in diameter) that ultimately fragment by both transverse and longitudinal septation into packets of coccoid cells. The coccoid cells mature into flagellated ovoid zoospores (0.6-1 µm in diameter). The natural habitat of D congolensis is unknown. Attempts to isolate it from soil have been unsuccessful, although it is probably a saprophyte in the soil. It has been isolated only from the integument of various animals and is restricted to the living layers of the epidermis. Asymptomatic chronically infected animals are considered the primary reservoir. Epidemics usually occur during the rainy season. Moisture facilitates release of zoospores from preexisting lesions and their subsequent penetration of the epidermis and establishment of new foci of infection. High humidity also contributes indirectly to the spread of lesions by allowing increases in the number of biting insects, particularly flies and ticks, that act as mechanical vectors. Infection can be spread by shearing, dipping, or introducing an infected animal into a herd or flock. Dermatophilosis is contagious only in that any reduction in systemic or local skin resistance favors establishment of infection and subsequent disease. Pathogenesis: To establish infection, the infective zoospores must reach a skin site where the normal protective barriers are reduced or deficient. The respiratory efflux of low concentrations of carbon dioxide from the skin attracts the motile zoospores to susceptible areas on the skin surface. Zoospores germinate to produce hyphae, which penetrate into the living epidermis and subsequently spread in all directions from the initial focus. Hyphal penetration causes an acute inflammatory reaction. Natural resistance to the acute infection is due to phagocytosis of the infective zoospores, but once infection is established, there is little or no immunity. In most acute infections, the filamentous invasion of the epidermis ceases in 2-3 wk, and the lesions heal spontaneously. In chronic infections, the affected hair follicles and scabs are sites from which intermittent invasions of noninfected hair follicles and epidermis occur. The invaded epithelium cornifies and separates in the form of a scab. In wet scabs, moisture enhances the proliferation and release of zoospores from hyphae. The high carbon dioxide concentration produced by the dense population of zoospores accelerates their escape to the skin surface, thus completing the unique life cycle. Clinical Findings: Dermatophilosis occurs in animals at all ages but is most prevalent in the young. Lesions are not at the same stage of progression and, in an individual animal, can vary from acute to chronic. Variation also occurs because of age, sex, and breed. Few animals exhibit pruritus, and most recover spontaneously within 3 wk of the initial infection or during dry weather. Uncomplicated skin lesions heal without scar formation. These infections usually have little effect on general health. Animals with severe generalized infections often lose condition, and movement and prehension are difficult if the feet, lips, and muzzle are severely affected; these animals are often sent to slaughter as incurable. Deaths occasionally occur, particularly in calves and lambs, because of generalized disease with or without secondary bacterial infection and secondary fly or screwworm infestation. The primary economic consequences are damaged hides in cattle, wool loss in sheep, and lameness and loss of performance in horses when severely affected around the pastern area. Lesions: Distribution of the gross lesions on cattle, sheep, and horses usually correlates with the predisposing factors that reduce or permeate the natural barriers of the integument. In cattle, the lesions can be observed in three stages: 1) hairs matted together as “paintbrush” lesions, 2) crust or scab formation as the initial lesions coalesce, and 3) accumulations of cutaneous keratinized material forming “wart-like” lesions that are 0.5-2 cm in diameter. Typical lesions consist of circular, dome-shaped scabs 2-8 mm in diameter. Most lesions associated with prolonged wetting of the skin are distributed over the head, dorsal surfaces of the neck and body, and upper lateral surfaces of the neck and chest. Cattle that stand for long Merck Veterinary Manual - Summary

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periods in deep water and mud develop lesions in areas such as skin folds of the flexor surfaces of the joints. Lesions initiated by biting flies (mechanical vectors) are found primarily on the back, whereas lesions induced by ticks are primarily on the head, ears, axillae, groin, and scrotum. Chronic lumpy wool infections are characterized by pyramid-shaped masses of scab material bound to wool fibers. The crusts are primarily on the dorsal areas of the body and prevent the shearing of sheep; spiny plants often predispose to lesions on the lips, legs, and feet. Strawberry footrot is a proliferative dermatitis affecting the skin from the coronet to the carpus or hock. Lesions on horses with long winter hair coats are similar to those of cattle, developing with matted hair and “paintbrush” lesions leading to crust or scab formation with yellow-green pus present under larger scabs. With short summer hair, matting and scab formation is uncommon; loss of hair with a fine “paintbrush” effect can be extensive. Persistent wetting of pasterns in wet yards, stables, or at pasture leads to lower limb infection; white legs and the whiteskinned areas of the lips and nose are more severely affected. Generalized disease is also associated with prolonged wet weather. Outbreaks occur on farms with previously affected horses. Histopathologic examination of the lesions reveals the characteristic branching hyphae with multidimensional septations, coccoidal cells, and zoospores in the epidermis. The organisms are usually abundant in active lesions but can be sparse or absent in chronic lesions. Diagnosis: Differential diagnoses include dermatomycoses in most species, warts and lumpy skin disease in cattle, contagious ecthyma and ulcerative dermatosis in sheep, and dermatophytosis and immune-mediated scaling diseases of horses. Treatment and Control: Because acutely infected animals usually heal rapidly and spontaneously, treatment is indicated only for cosmetic reasons. Organisms are susceptible to a wide range of antimicrobials—erythromycin, spiramycin, penicillin G, ampicillin, chloramphenicol, streptomycin, amoxicillin, tetracyclines, and novobiocin. Usually, chronic infections can be rapidly and effectively cured with a single IM injection of procaine penicillin (22,000 IU/kg) and streptomycin (22 mg/kg Exudative Epidermitis: Introduction (Greasy pig disease) Exudative epidermitis is an acute, generalized dermatitis that occurs in 5- to 60-day-old pigs and is characterized by sudden onset, with morbidity of 10-90% and mortality of 5-90%. It has been reported from most swine-producing areas of the world. Lesions are caused by Staphylococcus hyicus (hyos) , but the bacteria seem unable to penetrate intact skin. Abrasions on the feet and legs or lacerations on the body precede infection. Such injuries are usually caused by fighting or by abrasive surfaces such as new concrete. Other predisposing factors include mange mites, a vesicular-type virus, or anything that damages the skin. Pigs develop resistance with age. Clinical Findings and Lesions: The first signs are listlessness and reddening of the skin in one or more piglets in the litter. Affected pigs rapidly become depressed and refuse to eat. Body temperature may be increased early in the disease but thereafter is near normal. The skin thickens, and reddish brown spots appear from which serum exudes. Usually, these are first seen behind the ears and on the lateral sides of the neck. The body is rapidly covered with a moist, greasy exudate of sebum and serum that becomes crusty. The accumulation of dirt gives the affected area a black color. Vesicles and ulcers also develop on the nasal disk and tongue. The feet are nearly always involved with erosions at the coronary band and heel; the hoof may be shed in rare cases. In the acute disease, death occurs within 3-5 days. In older animals, the disease is milder; circumscribed lesions develop slowly and do not coalesce. Mortality is low except in those affected while very young, but recovery is slow and growth is retarded. Necropsy of severely affected pigs reveals marked dehydration, congestion of the lungs, and inflammation of the peripheral lymph nodes. Treatment: The causative organism is inhibited by many antibiotics. Successful treatment requires that the antimicrobial be given in high dosages and for a period of 7-10 days. Success is greatest when antimicrobial therapy is combined with daily applications of antiseptics to the entire body surface. Treatment is less effective in very young pigs and ineffective in advanced cases. Pyoderma: Introduction Pyoderma is a pyogenic infection of the skin. Pyodermas are common in dogs but uncommon in cats. They are classified as primary or secondary, superficial or deep. Most skin infections are superficial and secondary to any of a variety of other conditions, most notably allergies (flea allergy, atopy, food allergy), internal diseases (particularly endocrinopathies Merck Veterinary Manual - Summary

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such as hypothyroidism or hyperadrenocorticism), seborrheic conditions (including follicular or sebaceous gland diseases), parasitic diseases (dermatophytes, Demodex canis , or anatomic predispositions [eg, skin folds]). Primary pyoderma occurs in otherwise healthy animals, without an identifiable predisposing cause, clears completely with appropriate antibiotics, and is usually due to Staphylococcus intermedius or other staphylococcal organisms. Etiology: Staphylococcus intermedius is the most common etiologic agent. Normal resident bacteria in canine skin include coagulase-negative staphylococci, streptococci, Micrococcus sp , and Acinetobacter sp . Transient bacteria in canine skin include Bacillus sp , Corynebacterium sp , Escherichia coli , Proteus mirabilis , and Pseudomonas sp . These organisms may play a role as secondary pathogens, but often Staphylococcus intermedius is required for a pathologic process to ensue. Normal resident bacteria in feline skin include Acinetobacter sp , Micrococcus sp , coagulase-negative staphylococci, and α-hemolytic streptococci. Transient bacteria in feline skin include Alcaligenes sp , Bacillus sp , Escherichia coli , Proteus mirabilis , Pseudomonas sp , coagulase-positive and coagulase-negative staphylococci, and βhemolytic streptococci. The most important factor in superficial pyodermas that allows a bacteria to colonize in the skin is bacterial adherence or "stickiness" to the keratinocytes. Warm, moist areas on the skin, such as lip folds, facial folds, neck folds, axillary areas, dorsal or plantar interdigital areas, vulvar folds, and tail folds, often have higher bacteria counts than other areas of skin and are at an increased risk for infection. Pressure points, such as elbows and hocks, are prone to infections, possibly due to follicular irritation and rupture due to chronic repeated pressure. Clinical Findings and Lesions: Shorthaired breeds often present with multiple superficial papules that look similar to urticaria because the inflammation in and around the follicles causes the hairs to stand more erect. These hairs are often easily epilated, an important feature that helps to distinguish superficial pyoderma from true urticaria. The hairs in the affected follicles epilate and progress to form focal areas of alopecia 0.5-2 cm in diameter. Pustules and crusts are infrequently found. When serous crusts are present, it is very likely that a secondary superficial pyoderma is also present. Feline superficial pyoderma is usually due to Staphylococcus intermedius , is uncommon, and usually presents with alopecia, papules, and focal crusting. Deep pyodermas in cats present with alopecia, ulcerations, hemorrhagic crusts, and draining tracts. They often indicate other systemic disease, such as feline immunodeficiency virus or feline leukemia virus, or atypical mycobacteria may be present. Diagnosis: Differential diagnoses for superficial pyoderma include demodicosis, Malassezia dermatitis, dermatophytosis, and other causes of folliculitis as well as uncommon crusting diseases such as pemphigus foliaceus. Multiple deep skin scrapings are needed to rule out parasitic infections, particularly Demodex canis . Dermatophyte culture is needed to rule out dermatophytosis. Bacterial culture and sensitivity testing is mandatory in cases of deep pyoderma and recurrent superficial pyoderma. Treatment: The primary treatment of superficial pyoderma is with appropriate antibiotics for ≥21 days. Appropriate antibiotic choice depends on bacterial culture and sensitivity test results. When cultures are not performed, good empirical antibiotic selections include cephalosorins, oxacillin, enrofloxacin, amoxicillin trihydrateclavulanic acid, and ormetoprim-sulfadimethoxine. Other antibiotics that are often helpful but may be less efficacious include lincomycin, clindamycin, erythromycin, trimethoprin-sulfamethoxazole, trimethoprim-sulfadiazine, and chloramphenicol. Amoxicillin, penicillin, and tetracyline are inappropriate choices for treating superficial or deep pyodermas because they are ineffective in 90% of these cases. Topical antibiotics may be helpful in focal superficial pyoderma. A 2% mupiricin ointment penetrates skin well and is helpful in deep pyoderma, is not systemically absorbed, has no known contact sensitization, and is not used as a systemic antibiotic that would increase the likelihood of cross-resistance. It is not very effective against gram-negative bacteria. Neomycin is more likely to cause a contact allergy than other topicals and has variable efficacy against gram-negative bacteria. Bacitracin and polymyxin B are more effective against gram-negative bacteria than other topical antibiotics but are inactivated in purulent exudates. In addition to antibiotic therapy, shampoo therapy (see seborrhea , Seborrhea: Introduction) will help remove bacteria, crusts, and scales, as well as reduce the pruritus, odor, and oiliness associated with the pyoderma. Early in the course of therapy of a deep pyoderma, gentle warm water soaks or hydrotherapy are safe, painless, and soothing. They improve blood flow to the affected areas and minimize aggravation of the lesions, which allows for healing with less formation of scar tissue. Contagious Ecthyma: Introduction (Orf, Contagious pustular dermatitis, Sore mouth) Contagious ecthyma is an infectious dermatitis of sheep and goats that affects primarily the lips of young animals. 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Etiology and Epidemiology: The causal poxvirus (a parapoxvirus) is related to those of pseudocowpox and bovine papular stomatitis. Infection occurs by contact. The virus is highly resistant to desiccation, having been recovered from dried crusts after 12 yr. It is also resistant to glycerol and to ether. Contagious ecthyma is found worldwide and is most common in late summer, fall, and winter on pasture, and in winter in feedlots. Clinical Findings and Diagnosis: Ewes nursing infected lambs may develop lesions on the udder. In young lambs, the initial lesion may develop on the gum below the incisor teeth. The lesions develop as papules and progress through vesicular and pustular stages before encrusting. When the lesion extends to the oral mucosa, secondary necrobacillosis ( Calf Diphtheria) frequently develops. During the course of the disease (1-4 wk), the scabs drop off and the tissues heal without scarring. During active stages of the infection, the more severely affected lambs fail to eat normally and lose condition. Extensive lesions on the feet lead to lameness. Mastitis may result in ewes with lesions on the udder. The lesion is characteristic. The disease must be differentiated from ulcerative dermatosis ( Ulcerative Dermatosis Of Sheep: Introduction), which produces tissue destruction and crateriform ulcers. Ecthyma usually affects younger animals than does ulcerative dermatosis, although this criterion can only be used presumptively. Treatment and Control: Antibacterials may help combat secondary infection. The virus is transmissible to man, and the lesions, usually confined to the hands and face, are more proliferative and occasionally very distressing. Sheep that have recovered from natural infection are highly resistant to reinfection. Sheep immunized against contagious ecthyma remain susceptible to ulcerative dermatosis. Dermatophytosis: Introduction (Ringworm) Dermatophytosis is an infection of keratinized tissue (skin, hair, and claws) by one of the three genera of fungi collectively called dermatophytes— Epidermophyton , Microsporum , and Trichophyton . (See also fungal infections , Fungal Infections: Introduction). In developed countries, the greatest economic and human health consequences come from dermatophytosis of domestic cats and cattle. The most important animal pathogens worldwide are M canis , M gypseum , T mentagrophytes , T equinum , T verrucosum , and M nanum . These species can be spread to and cause ringworm in people, especially M canis infections of domestic cats and T verrucosum of cattle and lambs. Under most circumstances, dermatophytes grow only in keratinized tissue, and advancing infection stops on reaching living cells or inflamed tissue. Infection begins in a growing hair or in the stratum corneum, where threadlike hyphae develop from the infective arthrospores or fungal hyphal elements. Hyphae can penetrate the hair shaft and weaken it, which together with follicular inflammation, leads to patchy hair loss. As the infection matures, clusters of arthrospores develop on the outer surface of infected hair shafts. Broken hairs with associated spores are important sources for spread of the disease. In young or debilitated animals and, to some extent, in longhaired breeds of domestic cats, infection may be persistent and widespread. Dermatophytosis is diagnosed by fungal culture, examination with a Wood's lamp, and direct microscopical examination of hair or skin scale. Fungal culture is the most accurate means of diagnosis. Dermatophyte test medium (DTM) may be used in a clinical setting. The Wood's lamp is useful in screening examinations for M canis infections in cats and dogs. Infected hairs fluoresce yellow-green; however, only 80% of M canis infections fluoresce, and other fungal species in animals do not. Therefore, negative Wood's lamp examinations are not meaningful. False-positive examinations may occur and are especially likely in oily, seborrheic skin conditions. Fluorescing hairs should always be cultured to confirm the diagnosis. Dogs and Cats In dogs, ~70% of cases are caused by Microsporum canis , 20% by M gypseum , and 10% by Trichophyton mentagrophytes ; in cats, 98% are caused by M canis . Definitive diagnosis is established by DTM culture. Occasionally, dermatophytosis in cats causes feline miliary dermatitis and is pruritic. Cats with generalized dermatophytosis occasionally develop cutaneous ulcerated nodules, known as pseudomycetomas. Dermatophytosis in dogs and shorthaired cats is usually self-limiting, but resolution can be hastened by treatment. Another primary objective of therapy is to prevent spread of infection to other animals and people. Dogs can be treated with the microsized formulation of griseofulvin at 25-100 mg/kg body wt given once daily or divided, with a fat-containing meal, and cats with 25-50 mg/kg daily in divided doses. These dosages are higher than those approved by the FDA. Cats may develop bone marrow suppression, especially neutropenia, at higher doses or as idiosyncratic reactions. In both dogs and cats, GI upset is a fairly common sequela of griseofulvin administration. Alternative and effective treatments include ketoconazole at 10 mg/kg or itraconazole at 5 mg/kg, daily, but neither of these drugs is approved for use in domestic Merck Veterinary Manual - Summary

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animals. Systemic and topical treatments for dermatophytosis should be continued for 2-4 wk past clinical cure or until a negative brush culture is obtained. This A killed fungal cell wall vaccine has recently been approved for treatment and prevention of M canis ringworm in cats. Cuterebra Infestation in Small Animals: Introduction This opportunistic, parasitic infestation of dogs and cats is caused by the rodent or rabbit botfly, Cuterebra spp (order Diptera, family Cuterebridae). Flies are usually host- and site-specific relative to their life cycle. However, rabbit Cuterebra are less host-specific and are usually associated with dog and cat infestations. Rarely, cats and dogs may be infested with Hypoderma spp or Dermatobia hominis . Etiology: Adult Cuterebra flies are large and bee-like and do not feed or bite. Females deposit eggs around the openings of animal nests, burrows, along runways of the normal hosts, or on stones or vegetation in these areas. A female fly may deposit 5-15 eggs per site and >2,000 eggs in her lifetime. Animals become infested as they pass through contaminated areas; the eggs hatch in response to heat from a nearby host. In the target host, the larvae enter the body through the mouth or nares during grooming or, less commonly, through open wounds. After penetration, the larvae migrate to various speciesspecific subcutaneous locations on the body, where they develop and communicate with the air through a breathing pore. After ~30 days, the larvae exit the skin, fall to the soil, and pupate. The duration of the pupation varies depending on the environmental factors and winter diapause. Clinical Findings and Diagnosis: Cuterebra lesions are most common in the summer and fall when the larvae enlarge and produce a fistulous swelling ≥1 cm in diameter. Dogs and cats are abnormal hosts for this parasite; aberrant migrations can involve the head, brain, nasal passages, pharynx, and eyelids. In the skin, typical lesions are seen around the head, neck, and trunk. The hair is often matted, and a subcutaneous swelling is present beneath the lesions. Cats often groom the area aggressively. Pain at the site is variable and usually associated with secondary infections. Purulent material may exude from the lesion; the most common differential diagnosis is an abscess or foreign body. Definitive diagnosis is made by finding and identifying a larva. Treatment: Suspect lesions should be explored by carefully enlarging and probing the breathing pore or fistula. The lesion should not be squeezed because this may rupture the larva and lead to a chronic foreign body reaction and secondary infection. There are anecdotal reports of larval rupture causing anaphylaxis. If possible, the larva should be removed in one piece; recurrent abscesses at the site of previous Cuterebra suggest residual infection or remaining pieces of larva. The area should be thoroughly flushed with sterile saline, debrided (if necessary), and allowed to heal by granulation. Fleas and Flea Allergy Dermatitis: Introduction Fleas are complete metamorphic insects, having developmental stages consisting of eggs, larvae, pupae, and adults. In North America, only a few species commonly infest dogs and cats: Ctenocephalides felis (the cat flea), C canis (the dog flea), Pulex simulans (a flea of small mammals), and Echidnophaga gallinacea (the poultry sticktight flea). However, by far the most prevalent flea on dogs and cats is C felis . The cat flea is the cause of severe irritation in animals and man and is responsible for flea allergy dermatitis. It also serves as the vector of typhus-like rickettsiae and is the intermediate host for filarid and cestode parasites. Transmission, Epidemiology, and Pathogenesis: Cat fleas deposit their eggs in the pelage of their host. The eggs are pearly white, oval with rounded ends, and 0.5 mm long. They readily fall from the pelage and drop onto bedding, carpet, or soil, where hatching occurs in ~1-6 days. Newly hatched flea larvae are 2-5 mm long, slender, white, segmented, and sparsely covered with short hairs. Larvae are freeliving, feeding on organic debris found in their environment and on adult flea feces, which are essential for successful development. Flea larvae avoid direct light and actively move deep in carpet fibers or under organic debris (grass, branches, leaves, or soil). Larvae are susceptible to desiccation, with exposures to relative humidity 100 days. The cat flea is susceptible to cold. No stage of the life cycle (egg, larva, pupa, or adult) can survive exposure to 5,000 ft) tend to inhibit flea development. When feeding, fleas inject saliva that contains proteolytic enzymes and histamine-like substances, resulting in irritation and pruritus, and substances that are responsible for the production of hypersensitivity. Flea saliva contains haptens of low molecular weight and at least two additional allergens with molecular weights >20,000 daltons. Flea-naive dogs exposed intermittently to flea bites develop either immediate (15 min) or delayed (24-48 hr) reactions, or both, and detectable levels of both circulating IgE and IgG antiflea antibodies. Dogs exposed continuously to flea bites have low levels of these circulating antibodies and either do not develop skin reactions or develop them later and to a considerably reduced degree. This could indicate that immunologic tolerance may be developed naturally in dogs continuously exposed to flea bites. Although the pathophysiology of FAD in cats is poorly understood, similar mechanisms may exist. Clinical Findings: The nonallergic animal may have few clinical signs other than occasional scratching due to annoyance of flea bites. Those that are allergic will typically have a dermatitis that is characterized by pruritus. In dogs, the pruritus associated with FAD can be intense and may manifest over the entire body. “Classic” clinical signs are papulocrustous lesions distributed on the lower back, tailhead, and posterior and inner thighs. Dogs may be particularly sensitive in the flanks, caudal and medial thighs, ventral abdomen, lower back, neck, and ears. Affected dogs are likely to be restless and uncomfortable, spending much time scratching, licking, rubbing, chewing, and even nibbling at the skin. Hair may be stained brown from the licking and is often broken off. Common secondary lesions include areas of alopecia, erythema, hyperpigmented skin, scaling, papules, and broken papules covered with reddish brown crusts. As FAD progresses, damage to the epidermis and hair follicles may result in a secondary pyoderma and seborrhea. In extremely hypersensitive dogs, extensive areas of alopecia, erythema, and self-trauma are evident. Traumatic moist dermatitis (“hot spots”) can also occur. As the disease becomes chronic, the dog may develop generalized alopecia, severe seborrhea, hyperkeratosis, and hyperpigmentation. The primary dermatitis is a papule, which often becomes crusted. This “miliary” dermatitis is typically found on the back, neck, and face. The miliary lesions are not actual flea bites but a manifestation of a systemic allergic reaction that leads to generalized pruritus and an eczematous rash. Pruritus may be severe, evidenced by repeated licking, scratching, and chewing. Cats with FAD can have alopecia, facial dermatitis, exfoliative dermatitis, and “racing stripe” or dorsal dermatitis. Diagnosis: Most cases occur in the late summer, corresponding to the peak of flea populations. In these cases, history can be highly suggestive. Age of onset is also important because FAD does not ordinarily occur before 1 yr of age. Usually, diagnosis is made by visual observation of fleas on the infested pet. Demonstration to the owner of the presence of fleas or flea excrement is helpful. Slowly parting the hair against the normal lay often reveals flea excrement or the rapidly moving fleas. Flea excrement is reddish black, cylindrical, and pellet- or comma-shaped. Placed in water or on a damp paper towel and crushed, the excrement dissolves, producing a reddish brown color. The extremely hypersensitive animal is likely to be virtually free of fleas due to excessive grooming behavior. In these cases, it is usually difficult to find evidence of fleas, thus making it more difficult to convince the owner of the

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problem. Use of a fine-toothed flea comb (32 teeth/inch) facilitates finding of fleas and their excrement. Examination of the pet's bedding for eggs, larvae, and excrement is also useful. The presence of fleas or a positive reaction to an intradermal test does not rule out the presence of another dermatologic disease responsible for the clinical signs. In dogs, differential diagnoses include allergic inhalant dermatitis (atopy), food allergy dermatitis, sarcoptic or demodectic mange, other ectoparasites, and bacterial folliculitis. In cats, other conditions that can result in miliary dermatitis include external parasites (cheyletiellosis, trombiculosis, notoedric mange, and pediculosis), dermatophytosis, drug hypersensitivity, food allergy, atopy, bacterial folliculitis, and idiopathic miliary dermatitis. Treatment and Control: Flea infestations in the home may be controlled effectively by using an insecticide with residual activity (or by repeated application of short-acting insecticides) in combination with an insect growth regulator (IGR). IGR are compounds that inhibit the development of immature stages of insects. They are generally classified as either juvenile hormone analogs (eg, methoprene and fenoxycarb) or chitin synthesis inhibitors (also called insect development inhibitors [eg, lufenuron]). These compounds prevent the development of flea eggs and larvae. IGR can be used alone or in combination with insecticides in a variety of formulations. Methoprene and fenoxycarb can be applied either to the environment or topically. Lufenuron is administered orally to the pet once monthly. The density of the carpet may affect the penetration of insecticide into the flea microenvironment. Flea larvae escape most traditional insecticide treatments because the treatment fails to contact them at the base of carpet fibers where they develop. In addition, ~2.5 times more insecticide per gram of body weight is required to kill larvae than to kill adults. However, IGR effectively inhibit larval development in carpeting. Borate-based carpet powders also offer considerable larvicidal activity. Insecticides and IGR in the home can be applied by broadcast treatment or through the use of total release aerosols or “foggers.” Broadcast treatment is done using either hand pump sprayers or pressurized aerosols. During application, the surface of all rugs and carpets must be treated adequately. In severe infestations, a second treatment may be necessary 1-3 wk later due to continued emergence of adult fleas from cocoons hidden deep within carpets. Flea pupae present a major problem in control programs. When an insecticidal formulation containing an IGR is applied, most (if not all) of the resident adult fleas are killed and further larval development is stopped; however, pupae will continue to develop and adult fleas will continue to emerge from cocoons for the next 2-4 wk. Because most residual insecticides take several hours to kill adult fleas, these emerging fleas may reinfest the pet or bite the owner before succumbing to the insecticide. Elimination of fleas in the yard can be an important aspect of flea control. such as dog houses, within garages, under porches, and in animal lounging areas beneath shrubs or other shaded areas. Entomopathogenic nematodes that parasitize flea larvae and pupae also can be used in these areas to inhibit the buildup of the flea population. Spraying flea control products over the large expanse of a shade-free lawn generally is not beneficial. Various insecticides, including organophosphates, carbamates, pyrethrins, and pyrethroids, are used in sprays, dips, squeeze-on liquids for spot treatment. Some topical formulations now have both adulticidal and IGR activities. The insecticide results in “knockdown” of existing fleas, while the IGR provides residual ovicidal activity to interrupt the development of flea eggs deposited in the hair coat. Use of a methoprene-containing “egg collar” or orally administered lufenuron prevents fleas from producing viable eggs. When used early in a flea season or before fleas are present, these compounds prevent the buildup of flea populations. Despite the efforts of pet owners, the total elimination of fleas is occasionally not feasible. Supportive medical therapy must be instituted to control pruritus and secondary skin disease in the hypersensitive animal. Systemic glucocorticosteroid therapy is often needed to control inflammation and associated pruritus. Short-acting prednisone or prednisolone can be administered initially at a dosage of 0.5-1.0 mg/kg daily, tapering the dosage and using alternate-day therapy until the lowest dose possible that still controls the pruritus is given. As soon as flea control is accomplished, the glucocorticosteroid can be discontinued. Anti-inflammatory therapy should never be used as a substitute for flea control. Cutaneous Habronemiasis (Summer sores, Jack sores, Bursatti) Cutaneous habronemiasis is a skin disease of Equidae caused in part by the larvae of the spirurid stomach worms ( Habronema spp). When the larvae emerge from flies feeding on preexisting wounds or on moisture of the genitalia or eye, they migrate into and irritate the tissue, which causes a granulomatous reaction. The lesion becomes chronic, and healing is protracted. Diagnosis is based on finding nonhealing, reddish brown, greasy skin granulomas that contain, yellow, calcified material the size of rice grains. Larvae, recognized by spiny knobs on their tails, can sometimes be demonstrated in scrapings of the lesions. Many different treatments have been used, most with poor results. Symptomatic treatment, including use of insect repellents, may be of benefit, and organophosphates applied topically to the abraded surface may kill the larvae. Surgical removal or cauterization of the excessive granulation tissue may be necessary. Treatment with ivermectin (200 µg/kg) has been effective, and although Merck Veterinary Manual - Summary

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there may be temporary exacerbation of the lesions (presumably in reaction to the dying larvae), spontaneous healing may be expected. Control of the fly hosts and regular collection and stacking of manure, together with anthelmintic therapy with ivermectin, may help to reduce the incidence. Lice: Introduction (Pediculosis) Various species of biting or chewing lice (order Mallophaga) and sucking lice (order Anoplura) infest domestic animals. Sucking lice infest mammals only, but biting lice infest both mammals and birds (see also ectoparasites of poultry, Bedbugs , Examination for Ectoparasites , Ectoparasites ). Etiology: Lice are wingless, flattened insects, usually 2-4 mm long. The claws of the legs are adapted for clinging to hairs and feathers. Anoplura are blood feeders. The three mouthpart stylets are retracted within the head when not in use. Mallophaga have ventral chewing mandibles and live on epidermal products; some species feed on blood and exudates when available. Louse eggs or "nits" are glued to hairs and are pale, translucent, and suboval. Nymphal lice (three stages) are smaller than adults but otherwise resemble them in habits and appearance. About 3-4 wk are required to complete one generation, but this varies with species. Clinical Findings and Diagnosis: Extreme infestation with sucking lice can cause anemia. Sucking lice cause small wounds that may become infected. The constant crawling and piercing or biting of the skin causes nervousness in hosts. Diagnosis should be based on the presence of lice. The hair should be parted, and the skin and proximal portion of the coat examined with the aid of light if indoors. On small animals, the ova are readily seen. Occasionally, when the coat is matted, the lice can be seen when the mass is broken apart. Biting lice are active and can be seen moving through the hair. Sucking lice usually move more slowly and are often found with mouthparts embedded in the skin. Pediculosis of livestock is most prevalent during the winter; severity is greatly reduced with the approach of summer. Infestations, particularly of sucking lice, may become severe. Transmission usually occurs by host contact. Treatment: Louse control usually requires treatment with an effective insecticide or drug. Both dipping and thorough spraying with an insecticide provide excellent coverage of animals, and usually two treatments 2 wk apart effectively control lice. Dipping consistently provides the most thorough coverage, but the number of formulations that can be applied by this method is limited. Examples of formulations that may be applied via dipping include phosmet, which is approved for beef cattle, and coumaphos, which may be applied as a dip to beef cattle, nonlactating dairy cattle, sheep, and goats. Many compounds are effective when applied as a whole body spray for lice control. A light, mist application of some formulations may be effective, while others may require soaking the hair to the skin. As much as 12 L may be required on large, long-haired cattle. Zero to very low residue tolerances for pesticides in milk limit the insecticides that may be applied to dairy cattle and dairy goats. Permethrin spray may be applied to these animals for control of lice. Additionally, dairy cattle may be sprayed with permethrin synergized with piperonyl butoxide, coumaphos, tetrachlorvinphos plus dichlorvos, and amitraz. In lactating dairy cattle, the appropriate milk withdrawal time must be observed. Because of ease of application and reduced stress to the treated animal, the pour-on method has become a popular means of applying a variety of products. Beef cattle, lactating dairy cattle, sheep, and nonlactating goats may be treated with pour-on formulations of permethrin for louse control. The paste formulation of famphur is approved for control of both biting and sucking lice. Ivermectin, injectable and premix, is effective against the sucking louse of swine. Dogs can be treated with dips, washes, sprays, or dusts. Effective compounds include permethrin, pyrethrins, rotenone, methoxychlor, lindane, diazinon, malathion, or coumaphos. Doses of ivermectin high enough to be effective for lice are not recommended in dogs. On cats, only carbaryl, rotenone, or pyrethrins should be used. Mange in Dogs and Cats Sarcoptic Mange (Canine Scabies): Sarcoptes scabiei canis infestation is a highly contagious disease of dogs found worldwide. The mites are fairly hostspecific, but animals (including man) that come in contact with infested dogs can also be affected. The adult mite is roughly circular in shape, without a distinctive head, and has four pairs of short legs. Females are almost twice as large as males. The entire life cycle (17-21 days) is spent on the dog, where the female burrows tunnels in the stratum corneum and lays her eggs. Sarcoptic mange is readily transmitted between dogs by direct contact. The incubation period is variable (10 days to 8 wk) and depends on level of exposure, body site, and number of mites transmitted. Asymptomatic carriers may exist. Intense pruritus is characteristic and is probably Merck Veterinary Manual - Summary

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due to hypersensitivity to mite products. Primary lesions consist of a papular eruption that, due to self-trauma, develops thick crusts with secondary bacterial infection. Typically, lesions start on the ventral abdomen, chest, ears, elbows, and legs and, if untreated, become generalized. Dogs with chronic, generalized disease develop severe thickening of the skin with fold formation and crust buildup, peripheral lymphadenopathy, and emaciation; dogs so affected may even die. "Scabies incognito" has been described in well-groomed dogs; these dogs, infested with sarcoptic mites, are pruritic, but demonstrating the mites on skin scrapings is difficult because the crust and scale have been removed by regular bathing. Diagnosis of sarcoptic mange is based on the history of severe pruritus of sudden onset, possible exposure, and involvement of other animals, including man. Sometimes, making a definitive diagnosis is difficult because of negative skin scrapings. Concentration and flotation of several scrapings may increase chances of finding the mites. Several extensive superficial scrapings should be done of the ears, elbows, and hocks; nonexcoriated areas should be chosen. Fecal flotation may reveal mites or eggs. Even if mites are not found but the history and clinical presentation are highly suggestive of sarcoptic mange, trial therapy is warranted. The hair should be clipped, the crusts and dirt removed by soaking with a good antiseborrheic shampoo, and an acaricidal dip applied. Lime-sulfur is highly effective and safe for use in young animals; several dips 5 days apart are recommended. Phosmet has been successfully used according to label instructions. Amitraz is an effective scabicide, although it is not approved for this use, and there have been some reports of lack of efficacy. Ivermectin is not approved for this use, but 200 µg/kg, PO or SC, two treatments 2 wk apart, is very effective and usually curative. Ivermectin at this dosage is contraindicated in Collies and Collie crosses, and the heartworm status of the dog should be evaluated before treatment. Notoedric Mange (Feline Scabies): This rare, highly contagious disease of cats and kittens is caused by Notoedres cati , which can opportunistically infest other animals, including man. The mite and its life cycle are similar to the sarcoptic mite. Pruritus is severe. Crusts and alopecia are seen, particularly on the ears, head, and neck, and can become generalized. Mites can be found in skin scrapings. Treatment consists of lime-sulfur dips at 10-day intervals. Nonapproved treatments include amitraz at half the concentration used in dogs and ivermectin at 200 µg/kg, SC. Sudden death in association with the use of ivermectin in kittens has been reported. Cheyletiellosis (Walking Dandruff): Cheyletiella blakei infests cats, C yasguri infests dogs, and C parasitovorax infests rabbits, although cross-infestations are common, including human infestation. This disease is very contagious. Mite infestations are rare in flea endemic areas, probably due to the regular use of insecticides. These mites have four pairs of legs and prominent hook-like mouthparts. They live on the surface of the epidermis, and their entire life cycle (3 wk) is spent on the host. Cats may develop dorsal crusting or generalized miliary dermatitis. Asymptomatic carriers may exist. The mites may not be easy to find, especially in animals that are bathed often; acetate tape preparations, superficial skin scrapings, and flea combing can be used to make the diagnosis. Weekly dippings with pyrethrins or lime-sulfur for 6-8 wk are necessary to eradicate the mites. Ivermectin is also an effective, but nonapproved, treatment. The environment should also be treated with a good insecticide. Canine Demodicosis: This common skin disease of dogs occurs when large numbers of Demodex canis mites inhabit hair follicles, sebaceous glands, or apocrine sweat glands. In small numbers, these mites are part of the normal flora of the skin of dogs and cause no clinical disease. The mites are transmitted from dam to puppies during nursing within the first 72 hr after birth. The mites spend their entire life cycle on the host, and the disease is not considered to be contagious. The pathogenesis of demodicosis is complex and not completely understood; evidence of hereditary predisposition for generalized disease is strong. Immunosuppression, natural or iatrogenic, can precipitate the disease in some cases. Other factors known to predispose to generalized demodicosis include systemic disease, estrus, and heartworm infection. Two clinical forms of the disease exist. Localized demodicosis occurs in dogs 45° at the toe. Dairy cows should have their claws trimmed at least once each year. If the incidence of lameness in the herd is considered higher than normal, twice yearly claw trimming is recommended. It is preferable for claw trimming to be done when cows are not heavily pregnant or during peak lactation. Footbaths Routine use of a footbath can reduce the incidence of lameness by up to 10%. If footrot (interdigital phlegmon) is a major herd problem, there has been some success with using footbaths on a regular basis. For digital dermatitis, an antibiotic footbath is often used for treatment. Many types of footbaths are used, including those containing formalin, copper and zinc sulfate (which are more expensive and slightly less effective than formalin), and antibiotics. Formalin (3-5%) is the least expensive footbath solution; it lasts longer in the bath than other products and has good bacteriostatic activity as well as having some potential for hardening the epidermis. However, the fumes from formalin are an irritant and, under certain conditions, milk can be tainted. In many areas, local laws prohibit the use of formalin. Formalin is also ineffective at temperatures 90% of S agalactiae infections. Streptococcus uberis , S dysgalactiae , and other environmental streptococci pose threats of mastitis infections on most farms. These infections arise from environmental exposure of the teat after milking and from contamination of teat skin between milkings. Most environmental streptococcal infections last 14-30 days. Subclinical mastitis caused by environmental streptococci may result in high somatic cell counts on individual cows for short periods (≤30 days). Coliform Mastitis: The most common coliforms are Escherichia coli , Enterobacter aerogenes , and Klebsiella spp . In quarters with low cell counts, coliforms multiply rapidly. The inflammatory reaction that follows destroys the coliform population, thereby releasing endotoxin. The resulting toxemia produces the local and systemic signs of acute or peracute mastitis (including gangrene in occasional cases), and death may occur. Rectal temperature in acute or peracute mastitis is 103-108°F (3942°C). Milk secretion ceases (even though usually only one gland is infected), and anorexia, depression, dehydration, and Merck Veterinary Manual - Summary

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rapid weight loss are prominent. The secretion of the clinically affected quarter(s) is usually brownish and watery. Diarrhea also may occur. A unique feature is that, on recovery, the udder tissue may return to normal so that, in a subsequent lactation, no fibrosis is found and the gland can produce to full potential. Cows producing milk with low WBC counts (24 hr after parturition. Occasionally, the membranes may be within the uterus and not readily apparent, in which case their presence may be detected by a foul-smelling discharge. In most cases, there are no signs of systemic illness. When systemic signs are seen, they are related to toxemia. However, such cows are at increased risk of developing metritis, ketosis, mastitis, and even abortion in a subsequent pregnancy. Cows that have once had retained fetal membranes are at increased risk of developing the condition at a subsequent parturition. Manual removal of the retained membranes is no longer recommended and is potentially harmful. Trimming of excess tissue that is objectionable to animal handlers and contributes to gross contamination of the genital tract is permissible. Untreated cows expel the membranes in 2-11 days. Routine use of intrauterine antimicrobials has not been found to be beneficial and may be detrimental. Although oxytocin, estradiol, and prostaglandin F2α have all been advocated at various

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times, none hastens expulsion of retained membranes. When signs of systemic illness are present, systemic treatment with antimicrobials and nonsteroidal anti-inflammatory drugs is indicated. Mares: The equine fetal membranes are normally expelled within 3 hr after parturition, but expulsion may be delayed for 8-12 hr or even longer without signs of illness. Retention of fetal membranes may mediate development of metritis or even peritonitis. Laminitis is a potential sequela. In cases of prolonged retention of fetal membranes, antimicrobials should be administered prophylactically along with nonsteroidal anti-inflammatory drugs and other therapeutic strategies to prevent laminitis. Sheep, Goats, and Pigs: In sows, retained placentas are contained within the uterus and are not visible at the vulva. In this species, entire fetuses may be retained. Usually, the fetus or membranes decomposes in situ, which may be accompanied by signs of systemic illness and a purulent vaginal discharge. Although serious or fatal sequelae occasionally occur, the prognosis for recovery and future fertility is surprisingly good. Oxytocin and antimicrobial treatment are indicated. Trichomoniasis: Introduction Trichomoniasis is a venereal protozoal disease of cattle characterized primarily by early fetal death and infertility, resulting in extended calving intervals. Distribution is probably worldwide. Etiology and Epidemiology: The causative protozoan, Trichomonas (Tritrichomonas) foetus , is pyriform and ordinarily 10-15 × 5-10 µm, but there is considerable pleomorphism. Although T foetus can survive the process used for freezing semen, it is killed by drying or high temperatures. Trichomonas foetus is found in the genital tracts of cattle. When cows are bred naturally by an infected bull, 30-90% become infected. By contrast, most cows are free of infection within 3 mo after breeding. However, immunity is not longlasting and reinfection does occur. Transmission can also occur when the semen from infected bulls is used for artificial insemination. Clinical Findings: Trichomonas foetus has been found in vaginal cultures taken as late as 8 mo of gestation and, apparently, live calves can be born to infected dams. Pyometra occasionally develops after breeding. Diagnosis: History and clinical signs are useful but are essentially the same as those of campylobacteriosis. Douching with saline or lactated Ringer's solution (without preservatives) can be used. Studies suggest that 90-95% of infected bulls will be positive on culture, and that three successive cultures at weekly intervals will detect ~99.5% of infected bulls. Vaginal pus (after treatment of pyometra) or vaginal mucus (obtained toward the end of a luteal phase) may also be of diagnostic value. Treatment and Control: Various imidazoles have been used to treat bulls, but none is both safe and effective. Ipronidazole is probably most effective but, due to its low pH, frequently causes sterile abscesses at injection sites. Trichomonas foetus can be safely eliminated from semen with dimetridazole. Vaccines have been developed for use in cows but none is highly effective. Bovine Ulcerative Mammillitis (Bovine herpes mammillitis) Bovine ulcerative mammillitis is a severe, ulcerative condition of the teats of dairy cows that can occur in outbreaks and result in marked loss of milk production as well as high incidence of secondary mastitis. It was initially reported in the UK but also occurs in the USA and other countries. It is caused by bovine herpesvirus 2. The lesions begin as one or more thickened plaques of varying size on the skin of one or more teats. Vesiculation of these plaques occurs quickly, and the surface sloughs, leaving a raw, ulcerated area that becomes covered with a blackbrown scab. The scabs tend to crack and bleed, especially if milking is attempted. Much of the teat wall may be involved, and often the lesion includes the teat orifice, which predisposes to mastitis and obstruction of the streak canal. In the early stages, before vesiculation is marked, intranuclear inclusions may be detected in the cells of the epidermis. The disease is more severe in first-lactation cows that have recently calved, especially those with udder edema. Severe lesions may take several weeks to heal. Diagnosis is based on the signs and confirmed by histopathology or by virus isolation from early lesions. Virus neutralization titers rise quickly, and the first serum sample must be taken early in the course of disease. Affected cows should be isolated, and separate milking utensils used. Cannulas may be necessary to remove milk. Emollient antiseptic ointments used after milking may reduce further trauma, hemorrhage, and secondary bacterial infections. Prophylactic infusions for mastitis should be considered if the teat orifice is involved. Iodophor teat dip solutions (10,000 ppm) may be useful as teat and udder disinfectants to aid control in infected herds. Premilking heifers that have Merck Veterinary Manual - Summary

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udder edema may improve blood flow and reduce the chance of mammillitis. Diuretics can be used to control edema. Milking susceptible cows first will reduce the chance of exposure from milking older cows, which may harbor the virus and contaminate the milking machine liner. Uterine Prolapse And Eversion: Introduction Prolapse of the uterus may occur in any species; however, it is most common in dairy cows and ewes and less frequent in sows. (It is rare in mares, bitches, queens, and rabbits.) The etiology is unclear and occurrence is sporadic. Recumbency with the hindquarters lower than the forequarters, invagination of the tip of the uterus, excessive traction to relieve dystocia or retained fetal membranes, uterine atony, hypocalcemia, and lack of exercise have all been incriminated as contributory causes. Prolapse of the uterus invariably occurs immediately after or within several hours of parturition, when the cervix is open and the uterus lacks tone. Prolapse of the postgravid uterine horn usually is complete in cows, and the mass of uterus usually hangs below the hocks. The invagination of the contralateral horn can be located by careful examination of the surface of the prolapsed organ. In sows, one horn may become everted while unborn piglets in the other prevent further prolapse. In small animals, complete prolapse of both uterine horns is usual. In cows, treatment involves removing the placenta (if still attached), thorough cleaning of the endometrial surface, and repairing any lacerations. Rubbing the surface of the uterus with glycerol helps reduce edema and provides lubrication. The uterus is then returned to its normal position. An epidural anesthetic should be administered first. If the cow is standing, the cleansed uterus should be elevated to the level of the vulva on a tray or hammock supported by assistants, and then replaced by applying steady pressure beginning at the cervical portion (or at the level of the invagination of the nonprolapsed uterine horn) and gradually working toward the apex. Once the uterus is replaced, the hand should be inserted to the tip of both uterine horns to be sure that there is no remaining invagination that could incite abdominal straining and another prolapse. Installation of warm, sterile saline solution is useful for ensuring complete replacement of the tip of the uterine horn without trauma. If recumbent, the cow should be positioned with the hindquarters elevated by placing her in sternal recumbency with the hindlegs extended backward. Resection of the uterus is indicated in long-standing cases in which tissue necrosis has occurred. Once the uterus is in its normal position, oxytocin (20 IU, IV, or 40 IU, IM) is administered to increase uterine tone. Administration IV of calcium-containing solutions is indicated in most cases, also as a means of increasing uterine tone. Caslick sutures or other forms of vulvar closure are not useful because the uterine prolapse begins at the apex of the uterine horn, and prevention of recurrence depends on complete and correct replacement of the uterus. The prognosis depends on the amount of injury and contamination of the uterus. In the cow, amputation of a severely traumatized or necrotic uterus may be the only means of saving the animal. Supportive treatment and antibiotic therapy are indicated. Vaginal And Cervical Prolapse: Introduction Eversion and prolapse of the vagina, with or without prolapse of the cervix, occurs most commonly in cattle and sheep. A form of vaginal prolapse, different in pathogenesis, also occurs in dogs (see vaginal hyperplasia, Vaginal Hyperplasia ). In cattle and sheep, the condition is usually seen in mature females in the last trimester of pregnancy. Predisposing factors include increased intra-abdominal pressure associated with increased size of the pregnant uterus, intra-abdominal fat, or rumen distention superimposed upon relaxation and softening of the pelvic girdle and associated soft-tissue structures in the pelvic canal and perineum mediated by increased circulating concentrations of estrogens and relaxin during late pregnancy. Intra-abdominal pressure is increased in the recumbent animal. Added to this, sheep tend to face uphill when lying down, so that gravity assists vaginal eversion and prolapse. The prolapse begins as an intussusception-like folding of the vaginal floor just cranial to the vestibulovaginal junction. Discomfort caused by this eversion, coupled with irritation and swelling of the exposed mucosa, results in straining and more extensive prolapse. Eventually the entire vagina may be prolapsed, with the cervix conspicuous at the most caudal part of the prolapsus. The bladder or loops of intestine may be contained within the prolapsed vagina. As the bladder moves into the prolapsed vagina, the urethra may be occluded. The bladder then fills and enlarges, which hinders replacement of the prolapsed vagina unless the bladder is first drained. The bladder may even rupture with potentially fatal consequences. Although most common in mature animals in late pregnancy, vaginal prolapse occurs in young, nonpregnant ewes and heifers, especially in fat animals. Predisposing factors include grazing estrogenic plants (especially Trifolium subterraneum ) or exogenous administration of estrogenic compounds (usually in the form of growth-promotant implants). Cervicovaginal prolapse is more common in stabled than in pastured animals, suggesting that lack of exercise may be a contributing factor. In pigs, vaginal prolapse is often associated with estrogenic activity of mycotoxins. The vagina is well lubricated (glycerin provides lubrication and reduces congestion and edema by osmotic action) and replaced and then held in position until it feels warm again. Retention is achieved by insertion of a Buhner suture (a deeply buried, circumferential suture placed around the vestibulum to provide support at the point at which the initial eversion of

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the vaginal wall occurs), which prevents the initiation of the condition. Buhner sutures should generally be removed before parturition to prevent extensive laceration. Dystocia Difficult birth may result from myometrial defects, metabolic abnormalities such as hypocalcemia, inadequate pelvic diameter, insufficient dilation of the birth canal, fetal hormone (corticosteroid) deficiency, fetal oversize, fetal death, or abnormal fetal presentation and posture. Dystocia should be considered in any of the following situations: 1) an animal has a history of previous dystocia or reproductive tract obstruction; 2) parturition does not occur within 24 hr after the drop in rectal temperature (to 21 days, or when proestrus plus estrus have lasted for >40 days. Estrous cycles due to follicular cysts in queens may be difficult to differentiate from normal, frequent cycles. An estrogensecreting ovarian tumor is the other diagnostic consideration. Ovariohysterectomy is curative. If the animal is to be bred, ovulation may be induced by using gonadotropin-releasing hormone (Gn-RH). Gn-RH is not an effective treatment for ovarian tumors. Mammary Hypertrophy Hyperplasia Complex in Cats (Feline mammary hypertrophy, Mammary fibroadenomatosis, Mammary fibroadenoma, Fibroglandular mammary hypertrophy) This benign, noninflammatory condition is characterized by rapid abnormal growth of one or more mammary glands. There are two basic types of hyperplasia of the feline mammary gland—lobular hyperplasia and fibroepithelial hyperplasia. Lobular hyperplasia is seen as palpable masses in one or more mammary glands in intact cats 1-14 yr old. Fibroepithelial hyperplasia occurs in young, cycling, or pregnant cats; in old, intact females and males; and in neutered males after treatment with progestins. Feline mammary hypertrophy is considered to be a hormone-dependent dysplastic change in the mammary gland. Hyperplasia occurs within 1-2 wk after estrus or 2-6 wk after progestin treatment. The tremendously enlarged glands may appear erythematous, and some of the skin may be necrotic. Edema of the skin and both hindlegs is common, and the condition can easily be confused with acute mastitis. Ovariectomy or mastectomy is curative, although spontaneous remissions occur. Ovariectomy is followed by regression of the glands and prevents recurrence. Merck Veterinary Manual - Summary

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Mastitis Mastitis can be septic or nonseptic and involve one or more mammary glands, usually during lactation. Septic mastitis can result from an ascending infection from the nipples or penetrating wounds, or via hematogenous spread. Staphylococci, streptococci, and E coli are the most common bacteria isolated from the milk. The source of infection usually is not found. Affected mammary glands are usually swollen, warm, and painful. Milk from affected glands may be hemorrhagic or purulent, may have an alkaline pH, and often is more viscous than normal milk. The bitch or queen may or may not show signs of illness such as fever, listlessness, inappetence, and neglect of the young. Diagnosis is made easily from the history and physical examination. Milk from each gland should be evaluated in any postpartum bitch or queen with signs of systemic illness. Broad-spectrum, bactericidal antibiotics should be chosen based on sensitivity tests and with the realization that they will be passed in the milk to the young. Antibiotics such as tetracycline, chloramphenicol, or aminoglycosides should be avoided during lactation unless the neonates are weaned. Hot-packing the affected glands encourages drainage and seems to relieve discomfort. Fluid therapy is indicated in animals with septic mastitis that are dehydrated or in shock. An abscessed mammary gland should be lanced, drained, flushed, and treated as an open wound. Nonseptic mastitis occurs most commonly at weaning. Pyometra Pyometra is a hormonally mediated diestrual disorder characterized by an abnormal uterine endometrium with secondary bacterial infection. In the normal bitch, the corpora lutea produce progesterone for 9-12 wk after ovulation in each estrous cycle. If pregnancy does not occur after a cat is induced to ovulate, the life span of the corpora lutea is ~45 days. Etiology: Factors associated with occurrence of pyometra include administration of long-lasting progestational compounds to delay or suppress estrus, administration of estrogens to mismated bitches, and postinsemination or postcopulation infections. Progesterone promotes endometrial growth and glandular secretion while decreasing myometrial activity. Cystic endometrial hyperplasia and accumulation of uterine secretions ultimately develop and provide an excellent environment for bacterial growth. Progesterone may also inhibit the WBC response to bacterial infection. Bacteria from the normal vaginal flora or subclinical urinary tract infections are the most likely source of uterine contamination. Escherichia coli is the most common bacterium isolated in cases of pyometra, although Staphylococcus , Streptococcus , Pseudomonas , Proteus spp , and other bacteria also have been recovered. Because queens require copulatory stimulation to ovulate, form corpora lutea, and produce progesterone, pyometra is less common in queens than in bitches. Estrogen, by itself, does not contribute to the development of cystic endometrial hyperplasia or pyometra. However, it does increase the stimulatory effects of progesterone on the uterus. Administration of exogenous estrogens to prevent pregnancy (ie, “mismate shots”) during diestrus greatly increases the risk of developing pyometra and should be discouraged. Clinical and Laboratory Findings: Clinical signs are seen during diestrus, usually 4-8 wk after estrus, or after administration of exogenous progestins. The signs are variable and include lethargy, anorexia, polyuria, polydipsia, and vomiting. When the cervix is closed, there is no discharge and the large uterus may cause abdominal distention. Signs can progress rapidly to shock and death. Physical examination reveals lethargy, dehydration, uterine enlargement, and if the cervix is patent, a sanguineous to mucopurulent vaginal discharge. Only 20% of affected animals have a fever. Shock may be present. The leukogram of animals with pyometra is variable and may be normal; however, leukocytosis characterized by a neutrophilia with a left shift is usual. Leukopenia may be found in animals with sepsis. A mild, normocytic, normochromic, nonregenerative anemia (PCV of 28-35%) may also develop. Hyperproteinemia due to hyperglobulinemia may be found. Results of urinalysis are variable. With E coli uterine infection, isosthenuria due to endotoxin-induced impairment of renal tubular function or to insensitivity to antidiuretic hormone (or both) may develop. A glomerulonephropathy caused by immune-complex deposition may result in proteinuria. These renal lesions are potentially reversible once the pyometra is resolved. Diagnosis: Pyometra should be suspected in any ill, diestrual bitch or queen, especially if polydipsia, polyuria, or vomiting is present. The diagnosis can be established from the history, physical examination, and abdominal radiography and ultrasonography. Vaginal cytology is often helpful in determining the nature of the vulvar discharge. The complete blood count, biochemical profile, and urinalysis help exclude other causes of polydipsia and polyuria and vomiting; they also evaluate renal function, acid-base status, and septicemia. Treatment and Prognosis:

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Ovariohysterectomy is the treatment of choice, but medical management could be considered if it is desired to salvage the reproductive potential of the bitch or queen. Fluids (IV) and broad-spectrum, bactericidal antibiotics should be administered. Medical therapy with prostaglandin (PG) F2α can be used for animals to be bred in the future, although prostaglandins are not approved in the USA for use in cats or dogs. Prostaglandins cause luteolysis, contraction of the myometrium, relaxation of the cervix, and expulsion of the uterine exudate. Probably, they should not be used in animals >8 yr old or those not intended for breeding. The delay before clinical improvement and the many side effects of PGF2α preclude its use in a severely ill animal. PGF2α also should be used with caution in the bitch or queen with a closed-cervix pyometra because the risk of uterine rupture is increased. Pregnancy must be ruled out because prostaglandins can induce abortion. Only naturally occurring PGF2α (0.25 mg/kg body wt, SC, s.i.d. for 5 days) should be used in the bitch and queen. Other effects of PGF2α include restlessness, anxiety, panting, hypersalivation, pacing, abdominal pain, tachycardia, vomiting, urination, and defecation. In cats, vocalization and intense grooming behavior also may be seen. These reactions disappear within 2 hr of the injection. The LD50 of PGF2α in dogs is 5.13 mg/kg body wt. Severe ataxia, respiratory distress, and muscle tremors may be seen in queens given 5 mg/kg. If severe side effects occur, IV fluids at rates appropriate for treatment of shock are indicated. Uterine evacuation after an injection is variable. Daily vaginal douches with tepid 1% tamed iodine solution are beneficial in promoting vaginal drainage, cervical dilation, and uterine evacuation. Usually, the prognosis for an animal undergoing ovariohysterectomy is good. After medical therapy, the prognosis for initial resolution of the pyometra is good if the cervix is open, but guarded to poor if closed. Of those animals that respond, as many as 90% of the bitches and 70% of the queens with open-cervix pyometra may be fertile. Only 50% of bitches with closed-cervix pyometra are reported to return to fertility. Recurrence is likely—of bitches treated medically for pyometra, 70% had recurrence within 2 yr. Therefore, the animal should be bred on the next and each subsequent cycle until the desired number of puppies or kittens has been obtained, and then spayed. Vaginal Hyperplasia In vaginal hyperplasia, a proliferation of the vaginal mucosa, usually originating from the floor of the vagina anterior to the urethral orifice, occurs during proestrus and estrus, as a result of estrogenic stimulation. The most common sign is a mass protruding from the vulva. Initially, the mass is smooth and glistening, but with prolonged exposure, the surface becomes dry and fissures develop, so it has a tongue-like appearance. A slight vaginal discharge may be present. Although the hyperplastic tissue originates near the urethral orifice, dysuria is uncommon. Vaginal hyperplasia interferes with copulation. Reluctance to breed or failure of intromission may be the only clinical sign if the hyperplastic tissue is contained within the vaginal vault. Vaginal hyperplasia resolves spontaneously as soon as estrogen declines. The diagnosis is made by the history (stage of the estrous cycle) and examination of the vagina. Estrogenic stimulation could be confirmed by vaginal cytology if the history is questionable. The two differential diagnoses are vaginal prolapse (excluded by the history and physical findings) and neoplasia (excluded by biopsy). If the hyperplastic tissue is not causing problems, therapy is not indicated. However, if it protrudes from the vulva, it should be kept clean and moist and an antibiotic ointment applied. An Elizabethan collar may be necessary to prevent self-trauma. These animals may be bred by artificial insemination. The hyperplasia regresses as soon as the follicular phase of the estrous cycle has passed. Rarely, the hyperplasia recurs at parturition, presumably associated with a burst of estrogen. Vaginitis Inflammation of the vagina may occur in prepubertal or mature (intact or spayed) bitches. It is rare in queens. Vaginitis usually is due to bacterial infection, which may be secondary to conformational abnormalities such as vestibulovaginal strictures. Viral infection (eg, herpes), vaginal foreign bodies, neoplasia, hyperplasia of the vagina, androgenic steroids (eg, mibolerone), or intersex conditions also may cause vaginitis. The most common clinical sign is a vulvar discharge. Licking of the vulva, attraction of males, and frequent micturition also may be seen. Signs of systemic illness are not present, and the hemogram and biochemical profile are normal. The absence of these abnormalities helps differentiate vaginitis from open-cervix pyometra, the most important differential diagnosis. Prepubertal animals often do not require treatment because the vaginitis nearly always resolves with the first estrus. Therefore, it may be wise to delay elective ovariohysterectomy in affected animals until after their first estrous cycle. Prostatic Diseases: Introduction Diseases of the prostate gland are relatively common in dogs but less common in other species. Benign prostatic hyperplasia, bacterial prostatitis, prostatic abscesses, prostatic and paraprostatic cysts, and prostatic adenocarcinoma are the most common prostatic disorders in dogs. These disorders all cause enlargement or inflammation of the prostate gland and, therefore, have similar clinical signs. Typical signs include tenesmus during defecation, intermittent hematuria, recurrent urinary tract infections, and caudal abdominal discomfort. Additional nonspecific signs, such as fever, malaise, anorexia, severe stiffness, and caudal abdominal pain, are often present with bacterial infections and neoplasia. Prostatic Merck Veterinary Manual - Summary

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adenocarcinoma with bony involvement of the pelvis and lumbar vertebrae may cause hindlimb gait abnormalities. Prostatic enlargement may mechanically interfere with other abdominal organs. Less commonly, prostatic diseases may cause infertility, urinary incontinence, or complete urethral obstruction. Physical examination of the prostate gland should include abdominal and rectal palpation. An enlarged prostate usually is located further cranial than usual and can be found in the caudal abdomen, rather than within the pelvic canal. Size, shape, symmetry, consistency, mobility, and the presence or absence of pain are assessed by palpation. The normal dorsal sulcus (depression) helps in assessment of shape and symmetry. The historical and physical findings are usually sufficient to localize a disease process to the prostate gland but not to differentiate between the various conditions. Abdominal radiographs may further define the size, shape, and position of the prostate gland. The sublumbar lymph nodes, lumbar vertebrae, and bony pelvis should be evaluated radiographically for evidence of periosteal new bone and bony metastases. A positive-contrast retrograde urethrogram can be done when an abnormal prostate or paraprostatic cyst is difficult to differentiate from the bladder. Ultrasonography may provide additional information concerning echogenicity of the prostatic parenchyma and may identify focal prostatic lesions that cannot be palpated. Mass lesions within the prostatic urethra and discontinuity of the prostatic urethral wall are both highly suggestive of prostatic neoplasia. Material for cytologic and microbiologic examination can be obtained by a combination of prostatic massage and urethral catheterization. Material is aspirated from the prostatic urethral lumen using a rubber or plastic urinary catheter. It is usually helpful to have a finger in the dog's rectum during the procedure, so that the position of the tip of the catheter is known. Alternatively, the prostatic fraction of the ejaculate can be collected. Transcutaneous fine-needle aspiration of prostatic parenchyma and biopsy of the prostate gland are also excellent methods. Prostatic massage is easily performed; however, samples are routinely contaminated with urine from the bladder. Because prostatic fluid normally refluxes into the bladder, urinary tract infection is usually present with bacterial prostatitis. Microbiologic examination of the prostatic (third) fraction of the ejaculate is more accurate for assessment of prostatic infection than is examination of prostatic massage specimens when urinary tract infection is present. Biopsy is the most definitive, but also the most invasive, diagnostic procedure for differentiating prostatic diseases. Benign Prostatic Hyperplasia Benign prostatic hyperplasia is the most common prostatic disorder and is found in most intact male dogs >6 yr old. It is a result of androgenic stimulation or altered androgen/estrogen ratio, but why some males are affected and others are not is unknown. In some dogs, hyperplasia may begin as early as 2½ yr of age and, after 4 yr of age, cystic hyperplasia tends to develop. There may be no clinical signs, or tenesmus, persistent or intermittent hematuria, and bleeding may occur. The diagnosis is suggested by physical and historical findings and by a nonpainful and symmetrically enlarged prostate. Radiology can confirm prostatomegaly. Ultrasonography should show diffuse, relatively symmetrical involvement with multiple, diffuse, cystic structures. Cytologic examination of massage or ejaculate specimens reveals hemorrhage with mild inflammation without evidence of sepsis or neoplasia. Definitive diagnosis is only possible by biopsy. Castration is the treatment of choice; prostatic involution is usually evident within a few weeks and is often complete in several months. For males intended for use in breeding, other therapy (eg, antiandrogens) may be feasible, but none is currently recognized to be as safe or effective as castration. The drugs that either inhibit androgen synthesis or counteract the effects of androgens have the potential of inhibiting spermatogenesis; therefore, their long-term use may not have a more desirable outcome than castration. Estrogens have been used to reduce prostatic hyperplasia but cannot be recommended because of potential side effects. Whenever estrogenic stimulation is present (eg, exogenous administration or endogenous production by Sertoli cell tumor), squamous metaplasia of the prostate can develop. Squamous metaplasia can cause prostatic enlargement and worsen the clinical signs. It may also enhance the risk of cystic changes and infection within the prostate. In addition, estrogens can cause negative feedback to the hypothalamus and pituitary (thereby diminishing spermatogenesis) and are potentially toxic to the bone marrow, with resultant anemia, thrombocytopenia, and leukopenia. Prostatitis Inflammation of the prostate gland usually is suppurative and may result in abscesses. It may be associated with prostatic hyperplasia (see Benign Prostatic Hyperplasia). Various organisms, including Escherichia coli , Staphylococcus , Streptococcus , and Mycoplasma spp , have been incriminated. Infection may be hematogenous or ascending from the urethra. Because prostatic fluid normally refluxes into the bladder, urinary tract infection often accompanies prostatic infection. The signs resemble those of prostatic hyperplasia. In addition, malaise, pain, and fever are common. Dehydration, septicemia, and shock may occur in severe cases of acute bacterial prostatitis or prostatic abscess. The historical, physical, and radiographic findings are suggestive of acute bacterial prostatitis and abscesses. Neutrophilia with a left shift, monocytosis, and/or toxic WBC may be seen. Ultrasonography shows hypoechoic areas consistent with pockets of fluid. Ideally, prostatic material is obtained by prostatic massage, ejaculation, or fine-needle Merck Veterinary Manual - Summary

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aspiration for cytologic examination and for culture and sensitivity testing. Massage of an acutely infected prostate may liberate organisms into the blood and cause septicemia. For this reason, other methods are preferred. However, dogs with acute bacterial prostatitis or abscesses may be reluctant to ejaculate, and fine-needle aspiration may release organisms into the peritoneal cavity. Urinalysis shows hematuria, pyuria, and bacteriuria. The urine should be submitted for culture and sensitivity testing. Often, the urine and prostatic material yield the same organisms. Chronic bacterial prostatitis may cause no clinical signs except recurrent urinary tract infection. Physical abnormalities may be limited to the urinary tract. Rarely, prostatic size and shape may be normal. Dogs with chronic bacterial prostatitis are usually willing to ejaculate. Prostatic fluid and urine should be submitted for cytologic and microbiologic examination. Prostatic massage or fine-needle aspiration could also be used to obtain specimens. Fluid therapy is indicated when acute prostatitis is associated with dehydration or shock. Antibiotics should be selected on the basis of sensitivity testing and given for 1-4 wk. Large prostatic abscesses are best treated by surgical drainage. Chronic bacterial prostatitis may be difficult to resolve. Prostatic and Paraprostatic Cysts Large cysts are occasionally found within or associated with the prostate gland. The signs are similar to those seen with other types of prostatic enlargement and usually become apparent only when the cyst reaches a size sufficient to cause pressure on adjacent organs. Large cysts may result in abdominal distention and must be differentiated from the bladder and from prostatic abscesses. Medical treatment is ineffective, and estrogen therapy is contraindicated. Total excision of the cyst is the only satisfactory treatment. Surgical excision is preferable to marsupialization because chronic management of the fistula is often problematic. Neoplasms Adenocarcinoma is the most common neoplasm of the prostate. Transitional cell carcinoma arising from the bladder occasionally invades the prostate. The clinical signs of prostatic neoplasia are similar to those of other prostatic diseases. Pain and fever may be present. If the neoplasm infiltrates the urethra, dysuria or urethral obstruction is likely. Prostatic adenocarcinoma metastasizes to the regional lymph nodes, lumbar vertebrae, and bony pelvis. Diagnosis is made by biopsy. There is no effective curative treatment. Consultation with a veterinary oncologist is recommended.

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Respiratory System The three main groups of species that have anatomically similar respiratory tracts are 1) cattle, sheep, and pig; 2) dog, cat, monkey, rat, rabbit, and guinea pig; and 3) horse and man. Marked physiologic variations also exist between different species. For example, cattle are prone to retrograde drainage from the pharynx, are predisposed to pulmonary hypertension and reduced ventilation in a cold environment, have relatively small lungs with low tidal volume and functional residual capacity, and are more sensitive to changes in environmental temperatures than are most other species. These anatomic and physiologic differences largely determine why some pathogens affect only some species (eg, Pasteurella haemolytica affects cattle but not pigs) and why pneumonia is very important in some species (cattle, pigs) but less so in others (dogs, cats). Clinical Signs of Respiratory Malfunction: Nasal discharge may be serous, catarrhal, purulent, or hemorrhagic, depending on the degree of mucosal damage. It indicates increased production of normal secretions, sometimes supplemented by neutrophils (purulent) or blood (hemorrhage). It probably also indicates decreased “grooming” of the nostrils with the tongue when animals are ill. Epistaxis (hemorrhage from the nose) is often caused by vascular rupture, such as in mycotic infection of the guttural pouch or exercise-induced pulmonary hemorrhage in horses, or by intranasal fungal infection or neoplasia, systemic coagulopathy, vasculitis, thrombocytopenia (immune-mediated or result of rickettsial infection), hyperviscosity syndrome, or nasal trauma. Hemoptysis (the coughing up of blood) occurs after rupture of pulmonary aneurysms in the lungs of cattle with chronic lung abscesses. Bleeding may also result from polyps, neoplasms, granulomas, trauma, thrombocytopenia, and bracken fern or sweet clover toxicity. Hyperpnea (an increase in rate and depth of pulmonary ventilation) becomes dyspnea when the breathing appears labored and to be causing distress. Labored inhalation seen with obstructive diseases above the thoracic inlet (eg, tumors or exudates) or with pleural effusions is termed inspiratory dyspnea; labored expiration seen with obstructive diseases below the thoracic inlet (eg, diffuse bronchitis or emphysema) is termed expiratory dyspnea. Other responses include coughing, clear exudates, and shallow breathing with grunting, often associated with the pain of pleuritis. Fixed airway obstructions (eg, tracheal neoplasia or stenosis) or a combination of upper and lower obstructive airway diseases will result in both inspiratory and expiratory dyspnea. Causes of Respiratory Malfunction: The most common cause of upper respiratory tract malfunction is rhinitis (which results in exudation of neutrophils, macrophages, and fluids), or erosion and ulceration (or both) of the nasal mucosa. It may be caused by viral, bacterial, fungal, or parasitic agents, as well as by hypersensitivity reactions, such as localized allergies and anaphylaxis (see the immune system, Immunopathologic Mechanisms: Introduction et seq). Atrophy of the turbinates (eg, in atrophic rhinitis of pigs) removes a major filtration function and exposes the lungs to much heavier loads of dust and microorganisms. The nasal cavity may be obstructed by tumors, granulomas, abscesses, or foreign bodies. Sinusitis can be a complication of upper respiratory infections or dehorning. Laryngitis, tracheitis, and bronchitis result in coughing, inspiratory and expiratory dyspnea, and prolonged inspiration. Coughing may be dry if the irritation is caused by mucosal erosion, or productive if due to copious exudate in the major airways. Severe pulmonary edema and emphysema cause extreme respiratory insufficiency. The most common respiratory disease is pneumonia, which is defined as inflammation of the lungs. There are many systems for classifying the various types of pneumonia. One useful method is to classify according to the distribution of lesions in the lungs as follows: Focal pneumonia has one or more discrete foci in a random pattern, eg, abscessation due to emboli from other sites, tuberculosis, or actinomycosis. Lobular pneumonia accentuates the anatomic pattern of lobules, as in bronchopneumonia caused by Pasteurella multocida . Lobar pneumonia covers large areas of lobes and is often severe, such as in fibrinous pneumonic pasteurellosis of cattle. Diffuse or interstitial pneumonia often involves the entire lung, as in maedi of sheep or in hypersensitivity reactions. The appearance or etiology of a particular pneumonia can be described further, eg, gangrenous, parasitic (verminous), aspiration, etc. The initial problem in many pneumonias is thought to be a sudden alteration in the normal nasal bacterial flora, which results in a sudden dramatic increase in one or more species of bacteria. These bacteria are breathed into the lung in large numbers and may overwhelm the normal defense mechanisms, localize, multiply, and initiate inflammation. In addition, stress is often a precursor of viral respiratory infections, particularly in groups of animals that have recently been congregated and stressed by travel, handling, and mixing. Some respiratory viral infections can cause temporary dysfunction of phagocytic mechanisms of the alveolar macrophages. This usually occurs several days after viral exposure. Inhaled bacteria proliferate and pneumonia ensues, often with an overwhelming infection and massive exudation into the alveoli. Bronchiectasis is a chronic lesion of the bronchi and parenchyma characterized by irreversible cylindrical or saccular dilatation, secondary infection, and atelectasis. Ulceration of bronchioles caused by viral agents may lead to organized plugs of connective tissue in small bronchioles, a lesion called “bronchiolitis obliterans,” which may cause permanent obstruction, atelectasis, and severe respiratory insufficiency. Constriction of bronchioles in chronic allergic bronchitis and Merck Veterinary Manual - Summary

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bronchiolitis results in similar clinical signs. Some chronic pneumonias (eg, maedi in sheep) are characterized by firm diffuse lesions due to hyperplasia of lymphoid follicles, hyperplasia of smooth muscle around bronchioles, diffuse fibrosis, and diffuse lymphocytic infiltration. Aspiration pneumonia often leads to gangrene with severe toxemia accompanying the acute inflammatory reaction. Most infectious pneumonias occur in the anteroventral portions of the lungs. However, infectious agents, as well as neoplasms, can invade the lungs via the blood, which may extensively impair pulmonary function, as can pulmonary edema from chronic heart failure. Pleuritis, empyema, hydrothorax, chylothorax, atelectasis, diaphragmatic hernia, or pneumothorax can also seriously impair respiratory function. Pulmonary thrombosis leads to acute, often fulminant, respiratory failure as a result of a lack of pulmonary arterial blood flow to ventilated regions of the lung. Pulmonary edema , the abnormal accumulation of fluid in the interstitial tissue, airways, or alveoli of the lungs, may occur in conjunction with circulatory disorders, particularly left ventricular failure or increased capillary permeability, occasionally in anaphylactic and allergic reactions, and in some infectious diseases. Head trauma can cause pulmonary edema in dogs. Pleuritis (pleurisy) may be caused by any pathogen that gains entrance to the pleural cavity, but it is often an extension of pneumonia. Rapid shallow breathing, fever, and thoracic pain are suggestive of pleuritis. Auscultation of the chest may reveal friction sounds. Empyema (purulent exudate in the pleural cavity) is caused by pyogenic bacteria or fungi reaching the thoracic cavity via the blood or by extension of a pneumonia, traumatic reticulitis, or penetrating wounds of the chest. Cough, fever, pain, and dyspnea may be present. Hemothorax (the accumulation of blood in the pleural cavity) is usually caused by trauma to the thorax, systemic coagulopathy, or thoracic neoplasia. Hydrothorax (the accumulation of transudate in the pleural cavity) is usually due to interference with blood flow or lymph drainage. Chylothorax (the accumulation of chyle in the pleural cavity) is relatively rare and is seen most often in cats. It may be caused by rupture of the thoracic duct but often is idiopathic. The signs of all three conditions include respiratory embarrassment and weakness. Pneumothorax (air in the pleural cavity) may be of traumatic or spontaneous origin. Air can enter the pleural cavity through penetrating wounds of the thoracic wall or by extension from pulmonary emphysema or ruptured bullae. The lung collapses if a large volume of air enters the pleural cavity. Bilateral pneumothorax may develop if the mediastinum is weak or incomplete. Dyspnea is evident. Control of Respiratory Disease: Most of the lymphocytes in the respiratory lining produce only IgA, whereas the cells in the lymph nodes of the respiratory tract produce IgM and IgG. Depending on the agent involved, various cell- and antibody-mediated immune responses occur in the respiratory tract and include opsonization, agglutination, immobilization, neutralization of toxin and virus, blockage of adherence to cells, lysis, and chemotaxis. Large droplets of antigen may immunize the upper tract with IgA, but small replicating particles may be necessary to immunize the lower tract. Principles of Therapy Respiratory disease is often characterized by abnormal production of secretions and exudates and by a reduced ability to remove them. The primary goal is to reduce the volume and viscosity of the secretions and to facilitate their removal. This can be accomplished by controlling infection, modifying the secretions, and when possible, improving postural drainage and mechanically removing the material. Therapeutic methods include altering the inspired air and administering expectorants, antitussives, bronchodilators, antimicrobials, diuretics, and other drugs. Hydration should be maintained. Inhalation of humidified air may facilitate removal of airway secretions. Expectorants are sometimes used with the intention of liquefying these secretions. However, they should be used in conjunction with ancillary respiratory therapy such as improved postural drainage, mild exercise, and thoracic percussion, which (in addition to coughing) encourages expectoration and removal of secretions. The value of expectorants at traditional dosages is questioned. Mechanical removal of tenacious and viscid secretions by aspiration may be necessary in severe airway obstruction. Antitussive agents are indicated to relieve the discomfort associated with unproductive coughing but are contraindicated when secretion of airway mucus is excessive. Products that contain atropine also are contraindicated, at least in theory, because atropine increases the viscosity of airway secretions. Increased airway resistance caused by bronchial smooth muscle contraction can be alleviated with bronchodilators, which may be indicated in animals with asthma-like conditions and chronic respiratory disease. Methylxanthines, such as theophylline and aminophylline, are effective bronchodilators in species other than cattle. Isoproterenol, clenbuterol, and epinephrine are also generally effective, and sodium cromoglycate is used in horses for treating small airway disease (eg, heaves). The use of corticosteroids is justified in allergic conditions. Antihistamines can be used to alleviate the bronchoconstriction caused by histamine release. Bronchospasm also can be reduced significantly by removing irritating factors, using mild sedatives, or reducing periods of excitement. Merck Veterinary Manual - Summary

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In bacterial infection, antimicrobial therapy should be instituted. The basic goal is to select either the most effective agent against a specific organism or the least toxic agent of several alternatives. The following agents have proved effective in the listed species: cattle—oxytetracycline, erythromycin, penicillins, and sulfonamides; sheep and goats— oxytetracycline, penicillins, and sulfonamides; pigs—lincomycin, spectinomycin, penicillins, and sulfonamides; dogs and cats—cephalosporins, chloramphenicol, erythromycin, lincomycin, clindamycin, penicillins, sulfonamides, and tetracyclines; horses—penicillins, sulfonamides, and tetracyclines, the latter with caution due to an occasional side effect of severe diarrhea. Aminoglycosides are useful but can be nephrotoxic. Trimethoprim, usually in combination with a sulfonamide, is useful for respiratory therapy in most species but is not licensed for food-producing animals in the USA. New drugs such as enrofloxacin (approved for small but not large animals in the USA) and ceftiofur may prove to be efficacious. Diuretics are indicated in pulmonary edema. The osmotic diuretics have a minimal action on diuresis. Carbonic anhydrase inhibitors (eg, acetazolamide) have a moderate action on duiresis, and loop diuretics (eg, furosemide) have a profound effect. Aspiration Pneumonia: Introduction (Foreign-body pneumonia, Inhalation pneumonia, Gangrenous pneumonia) Etiology: Faulty administration of medicines is the most common cause. Liquids administered by drench or dose syringe should not be given faster than the animal can swallow. Drenching is particularly dangerous when the animal's tongue is drawn out, when the head is held high, or when the animal is coughing or bellowing. Animals (especially cats) are particularly susceptible to pneumonia caused by aspiration of tasteless products such as mineral oil. Inhalation of food sometimes occurs in calves and pigs. Disturbances of deglutition, as in anesthetized or comatose animals (eg, mature cattle under general anesthesia or cows in lateral recumbency), vagal paralysis, acute pharyngitis, abscesses or tumors of the pharyngeal region, esophageal diverticula, cleft palate, megaesophagus or encephalitis, are frequent predisposing causes. Atropine sulfate helps to control salivation stimulated by anesthetics (eg, thiobarbiturates). Use of an endotracheal tube with an inflatable cuff prevents fluid aspiration during surgery. Clinical Findings: A clinical history suggesting recent foreign-body aspiration is of great diagnostic value. Horses may develop fevers of 104-105°F (40-40.5°C), which can drop back into the normal range in a few days. Pyrexia is also seen in cats, dogs, and less commonly in cattle. The pulse is accelerated, and respiration is rapid and labored. A sweetish, fetid breath characteristic of gangrene may be detected, the intensity of which increases with disease progression. This is often associated with a purulent nasal discharge that sometimes is tinged reddish brown or green. In cows that aspirate ruminal contents, toxemia is usually fatal within 1-2 days. Recovered animals often develop pulmonary abscesses. Lesions: The pneumonia is usually in the anteroventral parts of the lungs; it may be unilateral or bilateral and centers on airways. In the early stages, the lungs are markedly congested with areas of interlobular edema. Bronchi are hyperemic and full of froth. Suppuration and necrosis follow, the foci becoming soft or liquefied, reddish brown, and foul smelling. Treatment: The animal should be kept quiet. A productive cough should not be suppressed. Broad-spectrum antibiotics should be used in animals known to have inhaled a foreign substance, whether it be a liquid or an irritant vapor, without waiting for signs of pneumonia to appear. Care and supportive treatment are the same as for infectious pneumonias. In small animals, oxygen therapy may be beneficial. Despite all treatments, prognosis is poor, and efforts must be directed at prevention. Chlamydial Pneumonia: Introduction Chlamydiae have been identified in various parts of the world as a cause of enzootic pneumonia in calves, mice, sheep, piglets, foals, and goats. Etiology and Epidemiology: The causative agent is Chlamydia psittaci . Some respiratory isolates from calves have properties of immunotypes 1 and 6 and are similar to strains recovered from intestinal infections ( Intestinal Chlamydial Infections: Introduction) and abortions of cattle and sheep ( Abortion In Large Animals: Introduction). Immunotype 6 has been recovered from pneumonic lungs of calves and pigs. Thus, the GI tract must be considered as an important site in the pathogenesis of chlamydial infections and as a natural reservoir and source of the organisms. Clinical Findings and Lesions: Calves, lambs, and goats with chlamydial pneumonia are usually febrile, lethargic, and dyspneic, and have a serous and later mucopurulent nasal discharge and a dry hacking cough. Calves of weanling age are affected most frequently, but older cattle may also show signs.

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The acute pulmonary lesion is a bronchointerstitial pneumonia. The anteroventral parts of the lungs are affected but, in severe cases, entire lobes can be involved. The dry cough is attributed to tracheitis. Microscopic changes in the lungs include suppurative bronchitis and alveolitis progressing to type II pneumocyte hyperplasia and interstitial thickening. Diagnosis: Diagnosis requires isolation of chlamydiae from affected tissues in a tissue culture or chick embryo. Predominantly, IgG2 antibodies are induced by chlamydial infections in cattle. Prevention and Treatment: Vaccines are not available. Several antimicrobials (eg, penicillin, erythromycin, tylosin, and tetracyclines) can interfere with chlamydial multiplication, but tetracyclines are generally the drug of choice. Treatment must start as early as possible. Diaphragmatic Hernia: Introduction A break in the continuity of the diaphragm allows protrusion of abdominal viscera into the thorax. Etiology: In small animals, automobile-related trauma is a common cause of diaphragmatic hernia, although congenital defects of the diaphragm may also result in herniation (eg, peritoneopericardial hernia). In horses, diaphragmatic hernia may occur less commonly after trauma, dystocia, or breeding. In cattle, there is rarely a history of trauma, and hernias are reportedly associated with traumatic reticulitis, with a greater prevalence in buffalo. Clinical Findings: If the stomach is herniated, it may bloat and the animal may deteriorate rapidly. In chronic cases, systemic signs such as weight loss may be more prominent than respiratory signs. Diagnosis: The definitive diagnosis is most frequently made from radiographs. Loss of diaphragmatic contour, abdominal viscera in the thorax, and the displacement of viscera from the abdomen may be apparent. Treatment: Surgical repair of the hernia is the only treatment. Hypostatic Pneumonia: Introduction In hypostatic pneumonia, blood is unable to pass readily through the vascular structures of the lungs, which may lead to a shift in fluid from the vascular to the pulmonary spaces. The condition is due to passive or dependent congestion of the lungs and is seen most commonly in older or debilitated animals. It is usually secondary to some other disease process (eg, congestive heart failure). Recumbent animals, such as those recovering from anesthesia, may develop hypostatic pneumonia if not repositioned regularly. Coughing is not always a clinical prominent sign, but as the condition progresses, dyspnea and cyanosis become apparent. The animal's position must be changed hourly. Use of narcotics and sedatives should be minimal to encourage movement and to avoid suppression of the cough reflex. Laryngeal Disorders: Introduction See also laryngeal hemiplegia, Laryngeal Hemiplegia . Laryngitis, an inflammation of the mucosa or cartilages of the larynx, may result from upper respiratory tract infection or by direct irritation from inhalation of dust, smoke, or irritating gas; foreign bodies; or the trauma of intubation, excess vocalization, or in livestock, by injury from roping or restraint devices. Laryngitis may accompany infectious tracheobronchitis and distemper in dogs; infectious rhinotracheitis and calicivirus infection in cats; infectious rhinotracheitis and calf diphtheria in cattle; strangles, herpesvirus 1 infection, viral arteritis, and infectious bronchitis in horses; Fusobacterium necrophorum or Corynebacterium pyogenes infections in sheep; and influenza in pigs. Edema of the mucosa and submucosa is often an integral part of laryngitis and, if severe, the rima glottidis may be obstructed. Edema may also result from allergy, inhalation of irritants, or surgery in the area. Intubation for anesthesia, especially when attempted with inadequate induction or poor technique, is likely to provoke laryngeal edema. Brachycephalic and obese dogs, and dogs with laryngeal paralysis (see Laryngeal Paralysis) develop laryngeal edema and laryngitis through severe panting or respiratory effort during excitement or hyperthermia. In cattle, laryngeal edema has been seen in blackleg, urticaria, serum sickness, and anaphylaxis. In pigs, it may occur as a part of edema disease. In horses, cattle, and sheep, laryngeal edema may lead to arytenoid chondropathy. Laryngeal chondropathy is a suppurative condition of the cartilage matrix that principally affects the arytenoid cartilages; it is believed to result from microbial infection. Initially, there is often acute laryngeal inflammation. Later, there is progressive enlargement of the cartilages that commonly results in a fixed upper airway obstruction with stertorous breathing and reduced exercise tolerance. Laryngeal chondropathy occurs in horses, sheep, and cattle, most often young males. There is a distinct breed predisposition in Thoroughbred horses in race training, Texel and Southdown sheep, and Belgian Blue cattle. Clinical Findings: Merck Veterinary Manual - Summary

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A cough is the principal sign of laryngitis when edema is slight and the deeper tissues of the larynx are not involved. It is harsh, dry, and short at first, but becomes soft and moist later and may be very painful. Vocal changes may be evident, especially in small animals. Halitosis and difficult, noisy breathing may be evident, and the animal may stand with its head lowered and mouth open. Swallowing is difficult and painful. Edema of the larynx may develop within hours. It is characterized by increased inspiratory effort and stridor arising from the larynx. Respiratory rate may slow as the effort of breathing becomes exaggerated. Visible mucous membranes are cyanotic, the pulse rate is increased, and body temperature rises. Horses may sweat profusely. Untreated animals with marked obstruction eventually collapse and often have signs of pulmonary edema. Diagnosis: A tentative diagnosis is based on the clinical signs, auscultation of the laryngeal region, and exacerbation of stridor by palpation of the larynx. Definitive diagnosis requires laryngoscopy. In conscious horses and cattle, this can be achieved with a flexible endoscope passed per nasum; in dogs and cats, usually anesthesia or analgesia is required. Bilateral laryngeal paralysis, laryngeal abscess, pharyngeal trauma and cellulitis, and retropharyngeal abscesses or masses can cause similar signs. Treatment: In laryngeal obstruction, a tracheotomy tube should be placed immediately; if a tracheotomy is not immediately possible, it may be possible to establish airway patency by passage of a pliable tube through the glottis. Corticosteroids should be administered to reduce the obstructive effect of the inflammatory swellings. Concurrent administration of nonsteroidal anti-inflammatory drugs and systemic antibiotics is also necessary. Administration of diuretic drugs, eg, furosemide, may be indicated for resolution of laryngeal edema and, if present, pulmonary edema. The cough may be suppressed with antitussive preparations, and bacterial infections controlled with antibiotics or sulfonamides. Control of pain with judicious use of an analgesic, especially in cats, allows the animal to eat, and thus speeds recovery. Subtotal arytenoidectomy is an effective remedy for laryngeal chondropathy of horses, sheep, and cattle, although a return to full athletic capacity in competitive horses is uncertain. Laryngeal Paralysis This disease of the upper airway is common in dogs and rare in cats. Signs include a dry cough, voice changes, noisy breathing that progresses to marked difficulty in breathing with stress and exertion, stridor, and collapse. Regurgitation and vomiting may occur. Progression of clinical signs is slow, usually taking months to years before respiratory distress is evident. It is a common acquired problem in middle-aged to older, large and giant breeds of dogs, eg, Labrador Retrievers, Irish Setters, and Great Danes. Diagnosis is based on clinical signs; laryngoscopy under light anesthesia is needed for confirmation. Laryngeal movements are absent or paradoxical with respiration. Electromyography shows positive sharp waves, denervation potentials, and sometimes myotonia. Radiographs are not diagnostic. Denervation atrophy is seen on histologic sections of laryngeal muscles. Differential diagnoses include myositis, recurrent laryngeal or vagal nerve tumor, inflammation, myasthenia gravis, severe hypothyroidism, trauma, and more widespread generalized neurologic degeneration. Therapy is directed at relieving signs of airway obstruction. Severe obstruction may require tracheotomy. Definitive therapy is surgical and is directed at enlarging the glottic opening. Lungworm Infection: Introduction (Verminous bronchitis, Verminous pneumonia) An infection of the lower respiratory tract, usually resulting in bronchitis or pneumonia, can be caused by any of several parasitic nematodes, including Dictyocaulus viviparus in cattle and deer; D arnfieldi in donkeys and horses; D filaria , Protostrongylus rufescens , and Muellerius capillaris in sheep and goats; Metastrongylus apri in pigs; Filaroides (Oslerus) osleri in dogs; and Aelurostrongylus abstrusus and Capillaria aerophila in cats. The first three lungworms listed above belong to the superfamily Trichostrongyloidea and have direct life cycles; the others belong to the Metastrongyloidea and, except for F osleri and C aerophila , have indirect life cycles. Some nematodes that inhabit the right ventricle and pulmonary circulation, eg, Angiostrongylus vasorum and Dirofilaria immitis , both found in dogs in certain areas of the world, may be associated with pulmonary disease. Clinical signs relating to a cardiac or a pulmonary syndrome or to a combination of both may occur. Diseases caused by the three Dictyocaulus spp are of most economic importance. Epidemiology: Dictyocaulus spp —Adult females in the bronchi lay larvated eggs that hatch either in the bronchi ( D viviparus ), or in host feces ( D arnfieldi ) after being coughed up and swallowed. The larvae can become infective in feces on pasture after a minimum of 1 wk in warm, moist conditions, but typically in summer in temperate northern climates will require 2-3 wk. A proportion of infective larvae will survive on pasture throughout the winter until the following year but, in very cold conditions, most will become nonviable. The principal source of new infections each year is from infected carrier animals, Merck Veterinary Manual - Summary

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with overwintered larvae providing a secondary but not unimportant contribution in some countries. In the case of D arnfieldi , donkeys are the prime source of pasture contamination for horses. Because transmission of infection to horses requires infected donkeys, first infections can occur at any age in that species. Once infected, adults become generally immune to further disease, but a proportion will contract subclinical infections during which they will act as a source of further larval contamination. In northern temperate areas in which cattle are housed during winter and first grazing season calves turned out in late April or May, the first infections can be seen between mid June and late July, but most severe infections develop after multiplication of a second generation of infective larvae between August and early October. Other Species—Because other lungworm species either require an intermediate host or are found in nonherd animals, disease caused by them is more sporadic. Metastrongylus apri in pigs requires the earthworm as intermediate host; thus, infection is confined to pigs with access to pasture. Muellerius capillaris and Protostrongylus rufescens in sheep and goats require slugs or snails as intermediate hosts, which must be eaten for infection to occur. Aelurostrongylus abstrusus is normally transferred to cats after ingestion of a paratenic host such as a bird or rodent that has previously eaten the slug or snail. Adults of Filaroides osleri live in nodules in the trachea of dogs, and larvated eggs laid by adults hatch there. Pups become infected from saliva or feces of an infected dog, in the former case by being licked by their dams. Capillaria aerophila in cats has a direct cycle, with infected eggs being ingested with food or water. Pathogenesis: The pathogenic effect of lungworms depends on their location within the respiratory tract, the number of infective larvae ingested, and the animal's immune state. During the prepatent phase of D viviparus infection, the main lesion is blockage of bronchioles by an infiltrate of eosinophils in response to the developing larvae; this results in obstruction of the airways and collapse of alveoli distal to the block. The clinical signs are moderate unless large numbers of larvae are present, in which case the animal may die in the prepatent phase with severe interstitial emphysema. In the patent phase, the adults in the segmental and lobar bronchi cause a bronchitis, with eosinophils, plasma cells, and lymphocytes in the bronchial wall; a cellular exudate, frothy mucus, and adult nematodes are found in the lumen. The bronchial irritation causes marked coughing, and the entire reaction leads to increased airway resistance. Interstitial emphysema, pulmonary edema, and secondary bacterial infection are complications that increase the likelihood of death. Survivors may suffer considerable weight loss. The lesions in pigs with M apri are a combination of localized bronchitis and bronchiolitis with overinflation of related alveoli, usually at the edges of the caudal lobes. In pigs, hypertrophy and hyperplasia of bronchiolar and alveolar duct smooth muscle with marked mucous cell hyperplasia are striking features. Near the end of the patent period (as the adult worms are killed), gray lymphoid nodules (2-4 mm) are formed; fragments of dead worms may be found microscopically in these nodules. In M capillaris and P rufescens infections, chronic, eosinophilic, granulomatous pneumonia seems to predominate; the reaction is in the bronchioles and alveoli that contain the parasites, their eggs, or larvae. They are surrounded by macrophages, giant cells, eosinophils, and other immunoinflammatory cells, which produce gray or beige plaques (1-2 cm) subpleurally in the dorsal border of the caudal lung lobes. In cats, A abstrusus produces nodular areas of granulomatous pneumonia in the caudal lobes that, if sufficiently generalized, can be clinically significant and occasionally fatal; a notable feature is the hypertrophy and hyperplasia of the smooth muscle in the media of pulmonary arteries and arterioles. The nodules of F osleri , found in the mucous membrane of the trachea and large bronchi, can produce extreme airway irritation and persistent coughing. Capillaria aerophila infection causes chronic tracheitis and bronchitis. Larvae that are not killed in the terminal bronchioles may reach the bronchi and cause a bronchitis characterized by marked eosinophilic infiltration of the bronchial walls and greenish yellow exudate in the lumen comprising eosinophils, other inflammatory cells, and parasitic debris. The reaction associated with this process can lead to severe clinical signs if the nodules are numerous and the eosinophilic bronchitis extensive; this is responsible for the reinfection phenomenon. Clinical Findings: Signs of lungworm infection range from moderate coughing with slightly increased respiratory rates to severe persistent coughing and respiratory distress and even failure. Reduced weight gains, reduced milk yields, and weight loss accompany many infections in cattle, sheep, and goats. Patent subclinical infections can occur in all species. The most consistent signs in cattle are tachypnea and coughing. Initially, rapid, shallow breathing is accompanied by a cough that is exacerbated by exercise. Respiratory difficulty may ensue, and heavily infected animals stand with their heads stretched forward and mouths open, and drool. Abnormal lung sounds are heard over the caudal lobes. The main clinical sign of M apri in pigs is a persistent cough that may become paroxysmal. Diagnosis: Diagnosis is based on the clinical signs, epidemiology, presence of first-stage larvae in feces, and necropsy of animals in the same herd or flock. Bronchoscopy and radiography may be helpful. Bronchial lavage can reveal D arnfieldi infections in horses. A convenient method for recovering larvae is a modification of the Baermann technique in which feces (25 g) are wrapped in tissue paper or cheese cloth and suspended or

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placed in water contained in a beaker. The water at the bottom of the beaker is examined for larvae after 4 hr; in heavy infections, larvae may be present within 30 min. In domestic pets and horses, because of the relative infrequency of infection, diagnosis may be made only after failure of antibiotic therapy to ameliorate the condition. Adults of Dictyocaulus spp and M apri are readily visible in the bronchi during the patent phases of infection. Bronchoscopy can be used to detect nodules of F osleri or to collect tracheal washings (dogs and horses) to examine for eggs, larvae, and eosinophils. Treatment: Several drugs are useful. Levamisole, the benzimidazoles (fenbendazole, oxfendazole, and albendazole), and ivermectin are frequently used in cattle and are effective against all stages of D viviparus . These drugs are also effective against lungworms in sheep, horses, and pigs. Fenbendazole has been used successfully in cats for A abstrusus . Filaroides osleri in dogs is a problem, but there is evidence that fenbendazole and albendazole are effective if treatment is prolonged. Control: Lungworm infections in herds or flocks are controlled primarily by vaccination or anthelmintics. Oral vaccines are available in Europe for D viviparus (northeastern areas) and D filaria (southeast). Necrobacillosis: Introduction The term necrobacillosis is used to describe any disease or lesion with which Fusobacterium necrophorum ( Sphaerophorus necrophorus ) is associated. It includes calf diphtheria, necrotic rhinitis of pigs, footrot of cattle, foot abscess of sheep, postparturient necrosis of the vagina and uterus, focal necrosis of the liver of cattle and sheep, quittor of horses, and numerous other necrotic lesions in ruminants and (less commonly) pigs, horses, fowl, and rabbits. The organism is probably a secondary invader rather than a primary cause and is usually part of a mixed infection. However, its necrotizing exotoxin undoubtedly plays a role in the production of characteristic lesions. It is part of the normal flora of the mouth, intestine, and genital tract of many herbivores and omnivores and is widespread in the environment. It is thought to gain entry to the body through wounds in the skin or mucous membranes. Calf Diphtheria (Necrotic laryngitis, Laryngeal necrobacillosis) Calf diphtheria is a disease of young cattle characterized by fever, inspiratory dyspnea, and stertorous breathing. Inflammation of the laryngeal mucosa and cartilage, caused by invasion of F necrophorum into laryngeal contact ulcers, is responsible for the clinical signs. Calf diphtheria primarily affects feedlot cattle between 3 and 18 mo of age; however, cases in calves as young as 5 wk and in cattle as old as 24 mo have been documented. Necrotic laryngitis has a worldwide distribution. Etiology: The primary etiologic agent is uncertain because F necrophorum , which is commonly isolated from lesions of affected cattle, is unable to penetrate intact mucous membranes. Transmission, Epidemiology, and Pathogenesis: Necrotic laryngitis is most common where cattle are housed in dirty environments or in feedlots. Clinical Findings: Initially, a moist, painful cough is noticed. Severe inspiratory dyspnea, characterized by open-mouth breathing with the head and neck extended and loud inspiratory stridor are common findings. Ptyalism; frequent, painful swallowing motions; bilateral, purulent nasal discharge; and a fetid odor to the breath may also be present. Systemic signs may include pyrexia (106°F [41.1°C]), anorexia, depression, and hyperemia of the mucous membranes. Untreated calves die in 2-7 days from toxemia and upper airway obstruction. Long-term sequelae include aspiration pneumonia and permanent distortion of the larynx. Lesions: Lesions are typically located over the vocal processes and medial angles of arytenoid cartilages. Acute lesions are characterized by edema and hyperemia surrounding a necrotic ulcer in the laryngeal mucosa; lesions may spread along the vocal folds and processes to involve the cricoarytenoideus dorsalis muscle. In chronic cases, lesions consist of necrotic cartilage associated with a draining tract surrounded by granulation tissue. Diagnosis: Clinical signs are usually sufficient to establish a diagnosis. However, because numerous other conditions can cause signs of upper airway obstruction, the larynx should be visually inspected to confirm a diagnosis. Differential diagnoses include pharyngeal trauma; severe viral laryngitis (eg, infectious bovine rhinotracheitis); actinobacillosis; and laryngeal edema, abscesses, trauma, paralysis, or tumors. Treatment and Control:

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Sulfonamides (an initial dose of 140 mg/kg, IV, followed by 70 mg/kg, IV, s.i.d.) or procaine penicillin (22,000 u/kg, IM, b.i.d.) are the drugs of choice. Nonsteroidal anti-inflammatory drugs (aspirin, 100 mg/kg, PO, b.i.d., or flunixin meglumine, 0.5-1.1 mg/kg, IM or IV, b.i.d.) can be used to decrease the degree of laryngeal inflammation and edema. A tracheostomy is indicated in cattle with severe inspiratory dyspnea. The prognosis is good for early cases that are treated aggressively; chronic cases will require surgery under general anesthesia to remove necrotic or granulation tissue and to drain laryngeal abscesses. There are no specific control measures for necrotic laryngitis. Bovine Respiratory Disease Complex: Overview Respiratory disease is among the most economically important diseases of cattle in production on a worldwide basis. Bovine respiratory disease (BRD) has a multifactorial etiology and develops as a result of complex interactions between environmental factors, host factors, and pathogens. Environmental factors (eg, weaning, transport, commingling, crowding, and inadequate ventilation) serve as stressors that adversely affect the immune and nonimmune defense mechanisms of the host. Parainfluenza-3 Virus (PI-3) Etiology: Parainfluenza-3 virus (PI-3) is an RNA virus classified in the paramyxovirus family. Infections caused by PI-3 are common in cattle. Although PI-3 is capable of causing disease, it is usually associated with mild to subclinical infections. The most important role of PI-3 is to serve as an initiator that can lead to the development of secondary bacterial pneumonia. Clinical Findings: Clinical signs include pyrexia, cough, serous nasal and lacrimal discharge, increased respiratory rate, and increased breath sounds. The severity of signs worsen with the onset of bacterial pneumonia. Lesions: Fatalities from uncomplicated PI-3 pneumonia are rare. Lesions include cranioventral lung consolidation, bronchiolitis, and alveolitis with marked congestion and hemorrhage. Inclusion bodies may be identified. Most fatal cases will also have a concurrent bacterial bronchopneumonia. Diagnosis: Diagnostic procedures for PI-3 are similar to those for bovine respiratory syncytial virus (see Bovine Respiratory Syncytial Virus (BRSV) ). Treatment and Prevention: Treatment focuses on the antimicrobial therapy directed toward bacterial pneumonia (see Pneumonic Pasteurellosis). Nonsteroidal anti-inflammatory drugs are also a therapeutic consideration. PI-3 vaccines are available and are almost always combined with bovine herpesvirus 1 (infectious bovine rhinotracheitis). Modified live and inactivated vaccines are available for IM administration. Vaccines containing temperature-sensitive mutants for intranasal administration are also available. Bovine Respiratory Syncytial Virus (BRSV) Etiology: BRSV is an RNA virus classified as a pneumovirus in the paramyxovirus family. In additional to cattle, sheep and goats can also be infected by respiratory syncytial viruses. Human respiratory syncytial virus (HRSV) is an important respiratory pathogen in infants and young children. This virus was named for its characteristic cytopathic effect—the formation of syncytial cells. BRSV infections associated with respiratory disease occur predominantly in young beef and dairy cattle. Passively derived immunity does not appear to prevent BRSV infections but will reduce the severity of disease. Initial exposures to the virus are associated with severe respiratory disease; subsequent exposures result in mild to subclinical disease. BRSV appears to be an important virus in the bovine respiratory disease complex because of its frequency of occurrence, predilection for the lower respiratory tract, and its ability to predispose the respiratory tract to secondary bacterial infection. Clinical Findings: Respiratory signs predominate. Signs include increased rectal temperature (104-108°F [40-42°C]), depression, decreased feed intake, increased respiratory rate, cough, and nasal and lacrimal discharge. Dyspnea may become pronounced in the later stages of the disease. Subcutaneous emphysema is sometimes reported. Secondary bacterial pneumonia is a frequent occurrence. A biphasic disease pattern has been described but is not consistent. Lesions: Gross lesions include a diffuse interstitial pneumonia with subpleural and interstitial emphysema along with interstitial edema. These lesions are similar to and must be differentiated from other causes of interstitial pneumonia. See also atypical interstitial pneumonia . Bronchopneumonia of bacterial origin is usually present. Merck Veterinary Manual - Summary

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Histologic examination reveals syncytial cells in bronchiolar epithelium and lung parenchyma, intracytoplasmic inclusion bodies, proliferation and/or degeneration of bronchiolar epithelium, alveolar epithelialization, edema, and hyaline membrane formation. Diagnosis: A diagnosis of BRSV requires laboratory confirmation. Paired serum samples can be used to establish a diagnosis of BRSV infection. However, the antibody titer of animals with well-developed clinical disease may be higher in the acute sample than in the sample taken 2-3 wk later. This is because the antibody response often develops rapidly, and clinical signs follow virus infection by up to 7-10 days. Treatment and Prevention: Treatment focuses on antimicrobial therapy to control secondary bacterial pneumonia (see Pneumonic Pasteurellosis). Nonsteroidal anti-inflammatory drugs may provide therapeutic benefit. Supportive therapy and correction of dehydration may be necessary. Bovine Herpesvirus 1 (BHV-1) (Infectious bovine rhinotracheitis virus, Infectious pustular vulvovaginitis, and associated diseases) Etiology and Epidemiology: Bovine Herpesvirus (BHV-1) is associated with several diseases in cattle: infectious bovine rhinotracheitis (IBR), infectious pustular vulvovaginitis (IPV), balanoposthitis, conjunctivitis, abortion, encephalomyelitis, and mastitis. Only a single serotype of BHV-1 is recognized; however, three subtypes of BHV-1 have been described on the basis of endonuclease cleavage patterns of viral DNA. These types are referred to as BHV-1.1 (respiratory subtype), BHV-1.2 (genital subtype), and BHV-1.3 (encephalitic subtype). Recently, BHV-1.3 has been reclassified as a distinct herpesvirus designated BHV-5. BHV-1 infections are widespread in the cattle population. In feedlot cattle, the respiratory form is most common. The viral infection alone is not life-threatening but predisposes to secondary bacterial pneumonia, which may result in death. In breeding cattle, abortion or genital infections are more common. Genital infections can occur in bulls (infectious pustular balanoposthitis) and cows (IPV) within 1-3 days of mating or close contact with an infected animal. Cattle with latent BHV1 infections generally show no clinical signs when the virus is reactivated, but they do serve as a source of infection for other susceptible animals and thus perpetuate the disease. Clinical Findings: The incubation period for the respiratory and genital forms is 2-6 days. In the respiratory form, clinical signs range from mild to severe, depending on the presence of secondary bacterial pneumonia. Clinical signs include pyrexia, anorexia, coughing, excessive salivation, nasal discharge that progresses from serous to mucopurulent, conjunctivitis with lacrimal discharge, inflamed nares (hence the common name “red nose”), and dyspnea if the larynx becomes occluded with purulent material. Pustules may develop on the nasal mucosa and later form diphtheritic plaques. Conjunctivitis with corneal opacity may develop as the only manifestation of BHV-1 infection. In the absence of bacterial pneumonia, recovery generally occurs 4-5 days after the onset of signs. Abortions may occur concurrently with respiratory disease but can occur up to 100 days after infection. In genital infections of cows, the first signs are frequent urination, elevation of the tailhead, and a mild vaginal discharge. The vulva is swollen, and small papules, then erosions and ulcers, are present on the mucosal surface. If secondary bacterial infections do not occur, animals recover in 10-14 days. If bacterial infection occurs, there may be inflammation of the uterus and transient infertility, with purulent vaginal discharge for several weeks. In bulls, similar lesions occur on the penis and prepuce. (See also Vulvitis And Vaginitis In Large Animals: Introduction .) BHV-1 infection can be severe in young calves and cause a generalized disease. Pyrexia, ocular and nasal discharges, respiratory distress, diarrhea, incoordination, and eventually convulsions and death may occur in a short period after generalized viral infection. Lesions: IBR is rarely fatal in cattle unless complicated by bacterial pneumonia. In uncomplicated IBR infections, most lesions are restricted to the upper respiratory tract and trachea. Petechial to ecchymotic hemorrhages may be found in the mucous membranes of the nasal cavity and the paranasal sinuses. Focal areas of necrosis develop in the nose, pharynx, larynx, and trachea. The lesions may coalesce to form plaques. The sinuses are often filled with a serous or serofibrinous exudate. As the disease progresses, the pharynx becomes covered with a serofibrinous exudate, and blood-tinged fluid may be found in the trachea. The pharyngeal and pulmonary lymph nodes may be acutely swollen and hemorrhagic. The tracheitis may extend into the bronchi and bronchioles; when this occurs, epithelium is sloughed in the airways. The viral lesions are often masked by secondary bacterial infections. Diagnosis: Uncomplicated BHV-1 infections can be diagnosed on the characteristic signs and lesions. However, because the severity of disease can vary, it is best to differentiate BHV-1 from other viral infections by viral isolation. Treatment and Control: Merck Veterinary Manual - Summary

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Antimicrobial therapy is indicated to prevent or treat secondary bacterial pneumonia. Both IM and intranasal modified live vaccines are available, but the IM types may cause abortion in pregnant cattle. The intranasal vaccines are more highly attenuated and, therefore, are recommended for use in breeding herds, including pregnant cows. The IM vaccines are easier to use and often are the vaccines of choice in feedlots. Bovine Viral Diarrhea Virus Bovine viral diarrhea virus (BVDV) is an RNA virus classified as a Pestivirus in the family Flaviviridae. BVDV is frequently isolated from cattle with shipping fever pneumonia, and a synergistic interaction has been demonstrated between this virus and Pasteurella haemolytica . Seroconversion The role of BVDV in BRD appears to be that of a virus capable of inducing immunosuppression, which allows for the development of secondary bacterial pneumonia. Treatment for BVDV infection is supportive and would include antimicrobials to prevent or treat bacterial pneumonia. General principles of control are discussed under enzootic pneumonia of calves and shipping fever pneumonia. Inactivated and modified live vaccines are available for IM administration. Modified live vaccines can induce immunosuppression and should be used with caution in highly stressed cattle. Pneumonic Pasteurellosis Etiology: Pasteurella haemolytica biotype A, serotype 1 is the bacterium most frequently isolated from the lungs of cattle with BRD. Although less frequently cultured than P haemolytica , P multocida is also an important cause of bacterial pneumonia. Haemophilus somnus is being increasingly recognized as an important pathogen in BRD; these bacteria are normal inhabitants of the nasopharynx of cattle (see also Haemophilus Somnus Disease complex: Introduction ). When pulmonary abscessation occurs, generally in association with chronic pneumonia, Actinomyces pyogenes is frequently isolated. The increased bacterial growth rate and colonization of the lungs may be due to suppression of the host's defense mechanism related to environmental stressors or viral infections. It is during this log phase of growth that virulence factors are elaborated by P haemolytica , such as an exotoxin that has been referred to as leukotoxin. The interaction between the virulence factors of the bacteria and host defenses results in tissue damage and development of pneumonia. Clinical Findings: Clinical signs of bacterial pneumonia are often preceded by signs of viral infection of the respiratory tract. With the onset of bacterial pneumonia, the severity of clinical signs increases and are characterized by depression and toxemia. There will be pyrexia (104-106°F [40-41°C]); serous to mucopurulent nasal discharge; moist cough; and a rapid, shallow respiratory rate. Auscultation of the cranioventral lung field reveals increased bronchial sounds, crackles, and wheezes. In severe cases, pleurisy may develop, which is characterized by an irregular breathing pattern and grunting on expiration. The animal will become unthrifty in appearance if the pneumonia becomes chronic, which is usually associated with the formation of pulmonary abscesses. Lesions: Pasteurella haemolytica causes a severe, acute fibrinous pneumonia or fibrinonecrotic pneumonia. The pneumonia has a bronchopneumonic pattern. Grossly, there is extensive reddish black to grayish brown cranioventral regions of consolidation with gelatinous thickening of interlobular septa and fibrinous pleuritis. There are extensive thromboses, foci of lung necrosis, and limited evidence of bronchitis and bronchiolitis. Pasteurella multocida is associated with a less fulminating fibrinous to fibrinopurulent bronchopneumonia. In contrast to P haemolytica , P multocida is associated with only small amounts of fibrin exudation, some thromboses, limited lung necrosis, and suppurative bronchitis and bronchiolitis. Haemophilus somnus infection of the lungs results in purulent bronchopneumonia that may be followed by septicemia and infection of multiple organs. Occasionally, H somnus is associated with extensive pleuritis. Pulmonary abscessation can occur as the pneumonia becomes chronic. Abscesses develop in ~3 wk but do not become encapsulated until 4 wk. Actinomyces pyogenes is frequently cultured from these abscesses. Diagnosis: Generally, neither serologic testing nor direct means of detection of bacteria are performed, and diagnosis relies on bacterial culture. Treatment: Early recognition and treatment with antibiotics is essential for successful therapy. It is important that antibiotic therapy extend beyond apparent recovery to avoid relapses. Mass medication in feed or water generally is of limited value because sick animals do not eat or drink enough to achieve inhibitory blood levels of the antibiotic. If pulmonary abscessation has occurred, it is difficult to achieve resolution with antimicrobials, and culling of the animal should be considered. Mycoplasmal Pneumonia Mycoplasmas are sensitive to several antibiotics, including the tetracyclines and macrolides.

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Toxic Gases Nitrogen dioxide is a major component of silo gas; in man, the disease is associated with exposure to NO2 is termed silo filler's disease. Exposure of cattle results in respiratory distress and necropsy findings of atypical interstitial pneumonia. Treatment is empirical and includes diuretics, corticosteroids, and antibiotics to prevent pneumonia. Zinc oxide is produced during oxyacetylene cutting or arc welding of galvanized pipes. These activities in closed facilities in which cattle are housed may result in toxicity characterized by respiratory distress. Lesions are similar to those described for atypical interstitial pneumonia. Treatment is as described for nitrogen dioxide toxicity. Respiratory Diseases Of Horses: Introduction A number of viruses affect the equine respiratory tract, notably the influenza, herpes, rhino, reo, and arteritis viruses. Adenovirus pneumonia has also been reported in association with combined immunodeficiency in Arabian foals. The significance of parainfluenza is obscure. Equine herpesvirus type 4 (EHV-4, rhinopneumonitis) and influenza are commonly involved in clinical infections. Equine herpesvirus type 1 (EHV-1) is primarily associated with abortion but is recognized as an occasional cause of respiratory disease. Viral respiratory infections usually produce pyrexia, nasal discharge, and frequently a cough. Sometimes, respiratory rate is increased. Secondary bacterial infections, which produce a mucopurulent nasal discharge and exacerbate the cough, are not uncommon. Affected horses usually look “sick” and are anorectic. Viral respiratory infections may affect all parts of the airway, including the paranasal sinuses and guttural pouches; therefore, it is incorrect to refer to them as upper respiratory tract viruses. Many bacteria and fungi can be isolated from the upper respiratory tract of normal horses. Streptococcus equi zooepidemicus is probably the most common, although Actinobacillus equuli , Bordetella bronchiseptica , Escherichia coli , Pasteurella spp , and Pseudomonas aeruginosa have also been isolated. Isolation of S equi equi indicates strangles ( Strangles). Recently, S pneumoniae has been identified from racehorses with bronchiolitis. Streptococcus spp are probably the most common organisms isolated from foals with pneumonia or pulmonary abscesses. However, Rhodococcus (Corynebacterium) equi infection produces a severe pneumonia and may be endemic on some farms. Respiratory infections may predispose to irritant or allergic bronchiolitis if affected horses are exposed to pollution by stable dusts. Vaccines of variable effectiveness are available for equine influenza, viral rhinopneumonitis, and strangles. Equine Herpesvirus 1 Infection: Overview (Equine viral rhinopneumonitis, Equine abortion virus) Etiology and Epidemiology: Equine herpesvirus 1 (EHV-1) and EHV-4 comprise two genetically and antigenically distinct groups of viruses that have at times been referred to as subtypes 1 and 2 of EHV-1. Both viruses are ubiquitous in horse populations worldwide. Each produces an acute febrile respiratory disease on primary infection, characterized by rhinopharyngitis and tracheobronchitis. Outbreaks of respiratory disease occur annually among foals in areas with concentrated horse populations; elsewhere, episodes are sporadic. Most of these outbreaks in weanlings are caused by strains of EHV-4. The age, seasonal, and geographic distributions vary and probably are determined by immune status and concentration of horses. In individual horses, the outcome of exposure is determined by viral strain involved, immune status, pregnancy status, and possibly age. Infection of pregnant mares with EHV-4 strains rarely results in abortion. Mares may abort several wk to mo after clinical disease or, in most instances, after subclinical infection with EHV-1. A further infrequent clinical sequela of EHV-1 infection, which is caused solely by certain 1 strains of EHV-1, is development of neurologic disease. The natural reservoir of both EHV-1 and EHV-4 is the horse. There is increasing evidence of latent carriers of both virus types. Transmission occurs by direct or indirect contact with infective nasal discharges, aborted fetuses, placentas, or placental fluids. Clinical Findings: After an incubation period of 2-10 days, susceptible horses may develop any of the following signs: fever of 102-107°F (39-42°C) that persists for 1-7 days, neutropenia and lymphopenia, congestion and serous discharge from nasal mucosa and conjunctiva, malaise, pharyngitis, cough, inappetence, and sometimes edematous mandibular or retropharyngeal lymph nodes, or constipation followed by diarrhea. Horses infected with EHV-1 strains often develop a diphasic fever, with the viremia coinciding with the second temperature peak. Secondary bacterial infections are common, with resultant mucopurulent nasal exudate and coughing. The infection is mild or inapparent in horses previously exposed and immunologically sensitized to the virus. Mares that abort after infection with EHV-1 seldom display any premonitory signs. Abortions occur 2-12 wk after infection, usually between mo 7 and 11 of gestation. Aborted fetuses are fresh or minimally autolyzed, and the placenta is expelled shortly after abortion. There is no evidence of damage to the mare's reproductive tract, and subsequent conception is unimpaired. Merck Veterinary Manual - Summary

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Infrequently, EHV-1 has been associated with development of herpetic lesions on the external genitalia of mares. Some horses in certain outbreaks of EHV-1 infection develop neurologic disease of varying clinical severity. Depending on the location and extent of the lesions, signs vary from mild incoordination and posterior paresis to severe posterior paralysis with recumbency, loss of bladder and tail function, and loss of sensation to the skin in the perineal and inguinal areas, and even the hindlimbs. In exceptional cases, the paralysis may be progressive and culminate in quadriplegia and death. Neurologic disease associated with EHV-1 is thought to occur more commonly in mares after abortion storms but has also been reported in barren mares, stallions, geldings, and foals after an outbreak of EHV-1 respiratory infection. Diagnosis: Equine viral rhinopneumonitis cannot be clinically differentiated from equine influenza (see Equine Influenza), equine viral arteritis ( Equine Viral Arteritis: Introduction), or certain other equine respiratory infections solely on the basis of clinical signs. Confirmation can be achieved by virus isolation, preferably from nasopharyngeal swabs and citrated blood samples taken very early in the course of the infection and by serologic testing of acute and convalescent sera. Diagnosis depends on demonstration of the characteristic vascular lesions in sections of CNS tissue of horses that die or are destroyed. Otherwise, the diagnosis tends to be presumptively based on clinical signs and on protein concentrations of the CSF. Treatment: There is no specific treatment. Rest during the acute febrile phase of respiratory disease caused by EHV-4 and several days thereafter is indicated to minimize secondary bacterial complications. If horses with EHV-1-associated neurologic disease are nonrecumbent, or recumbent for only 2-3 days, the prognosis is usually favorable. Control: Immunity after natural infection with either EHV-1 or EHV-4 appears to involve a combination of both humoral and cellular immune factors. Immunity to infection that leads to abortion seems to be related to the level of resistance at the pharyngeal lymphatic ring. Diminished resistance may lead to development of a leukocyte-associated viremia, which in turn may result in transplacental infection of the fetus. An inactivated vaccine is the only product currently recommended by the manufacturer as an aid in prevention of EHV1 abortion. It should be administered during months 5, 7, and 9 of pregnancy. Reliable humoral immunity produced by available vaccines against EHV-1 and EHV-4 generally persists for only 2-4 mo. Equine Influenza Etiology and Epidemiology: Equine influenza causes an acute, highly contagious, febrile respiratory disease. Two immunologically distinct influenza viruses have been found in horse populations worldwide except in Australia and New Zealand. The clinical outcome after viral exposure largely depends on immune status; in susceptible animals, this may vary from a mild, inapparent infection to severe disease that is rarely fatal except in young, old, or otherwise debilitated horses and in donkeys. Transmission occurs by the respiratory route through contact with infective respiratory secretions. Clinical Findings and Lesions: The incubation period is usually 1-3 days but ranges from 18 hr to 5 or, rarely, 7 days. Onset is abrupt, with fever up to 107.5°F (42°C) that usually lasts 7 minimizes renal ammonia production. If normal dog food is fed, urine alkalinization can be achieved by administering NaHCO3, 1 g (¼ tsp)/5 kg, PO, t.i.d., with food. If a very low protein prescription diet is fed, the urine pH is typically alkaline due to the presence of potassium citrate in the diet. Urine volume should be increased to reduce the concentration of all dissolved solutes in urine. This can be achieved by adding salt, 1 g (¼ tsp)/5 kg, daily to the diet, or by mixing water with the food. Prevention Protocol: The aim of prevention strategies is to reduce the concentration of ammonium and urate in urine to levels unlikely to induce flocculation. Treatment with allopurinol (10 mg/kg, PO, s.i.d.) can be considered. Cystine Stones: Stones composed almost entirely of cystine form in dogs with the renal tubular amino acid reabsorption defect known as cystinuria. Normal dogs demonstrate 97% fractional reabsorption of cystine, while affected dogs excrete a much greater proportion of the filtered cystine load and may even exhibit net cystine secretion. A unique characteristic of cystine is that it is the least soluble amino acid; therefore, it readily precipitates and forms stones. Despite excessive urinary loss of cystine in cystinuric dogs, plasma cystine levels remain the same as in normal dogs; in fact, the only morbidity or mortality associated with the inherited defect of cystine reabsorption is the sequela of urolith formation. Cystinuria is thought to be inherited as a sex-linked trait. The defect has been reported in Dachshunds, Basset Hounds, English Bulldogs, Chihuahuas, Yorkshire Terriers, Irish Terriers, and mixed breeds. Cystinuria has been recognized almost exclusively in male dogs. Cystine solubility depends on urine pH, with solubility increasing rapidly when urinary pH exceeds 7.5. Dogs fed meatbased diets tend to excrete acidic urine, which leads to urine cystine supersaturation. Cystinuria is a life-long defect of tubular reabsorption and cannot be cured. Cystine stones tend to recur within 1 yr if postdissolution management to prevent recurrence is not instituted, and they often recur despite attempts at prevention. Dissolution and Prevention Protocols: Urinary cystine output should be reduced. Protein-restricted alkalinizing diets (eg, Canine u/d®) have been associated with reducing the size of cystine urocystoliths. Urinary cystine concentration can also be reduced by administering tiopronin or penicillamine. Both tiopronin and penicillamine combine with cystine by exchange at the disulfide bridge to form an

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intermediate combination with cysteine that is many times more soluble than cystine. Unfortunately, ~40% of dogs treated with penicillamine exhibit anorexia and vomiting. The urine should be alkalinized to a pH>7.5. Sodium bicarbonate added to the diet at 1 g (¼ tsp)/5 kg, t.i.d., readily accomplishes this, but because sodium supplementation may enhance cystinuria, it is probably wiser to use potassium citrate instead. Potassium citrate tablets at a dose of 540 mg/10 kg, PO, b.i.d., or liquid at a dose of 1-1.5 mL/5 kg, PO, b.i.d., is an effective alkalinizing agent. Urine volume should be increased by mixing water with the food. Salt should not be added to the diet because increased sodium excretion may cause increased cystine excretion. Calcium Oxalate Stones: Calcium oxalate uroliths may develop in any breed, but Dalmatians, Lhasa Apsos, Miniature Schnauzers, Poodles, Shih Tzus, and Yorkshire Terriers are predisposed. Most affected dogs are 2-10 yr old. Hypercalciuria leading to calcium oxalate stone formation can result from increased renal clearance of calcium due to excessive intestinal absorption of calcium (absorptive hypercalciuria), to impaired renal conservation of calcium (renal leak hypercalciuria), or to excessive skeletal mobilization of calcium (resorptive hypercalciuria). Absorptive hypercalciuria is characterized by increased urine calcium excretion, normal serum calcium concentration, and normal or low serum parathormone concentration. Because absorptive hypercalciuria depends on dietary calcium, the amount of calcium excreted in the urine during fasting is normal or significantly reduced when compared with nonfasting levels. Renal leak hypercalciuria is recognized in dogs less frequently than is absorptive hypercalciuria. In dogs, renal leak hypercalciuria is characterized by normal serum calcium concentration, increased urine calcium excretion, and increased serum parathormone concentration. During fasting, these dogs do not show a decline in urinary calcium loss. The underlying cause of renal leak hypercalciuria in dogs is not known. Resorptive hypercalciuria is characterized by excessive filtration and excretion of calcium in urine as a result of hypercalcemia. Hypercalcemic disorders have only been infrequently associated with calcium oxalate uroliths in dogs. Treatment requires surgical removal followed by preventive strategies. Prevention Protocol: Previously, thiazide diuretics were recommended for reducing urinary calcium output; however, recent data have revealed that thiazide diuretics do not decrease urinary calcium output in dogs, and this strategy is no longer recommended. Intestinal calcium absorption should be reduced and, urinary calcium oxalate solubility should be increased. Alkalinizing agents may reduce GI calcium absorption by converting a greater percentage of ingested calcium into the nonionized form, which cannot be absorbed. Further, in alkaline urine, urinary citrate levels are increased and citrate inhibits stone formation by complexing with calcium ions and reducing calcium oxalate supersaturation. Potassium citrate may be the best alkalinizer for this purpose, but poor palatability often precludes its use. The currently recommended dose of potassium citrate is 150 mg/kg/day in 2-3 divided doses. Feeding a low-protein, reduced-calcium, alkalinizing diet (eg, Canine u/d ®) may also limit intestinal absorption of calcium and reduce urinary calcium excretion. Water consumption should be increased by adding water to the food or by flavoring the drinking water. Increased water consumption should not be induced by adding salt to the diet because increased sodium intake enhances hypercalciuria. Silicate Stones: Early reports indicated a predominance of silicate stones in German Shepherd Dogs, but many breeds have now been implicated. Urethral obstruction in males is the most common presenting problem. The mean age of occurrence is ~6 yr. The stones are usually multiple and in the bladder and urethra. Silicate uroliths are radiopaque. The calculi frequently, but not always, have a very characteristic “jack-stone” appearance. Only general management principles can be suggested for silicate urolithiasis. Additional salt should be administered in the diet to induce diuresis and to lower the urine solute concentration. When present, urinary tract infection should be eliminated. The effects of urine pH on silicate solubility are not established; therefore, no recommendation can be made concerning therapeutic alteration of urine pH. Feline Lower Urinary Tract Disease (FLUTD) and Feline Urolithiasis (Feline urologic syndrome, FUS) Hematuria, pollakiuria, and stranguria are the characteristic clinical signs of this common disease in cats. Feline urolithiasis is a common disease that occurs with equal frequency in both sexes. Most calculi in cats are small and resemble sand, but they may also occur as gelatinous plugs that differ from typical uroliths in that they contain a greater amount of organic matrix, which gives them a toothpaste-like consistency. Gelatinous plugs are most commonly found within the urethra near the urethral orifice and are primarily responsible for urethral obstruction. Urolithiasis is usually suspected based on clinical signs of hematuria, dysuria, or urethral obstruction. Urinalysis, urine culture, radiography, and ultrasonography may be required to differentiate uroliths from urinary tract infection or neoplasia. Radiography or ultrasonography are critically important to detect uroliths because only 10% of feline urocystoliths can be

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detected by abdominal palpation. Uroliths with a diameter >3 mm are usually radiodense; however, because smaller uroliths frequently occur, double contrast radiography may be required for detection. The most commonly encountered mineral in feline uroliths is struvite. Struvite Stones: Three distinct types of struvite uroliths are recognized in cats: amorphous urethral plugs with a large quantity of matrix, sterile struvite uroliths (which form perhaps as a result of certain dietary ingredients), and struvite uroliths that form as a sequela of urinary tract infection with urease-producing bacteria. Treatment of feline struvite urolithiasis focuses on eliminating bacterial infections of the urinary tract (if present), reducing the urine pH to ≤6.0, and reducing the urine magnesium concentration by feeding magnesium-restricted diets. Reducing urine pH and magnesium concentration is best accomplished by feeding a commercially available prescription diet formulated for this purpose. Calcium Oxalate Stones: The incidence of calcium oxalate uroliths in cats has recently increased, and they are the most common feline nephrolith, although their underlying cause is unknown. Common management schemes, which involve feeding diets with reduced magnesium, have reduced the incidence of feline struvite urolithiasis. Magnesium has been reported to be an inhibitor of calcium oxalate formation in rats and man; thus, the reduced magnesium concentration in feline urine may partially explain the increased occurrence of calcium oxalate stones in cats. Some calcium oxalate uroliths, especially those located in the kidneys, may not cause clinical signs for months to years. Current recommendations for prevention include feeding a nonacidifying diet restricted in protein and sodium (eg, Feline k/d® [Hill's]), eliminating any associated urinary tract infections, avoiding mineral and vitamin C supplementation, encouraging water consumption, and considering supplementation with vitamin B6 (2 mg/kg, PO, s.i.d.). The latter is thought to inhibit urinary oxalate excretion. Other Feline Stones: Ammonium urate, uric acid, calcium phosphate, calcium carbonate, and cystine uroliths are relatively rare in cats, but ammonium urate and uric acid account for ~6% of feline uroliths. Surgery remains the most reliable method to remove urate uroliths. Prevention should encompass consumption of diets that are low in purine precursors and promote formation of less acidic urine that is not highly concentrated. Although allopurinol may reduce the formation of urate in cats, studies of the efficacy and potential toxicity of allopurinol in cats are required before meaningful guidelines can be established.

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