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.
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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 <50,000/µL before the risk of hemorrhage increases. Thrombocytosis occurs only rarely and is often idiopathic. It may be associated with primary marrow disease such as in megakaryocytic leukemia. Thrombocytosis is often associated with chronic blood loss and iron deficiency because of increased platelet production in the marrow reacting to continued consumption and loss. Thrombocytopathies comprise a poorly defined group of diseases in which platelet numbers are normal, but their function is impaired. Von Willebrand's disease is characterized by both a plasma coagulation defect and a defect in platelet adhesion to the endothelium. Anemia: Introduction Anemia is a condition characterized by insufficient circulating hemoglobin (Hgb). It results from excessive red blood cell (RBC) destruction, RBC loss, or decreased RBC production. Anemias can be regenerative or nonregenerative (Table: Classification of Anemias). Regenerative anemias show evidence of response by the bone marrow to increase the number of circulating RBC. This response is measured by the quantity of reticulocytes (immature RBC) present in the circulation. Regenerative anemias have a high reticulocyte count and are due to RBC loss or destruction. In a nonregenerative anemia, the bone marrow responds poorly and the reticulocyte count is low. Anemias can also be acute or chronic. Most commonly, acute anemias are due to either RBC loss or destruction. Chronic anemias are usually due to lack of RBC production, although slow blood loss can also be a cause. RBC indices are used to further characterize and classify anemias. The mean corpuscular volume (MCV) is an indication of RBC size. The MCV (femtoliters) = (PCV × 10) ÷ RBC (millions). As RBC precursors mature in the bone marrow, their volume decreases as the Hgb content increases. Therefore, reticulocytes have a higher MCV, and the MCV is increased in regenerative anemias. An anemia with a high MCV is classified as a macrocytic anemia. RBC size is smaller than normal when iron is insufficient, which results in decreased quantities of Hgb and a decreased MCV. An anemia with a low MCV is classified as a microcytic anemia. A low MCV in an anemic adult animal indicates iron deficiency from a slow loss of blood (usually GI or renal). A low MCV is seen in the Akita and Shiba Inu, which normally have small RBC. A low MCV may be seen in some cases of congenital hepatic shunts. The mean corpuscular hemoglobin concentration (MCHC) indicates the concentration of hemoglobin per unit volume of RBC. The MCHC (g/dL) = (Hgb × 100) ÷ PCV. It provides similar information as the mean corpuscular hemoglobin (MCH) but is considered to be more accurate. The MCH (picograms) = (Hgb × 10) ÷ RBC (millions). A low MCHC accompanying macrocytosis is indicative of a regenerative anemia. Laboratory diagnosis of anemia is based on the Hgb concentration, the number of RBC, and the hematocrit or packed cell volume (PCV). The next essential test is the reticulocyte count. Reticulocytes are polychromatic cells when stained with Wright's stain or a Giemsa-type stain. The vital stain new methylene blue specifically stains reticulocytes. Reticulocytosis is first seen 72 hr after the onset of significant blood loss or hemolysis. Peak reticulocyte response occurs within 5-7 days. The reticulocyte index = animal's PCV × % reticulocytes ÷ normal PCV. A value >1 indicates an appropriate response.

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Spherocytes are seen in cases of immune-mediated hemolytic anemia. They are not discernible in cats because feline RBC normally lack central pallor. Nucleated RBC in the presence of adequate reticulocytosis indicates regeneration. In the absence of a reticulocyte response however, they indicate bone marrow or splenic disease. The presence of Heinz bodies indicates a Heinz body anemia. Up to 10% of feline RBC normally contain Heinz bodies. Basophilic stippling and nucleated RBC may be seen in lead poisoning, and RBC agglutination indicates immune-mediated disease. Thrombocytosis and neutrophilia are often seen in cases of regenerative anemia. The PCV and total protein are determined simultaneously because a decrease in both values is seen in cases of blood loss anemia. A normal total protein and decrease in the PCV is seen with hemolysis and anemias due to lack of RBC production. Signs of acute anemia include sudden onset of weakness, lethargy, acute collapse, pale mucous membranes, change in urine color, tachypnea, and dyspnea. Usually, RBC loss or hemolysis is the cause. Signs of chronic anemia are often vague and include lethargy, depression, and anorexia. The owner may note pale mucous membranes, weakness, and dyspnea. In many instances, these signs may appear to be of sudden onset to the owner. Chronic anemias, characterized by a slower onset of signs, are usually nonregenerative and associated with decreased RBC production. In all cases, owners should be questioned about possible drug or toxin exposure, as well as the possibility of a traumatic incident. Owner complaints referable to a particular body system may localize the problem to this area. Blood Loss Blood loss may be peracute, acute, or chronic, and the clinical signs depend on the rapidity of blood volume depletion. Chronic blood loss can result in iron deficiency, and a nonregenerative anemia develops. External parasitism may cause anemia, particularly in young animals. In general, bloodsucking insects such as Tabanidae, black flies, and mosquitoes cause more irritation than blood loss. Internal parasitism also may cause anemia. Hookworm infection may cause profound anemia in young dogs and cats ( Hookworms). Iron lost in intestinal parasitism is not reabsorbed; in chronic cases, response may be better to parenteral iron than to an anthelmintic. The marrow usually is productive if iron stores are not exhausted, and peripheral blood reticulocytosis is marked with occasional severe poikilocytosis. Diarrhea occurs with most GI parasitisms of sheep except Haemonchus . In calves and yearling cattle, chronic Ostertagia infection ( Haemonchus, Ostertagia, and Trichostrongylus spp) causes cachexia, an anemia with poor reticulocyte response, and occasionally marked poikilocytosis. Neoplasms with bleeding into body cavities or tissue planes or external bleeding may cause a blood loss anemia that is often peracute in nature. Initial treatment consists of volume expansion and RBC replacement when significant hemorrhage has occurred. Continued bleeding should be stopped, and the underlying disease condition treated. Excessive Rbc Destruction: Overview Hemolytic anemias may be extravascular or intravascular. Extravascular hemolysis occurs when the reticuloendothelial system phagocytizes RBC. Hgb is converted into bilirubin, resulting in icterus and bilirubinuria. When intravascular hemolysis occurs, RBC release Hgb into the blood vascular system, resulting in hemoglobinemia, hemoglobinuria, and, later, icterus. Direct and indirect bilirubin determinations are not extremely useful in hemolytic disease, except in the very early stages of disease. Indirect bilirubin has not yet been conjugated by the liver and is increased early on. The liver then conjugates bilirubin, and direct bilirubin levels rise. Because the liver can normally conjugate large amounts of bilirubin, a high indirect bilirubin in the presence of hemolytic disease and anemia indicates either severe hemolysis or concurrent liver disease. Extracorpuscular Abnormalities Immune-mediated Hemolytic Anemia (IHA): Immune-mediated hemolytic anemia is the accelerated destruction of RBC coated with antibody or antigen-antibody complexes adhered to the RBC surface. It is characterized by a regenerative anemia, spherocytosis (in dogs), and often the presence of autoantibodies against RBC (positive Coombs' test). Primary (idiopathic) IHA involves only the RBC themselves and accounts for 60-70% of cases in dogs. High concentrations of serum antibody to viral antigens in dogs with primary IHA suggest that idiopathic disease may follow viral infections. Secondary IHA is associated with a wide variety of underlying conditions. These include immune-mediated thrombocytopenia, systemic lupus erythematosus, viral disease, severe bacterial infection, granulomatous disease, lymphosarcoma, lymphocytic leukemia, and drug administration. Drugs associated with IHA include trimethoprim sulfa and ormetoprim sulfa in dogs and methimazole and propylthiouracil in cats.
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Animals with acute or chronic disease involving extravascular hemolysis may present with weakness, fever, anemia, and possibly jaundice. Many animals have splenomegaly because the spleen is usually primarily involved in the RBC destruction. rouleaux formation is not a sign of immune-mediated RBC destruction. Therapy for IHA is directed toward suppressing destruction of RBC by the reticuloendothelial system and decreasing production of destructive antibody. In cases of secondary IHA, underlying causes must be recognized and treated. Immunosuppressive dosages of corticosteroids (prednisone 2.2 mg/kg or dexamethasone 0.3 mg/kg) are administered to rapidly suppress the reticuloendothelial system. If corticosteroids are not effective, then other immunosuppressive drugs (eg, cyclophosphamide, azathioprine) are used. In addition to suppressing the reticuloendothelial system, these drugs decrease antibody production more rapidly than corticosteroids. These drugs are indicated in cases with severe autoagglutination, intravascular hemolysis, severe anemia most likely requiring transfusions, when a transfusion is administered, and when moderate to severe icterus is present. If transfusions are done, crossmatching is essential, and the animal should be observed closely for reactions. Splenectomy has not been shown to be effective for IHA in dogs. Isoimmune Hemolytic Disease of the Neonate: This occurs when the fetus has a blood type that is incompatible with that of the mother who has been previously sensitized with RBC, resulting in production of isoantibodies. The newborn animal receives the antibodies when ingesting colostrum. Of dogs, ~40% carry the DEA 1 antigen, and of cats, ~90% carry the A antigen. Hemolytic Disease of Newborn Calves: Spontaneous sensitization of cattle to fetal RBC antigens is rare or does not occur. Vaccines derived from blood and used to prevent babesiosis and anaplasmosis may contain RBC antigens that immunize the dams. If the bull has the same RBC antigens as the vaccine donor, then the calves may share these antigens and develop isoimmune hemolytic anemia when they receive colostrum. The Coombs' test usually is strongly positive. Owners may note red urine in newborn calves and exacerbate the problem by revaccinating dams on suspicion of neonatal infection. Blood usually is not transfused because of donor incompatability. A single transfusion from an unvaccinated cow, or transfusion of saline-washed (three times) packed RBC of the dam may be used to increase PCV to 25%. Antibiotics and steroids may be helpful. Hemolytic Disease of Newborn Foals: Affected foals are normal at birth but can absorb dangerous amounts of isoantibodies from colostrum through their GI tract for up to 36 hr. Clinically recognizable neonatal isoerythrolysis rarely occurs in foals of primiparous mares and generally is not seen until a mare has had her third or fourth foal. Although neonatal erythrolysis may occur in foals of any breed, it is more frequent in Thoroughbreds and mules. Signs may appear 8 hr to 5 days after birth. They include lethargy, jaundice, dyspnea, pounding heart, and in severe cases, hemoglobinuria. The foals spend much of their time lying down, and those severely affected often cannot stand. A positive Coombs' test in an anemic foal is strong presumptive evidence, and demonstration of specific antibody against foal RBC in maternal serum or colostrum is definitive. Splenomegaly and generalized icterus are often seen in foals dying 24-48 hr after birth. Blood transfusion is the only known method of saving a severely anemic foal. The whole blood of the dam or the sire cannot be used in transfusions because it contains the hemolytic antibody, but the saline-washed RBC of the mare probably is the treatment of choice. If the dam's RBC are available, two or three washes in isotonic saline solution are essential. An accompanying neutrophilic leukocytosis is present. The foal can be nursed by a normal foster mare or bottlefed on colostrum from nonimmunized mares. Such colostrum can be stored frozen for this purpose. The dam should be milked to remove most of her colostrum. The disease usually can be prevented by mating mares that have already produced one or more affected foals to stallions with RBC that are not agglutinated or hemolyzed by isoantibodies present in the mare's serum. Blood Groups And Blood Transfusions: Introduction Blood groups are determined by genetically controlled, polymorphic, antigenic components of the RBC membrane. Normally, an individual does not have antibodies against any of the antigens present on its own RBC or against other blood group antigens of that species' systems unless they have been induced by transfusion, pregnancy, or immunization. ~50% of dogs have a naturally occurring cold hemagglutinin, DEA 7 (DEA stands for Dog Erythrocytic Antigen). The number of major recognized blood group systems (see Table: Major Blood Groups of Clinical Interest ) varies among domestic species with cattle being the most complex and cats the most simple. Crossmatching The direct crossmatch procedure, with appropriate controls, is effective for all species. The major crossmatch detects antibodies already present in recipient plasma that could cause a hemolytic reaction when donor RBC are transfused.
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The minor crossmatch is the reverse of the major crossmatch, ie, recipient cells are combined with donor plasma. The minor crossmatch is important only in species with naturally occurring isoantibodies or if the donor has been previously transfused or, in horses, previously pregnant. Blood Transfusions Animals with hemostatic disorders often require repeated transfusions of either whole blood, red cells, plasma, or platelets. Blood transfusions must be given with care because they have the potential for further compromising the recipient. In horses and dogs, the blood group antigens most commonly implicated in transfusion incompatibilities are known; by selecting donor animals that lack these groups, the prevalence of recipient sensitization can be decreased. Previously sensitized recipients can be detected by crossmatching, which will preclude administration of incompatible blood. In the USA, >99% of cats are of blood group A, so the risk of incompatible transfusion is low. Any incompatible transfusion in cats results in rapid destruction of transfused cells. Whole blood frequently is not the ideal product to be administered. If the need is to replace the oxygen-carrying capability of the blood, then packed RBC are more appropriate; if replacement of circulatory volume is needed, crystalloid or colloid solutions may be used to replace volume, with packed RBC added as needed. Platelet numbers rise rapidly after hemorrhage, so replacement is not needed. Plasma proteins equilibrate from the interstitial space, so plasma is not needed except in massive hemorrhage (>1 blood volume in 24 hr). Animals that require coagulation factors benefit most from administration of fresh-frozen plasma or cryoprecipitate if the need is specifically for factor VIII, von Willebrands factor, or fibrinogen. Platelet-rich plasma or platelet concentrates may be of value in thrombocytopenia, although immune-mediated thrombocytopenia usually does not respond to administration of platelets because they are removed rapidly by the spleen. All domestic animals have blood volumes of ~7% of their body weight except cats, which have a blood volume of 4% of their body weight. By determining the recipient's blood volume and knowing the animal's PCV, the required replacement RBC volume can be calculated. For example, a 25-kg dog has a total blood volume of ~2,000 mL; with a PCV of 15%, the RBC volume is 300 mL; if the PCV is to be increased to 20%, that equals an RBC volume of 400 mL. Therefore, 100 mL of RBC or 200 mL of whole blood (with PCV of 50%) would be required to increase the recipient's PCV to the desired level. These calculations assume no ongoing losses of RBC through hemorrhage or hemolysis. No more than 25% of a donor animal's blood should be collected at one time. The anticoagulant of choice is citrate phosphate dextrose adenine (CPDA-1). Heparin should not be used as an anticoagulant because it has a longer half-life in the recipient and causes platelet activation; also, heparinized blood cannot be stored. Blood collected in CPDA-1 may be safely stored at 4°C for 3 wk. Risks of Transfusion: The most common hemolytic reaction in dogs that have received multiple transfusions is delayed hemolysis, seen clinically as shortened survival of transfused RBC and a positive Coombs' test. Repeated transfusions can cause acute hemolysis. Other complications include sepsis from contaminated blood, hypocalcemia from too much citrate, and hypervolemia (especially in animals with preexisting heart disease or in very small animals). Urticaria, fever, or vomiting are seen occasionally. Transfusions can also spread disease from donor to recipient, such as RBC parasites (eg, Haemobartonella , Anaplasma , or Babesia ) and viruses (eg, retroviruses such as feline or bovine leukemia, equine infectious anemia, or other slow viruses). Other diseases, such as those caused by rickettsia or other bacteria, can also be spread if the donor is bacteremic. Anaplasmosis Anaplasmosis, formerly known as gall sickness, is a disease of ruminants caused by obligate intraerythrocytic parasites of the order Rickettsiales, family Anaplasmataceae, genus Anaplasma . Anaplasmosis occurs in tropical and subtropical regions worldwide Transmission and Epidemiology: Anaplasmosis is not contagious. Most transmission occurs via numerous species of tick vectors. There is a strong correlation between age of cattle and severity of disease. Calves are much more resistant to disease (though not infection) than older cattle. This resistance is not due to colostral antibody from immune dams. After recovery from the acute phase of infection, cattle remain chronically infected carriers of the parasite and immune to further clinical disease. However, these chronically infected cattle may relapse to anaplasmosis when immunosuppressed (eg, by corticosteroids), when infected with other parasites, or after splenectomy. Carriers serve as a reservoir for further transmission. Clinical Findings: Anaplasmosis is characterized by progressive anemia due to extravascular destruction of infected and uninfected erythrocytes. Macrocytic anemia with circulating reticulocytes may be present late in the disease. There is moderate anisocytosis, slight polychromasia, and an increase in unconjugated bilirubin in the serum.

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The urine may be brown but, in contrast to babesiosis, hemoglobinuria does not occur. Mucous membranes appear pale and then yellow. Diagnosis: Anaplasma marginale , together with the hemoprotozoa Babesia bovis and B bigemina , are the causative agents of tick fever in cattle. Anaplasma marginale inclusions are usually located toward the margin of the infected erythrocyte, whereas A centrale inclusion bodies are located more centrally. Treatment: The tetracyclines and imidocarb are currently used for treatment. Injection into the neck muscle rather than the rump is preferred. Imidocarb is also highly efficacious against A marginale as a single injection. Imidocarb is a suspected carcinogen with long withholding periods and is not approved for use in the USA or Europe. Prevention: In some countries, infection with live A centrale is used as a vaccine to protect cattle against severe disease due to subsequent infection with the more pathogenic species A marginale . Anaplasma centrale vaccine produces severe reactions in a small proportion of cattle. Hemobartonellosis (Feline infectious anemia) Feline infectious anemia (FIA) is an acute or chronic disease of domestic cats, seen in many parts of the world, caused by a rickettsial agent that multiplies within the vascular system. Etiology, Transmission, and Pathogenesis: FIA is caused by an epicellular RBC rickettsial parasite, Haemobartonella felis (termed Eperythrozoon felis in Europe and Australia). It is gram-negative and nonacid-fast and reproduces by binary fission. The causative organisms are usually found in varying numbers on the surface of the RBC but are occasionally seen free in the plasma. Blood films should be examined daily for 5-10 days if infection with H felis is suspected because organisms are recognized in only 50% of cats in the acute phase of the disease. During the acute phase, numbers of H felis organisms increase gradually, then disappear rapidly; clearance of organisms may occur within 2 hrs. In chronically infected cats, organisms appear only sporadically and in small numbers. Intrauterine transmission can also occur, and infections can be transmitted iatrogenically via blood transfusions. However, the natural mode of transmission is believed to be via blood-sucking arthropods (such as fleas) and possibly via bite wounds. Incidence of the naturally occurring disease appears to be higher among 1- to 3-yr-old cats, particularly males. A significant portion of the feline population may carry the infection in a latent form, which becomes exacerbated during debilitating disease or stress. Underlying infection with feline leukemia or feline immunodeficiency virus should always be investigated in cats with hemobartonellosis. Immune-mediated mechanisms of RBC injury are also important in the pathogenesis of FIA. Parasitized RBC may be damaged by antibody-complement interactions against H felis antigens. In addition, parasite-induced exposure of hidden or altered RBC antigens may lead to RBC destruction; erythrophagocytosis by the reticuloendothelial system appears to be more important than intravascular hemolysis. Clinical Findings: Any anemic cat may be suspected of having FIA. In acute cases, there is usually a fever of 103-106°F (39-41°C); the temperature may drop to subnormal in moribund cats. The severity of clinical signs correlates with the rapidity of onset of anemia. Diagnosis: Laboratory confirmation depends on identification of the parasite in the peripheral blood or bone marrow. A series of smears stained with Wright-Giemsa stain over a period of several days may be required for an accurate diagnosis because the erythrocytic bodies exhibit periodicity. Certain artifacts such as Howell-Jolly bodies may be mistaken for blood parasites. The slides should be clean, and the stains should be filtered immediately before use because dirt particles and stain precipitates can mimic the appearance of the organism. In the southeastern USA, differentiation from feline cytauxzoonosis ( Cytauxzoonosis) should be made. Cytauxzoon felis appears as an intracellular ring, rod, or coccoid-shaped protozoan 0.5-2 mm in diameter within RBC, while H felis tends to form chains on the surface of RBC. Treatment: Severely dyspneic cats may require oxygen, and whole blood or packed RBC transfusions may be needed in cats with a PCV of ≤15%, particularly if the anemia is acute. Tetracycline (20 mg/kg, PO, t.i.d. for 21 days) is recommended as a specific antirickettsial agent. Doxycycline (10 mg/kg, PO, s.i.d. for 21 days) is also effective. Although chloramphenicol has also shown efficacy against H felis , it can cause a significant but reversible erythroid hypoplasia that may interfere with the regenerative response.
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Canine Malignant Lymphoma: Introduction (Lymphoma, Lymphosarcoma, Lymphocytic leukemia) Canine malignant lymphoma is a progressive, fatal disease characterized by neoplastic transformation and proliferation of lymphoid cells, usually originating in solid lymphoid organs (lymphosarcoma) or bone marrow (lymphocytic leukemia). The variable signs depend on which organs are involved. No viral etiology has been established in dogs, in contrast to most other domestic species. The disease is histologically and immunologically heterogeneous, and different morphologic subtypes may behave differently. It is the most common hematopoietic neoplasm of dogs (reported incidence 24:100,000). Clinical Findings: The most common early clinical sign is a painless, peripheral lymphadenopathy, often first noticed in lymph nodes about the throat and neck. Subsequently, nonspecific signs, including anorexia, weight loss, anemia, and inactivity develop gradually as neoplastic cells progressively infiltrate visceral organs. In the alimentary form, signs are associated with GI obstruction or malabsorption; 80% of affected dogs may have diarrhea and weight loss. Hypercalcemia may be seen in 10-40% of dogs with malignant lymphoma. There are 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 tumor cells; the other, probably more common, is humoral hypercalcemia in which neoplastic cells produce a substance that acts at a distance (see also hypercalcemia of malignancy, Hypercalcemia of Malignancy ). Dogs with hypercalcemia have polyuria and polydipsia or renal failure. Urinary excretion of calcium, phosphorus, and hydroxyproline is increased if there is hypercalcemia. Lesions: Commonly, all superficial and various internal lymph nodes are 3-10 times normal size (multicentric form). Diagnosis: True lymphocytic leukemia, which is characterized by a normal to increased WBC count with a predominance of lymphoid cells in peripheral blood and bone marrow is rare and must be differentiated from lymphosarcoma because of the different prognosis and response to therapy. Poorly differentiated, acute lymphoblastic leukemia is an aggressive disease with a poor prognosis, whereas well-differentiated, chronic lymphocytic leukemia is slowly progressive and responds relatively well to therapy. Most canine lymphomas are high-grade (blast cell), diffuse lymphosarcomas, although ~20% are low-grade (welldifferentiated). Dogs with high-grade tumors respond better to chemotherapy and have longer remission and survival times than those with low-grade lymphomas, which may have a more indolent course and do not respond as well to chemotherapy. The cell of origin is either the B- or T-cell lymphocyte, although some are of undetermined origin. Two separate studies have found that >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 <6 mo and a complete response rate of ~30%. Disseminated intravascular coagulation (DIC) is a syndrome characterized by massive activation and consumption of coagulation proteins, fibrinolytic proteins, and platelets. It is not a primary disease, but a disorder secondary to numerous triggering events such as bacterial, viral, rickettsial, protozoal, or parasitic diseases; heat stroke; burns; neoplasia; or severe trauma. In acute, fulminant DIC, the clinical presentation is uncontrolled hemorrhaging and the inability to form a normal clot. Classically, all coagulation screening tests (ACT, APTT, PT, thrombin time) are prolonged, fibrin (or fibrinogen) degradation products are increased, and fibrinogen and platelet concentrations are decreased. Death is caused by extensive microthrombosis or circulatory failure, leading to single or multiple organ failure. DIC can usually be identified by the presence of at least three abnormal coagulation test results. Horses, even in
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fulminant DIC, most often have hyperfibrinogenemia because their liver can produce much fibrinogen. Treatment should be directed toward correcting the underlying problem. Congenital Thrombocytopenia Fetal and neonatal alloimmune thrombocytopenia occurs when maternal antibodies are produced against a paternal antigen on fetal platelets. Caseous Lymphadenitis of Sheep and Goats This caseous abscessation of lymph nodes and internal organs caused by Corynebacterium pseudotuberculosis occurs worldwide. Etiology and Pathogenesis: Two biotypes have been identified: a nitrate-negative group that infects sheep and goats, and a nitrate-positive group that infects horses. Isolates from cattle are a heterogeneous group. All strains produce an antigenically similar exotoxin with enzymatic activity (phospholipase D[PLD]) that appears to be leukotoxic and that can damage endothelial cells and promote spread from the initial site of infection to regional lymph nodes and visceral organs. The chemical composition of its cell wall (high lipid content) enables the organism to resist being killed by phagocytes and to maintain chronic infection. The disease is commonly introduced into a flock by entry of an apparently healthy carrier from an infected flock, by contact on shared pastures, or via contaminated shearing equipment. Clinical Findings: Caseous lymphadenitis is a chronic, recurring disease. A slowly enlarging, localized, and nonpainful abscess may develop either at the point of entry into the skin or in the regional lymph node (superficial or external form), from which it may spread via the blood or lymphatic system and cause abscessation of internal lymph nodes or organs (visceral or internal form). Superficial abscesses enlarge and may rupture and discharge infectious pus. In sheep on range, most superficial abscesses develop in the prescapular and prefemoral region, with transmission probably occurring at shearing time. In housed goats and sheep, superficial abscesses develop mainly in the head and neck region due to transmission by contaminated feed, feeders, and other fomites. In sheep, the abscess often has the classically described laminated “onion-ring” appearance in cross section, with concentric fibrous layers separated by inspissated caseous exudate. In goats, the exudate is usually soft and pasty. Diagnosis: For definitive diagnosis, an aspirate of an abscess should be submitted for bacteriologic examination. Treatment and Control: Treatment is usually not attempted. Although the organism is susceptible to penicillin, the formation of abscesses limits the penetration and effectiveness of antibiotics. Therefore, prophylactic and therapeutic treatment will not eliminate C pseudotuberculosis from infected flocks or individuals. Abscesses frequently recur after draining or attempted surgical excision. Prevention is based on reducing transmission of the organism from infected to susceptible animals. Emaciated animals and those with recurrent abscesses should be culled. When animals are too valuable to cull, those with developing abscesses should be isolated, and the abscesses lanced and flushed with iodine solution. Commercial vaccines reduce the incidence and prevalence of caseous lymphadenitis within a flock but neither prevent all new infections nor cure animals already infected. Eradication is difficult and requires rigorous culling of all infected animals. Seropostive animals should not be accepted into the flock. Corynebacterium pseudotuberculosis Infection of Horses and Cattle In horses, C pseudotuberculosis causes ulcerative lymphangitis , an infection of the lower limbs, and chronic abscesses in the pectoral region and contagious acne. Pathogenesis and Clinical Findings: The onset of ulcerative lymphangitis is slow and usually manifests by painful inflammation, nodules, and ulcers, especially in the region of the fetlock; occasionally, the edematous swelling can extend up the entire limb. The exudate is odorless, thick, greenish white, and blood tinged. Usually, only one leg is involved. Unhygienic and wet conditions predispose animals to infection, particularly of the lower legs and ventral region. However, the disease also occurs under excellent management conditions. Diagnosis: Isolation of C pseudotuberculosis from lesions is necessary for confirmation. Differential diagnoses include pyoderma, abscesses, lymphangitis (caused by Staphylococcus aureus , Rhodococcus equi , Streptococcus , or Dermatophilus ), dermatophytosis, sporotrichosis, equine cryptococcosis, North American blastomycosis, and onchocerciasis.
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Treatment: Lymphangitis and early abscess swellings are treated with hot packs, poultices, or hydrotherapy. Abscesses are lanced and flushed with iodine solution. Cardiovascular System Introduction: Introduction Heart Rate and the Electrocardiogram: At rest, the SA node discharges ~15 times/min in the horse, >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
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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
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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
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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
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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 (<1 mV), and there may be a pattern of alternating heights of the R waves, referred to as electrical alternans. This electrocardiographic feature is virtually pathognomonic for pericardial effusion and results from the swinging motion of the heart within the fluid-filled pericardial sac. Animals with cardiac tamponade should receive urgent treatment. The only effective treatment is pericardiocentesis, ie, removing the effusion with a catheter. Cardiac medications have no role. Diuretics are contraindicated because they decrease blood volume and cause further collapse of the cardiac chambers. As much fluid as possible should be removed, and a sample placed into an EDTA tube for analysis. Medications are ineffective and contraindicated. Broad-spectrum antibiotics and parenteral fluids may be given immediately before and after pericardiocentesis. Heartworm Disease: Introduction (Dirofilariasis) Dirofilaria immitis has a worldwide distribution and infects a wide variety of species (dog, cat, ferret, fox, wolf, sea lion, horse). The distribution is influenced by a reservoir population of animals (dogs usually) in which the life cycle is completed and microfilaremia occurs and by a mosquito vector in which the early larval stages develop. Different mosquito feeding patterns influence the areas and species of animal infected. For transmission to cats, the mosquito must first feed on a dog and then, after adequate warm environmental exposure, feed on a cat. Life Cycle and Pathogenesis: Adult female (~27 cm long) and male (~17 cm long) heartworms normally reside in the pulmonary arteries and right ventricles without significantly interfering with blood supply. Microfilariae (~315 µm long and 6-7 µm wide) are discharged into the bloodstream and survive 1-3 yr. The number of circulating microfilariae in dogs is increased in warm ambient temperature, after eating, and late at night. The microfilariae are ingested by a mosquito during feeding. Within the mosquito, the larvae (L1) migrate to the stomach and then to the mouthparts (L3) during development. When the mosquito feeds again, the infective L3 are deposited on the skin of the animal and enter through the bite wound. The L3 stages molt and migrate to the pulmonary arteries ~100 days after infection, during which time they develop to L5 (1-2 cm long). The L5 are found mainly in the caudal distal pulmonary arteries; over the next 2-3 mo, they develop to mature adult heartworms and migrate back toward the right ventricle. If both sexes of adults are present, microfilariae are produced 6-7 mo after the animal was infected with L3. In endemic areas, the average worm burden is ~15 worms in dogs and 1-3 worms in cats. In cats and ferrets, respiratory failure can be associated with infection with a single worm. High worm burdens can be found in dogs with minimal cardiac changes if the dog is sedentary. Because many animals develop increased resistance from repeated exposure to L3 over time, high worm burdens are most likely to occur in dogs that have not been exposed previously to any mosquitoes with L3 and are then bitten by many mosquitoes over a 3-mo period.
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Clinical Findings: The clinical signs of heartworm disease depend on the stage of the life cycle, the severity of infection, and the host response to infection. The animal may begin to cough 2-3 mo before microfilariae are produced and antigen begins to circulate. Ascites may develop in right-sided heart failure from cor pulmonale or from mechanical dysfunction of the tricuspid valve as in postcaval syndromes. In ~10% of dogs with heartworms, an intense immune reaction by the host clears the microfilariae; severe pulmonary reactions are seen, and coughing is the primary clinical sign. Clinical signs in cats are primarily intermittent respiratory disease (coughing or dyspnea) or sporadic vomiting not associated with eating. The respiratory signs mimic those of bronchial asthma and initially respond to corticosteroid administration. Cats may present with acute dyspnea or collapse with no previous respiratory signs. Initial respiratory signs often occur 4-6 mo after the peak mosquito season. Diagnosis: Diagnostic testing for dirofilariasis includes a complete blood count, Knott's test, thoracic radiographs, fecal examination, ECG, immunofluorescent antibody (microfilariae), ELISA-adult antibody (cats only), ELISA-adult antigen, tracheal wash, and arteriogram. Concentration techniques (modified Knott's and filter tests) successfully demonstrate microfilariae in a blood sample in ~60% of dogs and <10% of cats with heartworms. Because microfilariae survive after adult worms have died, a small percentage of dogs can have microfilaremia but no adults in the heart. Occult infections, in which the animal is amicrofilaremic, can be seen when the infection is due to immature (<6 mo old) worms, a single worm, or worms of all the same sex. Although the glycoprotein detected by most assays is found throughout the parasite, the major source of circulating antigen is the reproductive tract of the mature female heartworm. The maturity and number of females influences the amount of antigen. Animals with immature worms and low worm burdens (especially cats) will be antigen negative—even when worms are present in the pulmonary arteries and clinical signs are present. Thoracic radiographs can be a screening tool for dogs and cats with clinical signs suggestive of heartworm disease. In dogs, the pulmonary arteries can be tortuous and enlarged, with an enlarged pulmonary arterial segment at the 1 o'clock position on a ventrodorsal view. Enlarged caudal pulmonary arteries are the most consistent lesion in cats with heartworms. Echocardiograms are especially useful in diagnosis of postcaval syndromes and ascitic conditions associated with heartworm disease. Treatment in Dogs: Steps to manage treatment of dogs infected with heartworms consist of the following: 1) diagnostic evaluations (before therapy) to determine subclinical disease, especially of the liver and kidneys; 2) adulticidal therapy to eliminate mature worms; 3) a rest period of 4-6 wk to allow the dog to recover from the lung injury associated with worm death; 4) microfilaricidal therapy if required; 5) a test for microfilariae to determine success of microfilaricidal therapy; 6) an antigen test to determine success of adulticidal therapy; and 7) preventive medication. Use of aspirin, aspirin and dipyridamole, serotonin antagonist, short-acting heparin, and high-dose corticosteroids to decrease the clinical significance of heartworm lesions has been unsuccessful. Because of the pressure overload of heartworm disease, treatment with digitoxin is usually not recommended. An angiotensin-converting enzyme inhibitor may be used in severe right ventricle hypertrophy. The interstitial edema associated with acute signs of worm death is not aided by diuretic therapy. Adulticidal therapy eliminates the adult heartworms and allows repair of damage where fibrosis has not occurred. Death of the worms (either spontaneous or induced) in both dogs and cats is associated with severe parenchymal lung damage, and limitation of exercise is critical after adulticidal therapy. Thiacetarsamide (2.2 mg/kg, four IV doses over 2 days) will kill most male and some female worms but has poor efficacy against immature and young female worms. Dogs should be rested for 4-6 wk. Complications of worm death often include impaired pulmonary function and vessel damage, which may initiate disseminated intravascular coagulation (DIC). Dyspnea after adulticidal therapy is an emergency. Nasal oxygen and an immediate-acting glucocorticoid at doses used in shock are needed to provide adequate oxygenation and decrease the acute lung injury. Many dogs will respond within 24 hr. Because of the fragile nature of the capillary beds of the lungs, no exercise or stress should be allowed during this time. Ivermectin at 50 µg/kg or milbemycin at the preventive dose is effective within 2-3 wk. Most microfilariae are killed quickly, and reactions, which usually occur within 1 hr of administration, are associated with high microfilariae counts in small dogs. Concentration techniques should be used to assess microfilarial status. Antigen assays 12-16 wk after successful adulticidal therapy should be negative.
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Treatment in Cats: After the diagnosis has been confirmed, the therapeutic options must be carefully considered. Because feline heartworm disease can result in no signs or signs such as chronic vomiting or intermittent respiratory signs, owners often think the disease is less severe than it is. Without treatment, acute complications and death occur in a small percentage of cats. In addition, the life span of the adult heartworm is shorter in cats than in dogs, and spontaneous recovery is possible. Treatment of feline heartworm disease with thiacetarsamide sodium (2.2 mg/kg, given slowly IV, b.i.d., for 2 days) is tolerated by cats without immediate complications of hepatotoxicity or renal toxicity. In symptomatic cats, clinical signs tend to improve after therapy. Complications after therapy are more severe in cats than in dogs and are usually related to embolization. Sudden death from embolization can occur, especially within the first 10 days after adulticidal therapy. Embolization can result in severe lung infarction, hemoptysis, and dyspnea. There is evidence that aspirin may inhibit prostaglandin formation and thus increase leukotriene production in the lungs; the result would be bronchospasm and pulmonary hypertension. Aspirin is not currently recommended for use in feline heartworm disease, and it may be contraindicated when acute embolization occurs. If a cat was antigen positive before therapy, the antigen test should be negative 12 wk after adulticide therapy; a positive test would indicate that adult heartworms are still present. The onset of acute respiratory signs in a cat with heartworm disease is an emergency, and immediate treatment is needed. The radiographic signs of severe lung pathology should not be interpreted as consolidation or pneumonia. Prevention: In dogs, diethylcarbamazine (DEC), ivermectin, and milbemycin oxime are orally administered preventives. Dogs >6 mo old should test negative for microfilariae and antigen assay before preventive medications are administered. Dogs <6 mo old can be started on preventive medication but should be tested for microfilariae and antigen 6 mo to1 yr later. DEC is administered daily from 1 mo before to 2 mo after the mosquito season. Ivermectin and milbemycin oxime are administered once monthly from 1 mo after the onset to 1 mo after the end of the mosquito season.

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Digestive System Pathophysiology: The major mechanisms of diarrhea are increased permeability, hypersecretion, and osmosis. Disorders of motility are often secondary. In healthy animals, water and electrolytes continuously transfer across the intestinal mucosa. Secretions (from blood to gut) and absorptions (from gut to blood) occur simultaneously. In clinically normal animals, absorption exceeds secretion, ie, there is net absorption. Inflammation in the intestines can be accompanied by an increase in “pore size” in the mucosa, permitting increased flow through the membrane (“leak”) down the pressure gradient from blood to the intestinal lumen. If the amount exuded exceeds the absorptive capacity of the intestines, diarrhea results. The size of the material that leaks through the mucosa varies, depending on the magnitude of the increase in pore size. Large increases in pore size permit exudation of plasma protein, resulting in protein-losing enteropathies (eg, lymphangiectasia in dogs, paratuberculosis in cattle, nematode infections). Greater increases in pore size result in the loss of red blood cells, producing hemorrhagic diarrhea (eg, hemorrhagic gastroenteritis, parvovirus infection, severe hookworm infection). Hypersecretion is a net intestinal loss of fluid and electrolytes, which occurs independent of changes in permeability, absorptive capacity, or exogenously generated osmotic gradients. Enterotoxic colibacillosis is an example of diarrheal disease due to intestinal hypersecretion; enterotoxigenic Escherichia coli produce enterotoxin that stimulates the crypt epithelium to secrete fluid beyond the absorptive capacity of the intestines. The villi, along with their digestive and absorptive capabilities, remain intact. The fluid secreted is isotonic, alkaline, and free of exudates. The intact villi are beneficial because a fluid (administered PO) that contains glucose, amino acids, and sodium is absorbed, even in the face of hypersecretion. Osmotic diarrhea occurs when inadequate absorption results in a collection of solutes in the gut lumen, which cause water to be retained by their osmotic activity. It occurs in any condition that results in nutrient malabsorption or maldigestion. Malabsorption is failure of digestion and absorption due to some defect in the villous digestive and absorptive cells, which are mature cells that cover the villi. Several epitheliotropic viruses directly infect and destroy the villous absorptive epithelial cells or their precursors, eg, coronavirus, transmissible gastroenteritis virus of piglets, and rotavirus of calves. Feline panleukopenia virus and canine parvovirus destroy the crypt epithelium, which results in failure of renewal of villous absorptive cells and collapse of the villi; regeneration is a longer process after parvoviral infection than after viral infections of villous tip epithelium (eg, coronavirus, rotavirus). Intestinal malabsorption also may be caused by any defect that impairs absorptive capacity, such as diffuse inflammatory disorders (eg, lymphocytic-plasmacytic enteritis, eosinophilic enteritis) or neoplasia (eg, lymphosarcoma). Other examples of malabsorption include defects of pancreatic secretion that result in maldigestion. Rarely, because of failure to digest lactose (which, in large amounts, has a hyperosmotic effect), neonatal farm animals or pups may have diarrhea while they are being fed milk. Clinical Findings of Gastrointestinal Disease: Blood and fibrinous casts in the feces indicate a hemorrhagic, fibrinonecrotic enteritis of the small or large intestine, eg, bovine viral diarrhea, coccidiosis, salmonellosis, or swine dysentery. Black, tarry feces (melena) indicate hemorrhage in the stomach or upper part of the small intestine. Tenesmus of GI origin usually is associated with inflammatory disease of the rectum and anus. Small amounts of soft feces may indicate a partial obstruction of the intestines. Abdominal distention can result from accumulation of gas, fluid, or ingesta, usually due to hypomotility (functional obstruction, adynamic paralytic ileus) or to a physical obstruction (eg, foreign body or intussusception). Distention may, of course, result from something as direct as overeating. A “ping” heard during auscultation and percussion of the abdomen indicates a gas-filled viscus. A sudden onset of severe abdominal distention in the adult ruminant usually is due to ruminal tympany. Varying degrees of dehydration and acid-base and electrolyte imbalance, which may lead to shock, occur when large quantities of fluid are lost (eg, in diarrhea or sequestered in intestinal obstruction) or in gastric or abomasal volvulus. Abdominal pain is due to stretching or inflammation of the serosal surfaces of abdominal viscera or the peritoneum; it may be acute or subacute, and its manifestation varies among species. In horses, acute abdominal pain is common (see colic, Colic In Horses: Introduction). Subacute pain is more common in cattle and is characterized by reluctance to move and by grunting with each respiration or deep palpation of the abdomen. Abdominal pain in dogs and cats may be acute or subacute and is characterized by whining, meowing, and abnormal postures (eg, outstretched forelimbs, the sternum on the floor, and the hindlimbs raised). Examination of the Gastrointestinal Tract: Sudan III stain is a sensitive test for steatorrhea in small animals. Cytology of a rectal or colonic mucosal smear stained with new methylene blue or Wright's stain for fecal leukocytes is useful to detect inflammatory bowel disease. Principles of Therapy

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Slowing intestinal transit may be counterproductive to the defense mechanism of diarrhea, which acts to evacuate harmful organisms and their toxins. In general, anticholinergic drugs probably are justified only for short-term symptomatic relief of pain and tenesmus associated with inflammatory diseases of the colon and rectum. In some disorders of gastric or colonic motility, prokinetic drugs (metoclopramide, cisapride) may be useful. Campylobacteriosis: Introduction Campylobacteriosis, caused by Campylobacter jejuni or C coli Etiology: Campylobacter is a gram-negative, microaerophilic, slender, curved, motile bacterium with a polar flagellum. Campylobacter (Vibrio) sp was once associated with swine dysentery, but this is now recognized as being caused by Treponema hyodysenteriae . Because of the slow growth and microaerophilic requirements of Campylobacter , standard culture methods require selective media that incorporate various antibiotics to suppress competing fecal microflora. Transmission and Epidemiology: As with most intestinal pathogens, fecal-oral spread and food- or water-borne transmission appear to be the principal avenues for infection. Clinical Findings: The diarrhea appears to be most severe in young animals. Typical signs in dogs include mucus-laden, watery, and/or bile-streaked diarrhea (with or without blood) that lasts 3-7 days; reduced appetite; and occasional vomiting. Fever and leukocytosis may also be present. In certain cases, intermittent diarrhea may persist >2 wk; in some, it may be present for months. Lesions: Congested and edematous colons were found in dogs 43 hr after inoculation; microscopically, there was reduction in epithelial height, loss of brush border, and reduced numbers of goblet cells in the colon and cecum. Hyperplastic epithelial glands resulted in a thickened mucosa. Histologic changes in calves primarily involve the jejunum but also can involve the ileum and colon. The lesions can vary from mild changes to severe hemorrhagic enteritis. The mesenteric lymph nodes are edematous. Diagnosis: The standard method for diagnosis is microaerophilic culture of feces at 42°C; a special medium is commercially available. Treatment and Control: Erythromycin, the drug of choice for Campylobacter diarrhea in man, is also effective in other animals. Gentamicin, furazolidone, doxycycline, and chloramphenicol also can be used. Some animals continue to shed the organism despite antibiotic therapy. Salmonellosis: Introduction Salmonellosis is caused by many species of salmonellae and characterized clinically by one or more of three major syndromes—septicemia, acute enteritis, and chronic enteritis. Young calves, piglets, lambs, and foals usually develop the septicemic form (see diarrhea in neonatal ruminants, and diarrheal diseases of foals. Adult cattle, sheep, and horses commonly develop acute enteritis, and chronic enteritis may develop in growing pigs and occasionally in cattle (see also the chapters on intestinal diseases in each of the major domestic species, et seq. Pregnant animals may abort. Salmonellosis occurs infrequently in dogs and cats and is characterized by acute diarrhea with or without septicemia. Transmission to man occurs via contaminated drinking water, milk, meat, and foods such as cake mixes that use contaminated ingredients; poultry and eggs are particularly important sources of infection. Etiology, Epidemiology, and Pathogenesis: Feces of infected animals can contaminate feed and water, milk, fresh and processed meats from abattoirs, plant and animal products used as fertilizers or feedstuffs, pasture and rangeland, and many inert materials. The organisms may survive for months in wet, warm areas such as in feeder pig barns or in water dugouts but survive <1 wk in composted cattle manure. The usual route of infection is oral and, after infection, the organism multiplies in the intestine and causes enteritis. Greater susceptibility of the young may be due to high gastric pH, absence of a stable intestinal flora, and limited immunity. Penetration of bacteria into the lamina propria and production of cytotoxin and enterotoxin likely contribute to gut damage and diarrhea. There is a marked inflammatory response, and salmonellae are engulfed by phagocytic cells; however, the bacteria can survive and multiply in these cells. Septicemia may follow with subsequent localization in brain and meninges, pregnant uterus, distal aspects of the limbs, and tips of the ears and tails, which can result, respectively, in meningoencephalitis, abortion, osteitis, and dry gangrene of the feet, tail, or ears. Infection may persist in lymph nodes or tonsils, with no salmonellae in the feces. Latent carriers may begin shedding the organism or even develop clinical disease under stress.
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Cattle and Sheep: In calves and lambs, the disease is usually endemic on a particular farm, with sporadic explosive outbreaks. Subclinical infection with occasional herd outbreaks may occur in adult cattle. Horses: Mares may be inapparent shedders and, despite several negative cultures before foaling, may shed the bacteria at parturition and infect the newborn foal. Dogs and Cats: Many dogs and cats are asymptomatic carriers of salmonellae. Clinical Findings: Septicemia is the usual syndrome in newborn calves, lambs, foals, and piglets, and outbreaks may occur in pigs up to 6 mo old. Illness is acute, depression is marked, fever (105-107°F [40.5-41.5°C]) is usual, and death occurs in 24-48 hr. In pigs, a dark red to purple discoloration of the skin is common, especially at the ears and ventral abdomen. Nervous signs may occur in calves and pigs; these animals may also suffer from pneumonia. Mortality may reach 100%. Acute enteritis is the common form in adults as well as in calves, usually ≥1 wk old. Initially, there is fever (105107°F [40.5-41.5°C]), followed by severe watery diarrhea, sometimes dysentery, and often tenesmus. In a herd outbreak, several hours may lapse before the onset of diarrhea, at which time the fever may disappear. The feces, which vary considerably, may have a putrid odor and contain mucus, fibrinous casts, shreds of mucous membrane, and in some cases, large blood clots. Rectal examination causes severe discomfort, tenesmus, and commonly dysentery. A marked leukopenia and neutropenia are characteristic of the acute disease in horses. Conjunctivitis is sometimes seen in affected cats. Subacute enteritis may occur in adult horses and sheep on farms where the disease is endemic. The signs include mild fever (103-104°F [39-40°C]), soft feces, inappetence, and some dehydration. In cattle, the first signs may be fever and abortion, followed several days later by diarrhea. Chronic enteritis is a common form in pigs and adult cattle. There is persistent diarrhea, severe emaciation, intermittent fever, and poor response to treatment. The feces are scant and may be normal or contain mucus, casts, or blood. In growing pigs, rectal stricture may be a sequela if the terminal part of the rectum is involved. Affected pigs are anorectic and lose weight; the abdomen becomes grossly distended. Diagnosis: This depends on the clinical signs and on the laboratory examination of feces, tissues from affected animals, feed (including all mineral supplements used), water supplies, and feces from wild rodents and birds that may inhabit the premises. The clinical syndromes usually are characteristic but must be differentiated from several similar diseases in each species as follows: Cattle—diarrhea due to enterotoxigenic Escherichia coli , dysentery due to verotoxigenic E coli , coccidiosis, cryptosporidiosis, the alimentary tract form of infectious bovine rhinotracheitis, bovine viral diarrhea, hemorrhagic enteritis due to Clostridium perfringens types B and C, arsenic poisoning, secondary copper deficiency (molybdenosis), winter dysentery, paratuberculosis, ostertagiasis, and dietetic diarrhea. Sheep—enteric colibacillosis, septicemia due to Haemophilus sp or pasteurellae, and coccidiosis. Pigs—enteric colibacillosis of newborn pigs and weanlings, swine dysentery, campylobacteriosis, and the septicemias of growing pigs (which include erysipelas, hog cholera, and pasteurellosis). Horses—septicemia (due to Escherichia coli , Actinobacillus equuli , or streptococci) and colitis-X. The lesions are those of a septicemia or a necrotizing fibrinous enteritis, or both. Lesions are most severe in the lower ileum and the large intestine and vary from shortening of villi with loss of the epithelium to complete loss of intestinal architecture. There is a neutrophilic reaction in the lamina propria, and thrombi may be seen in blood vessels in this region. Treatment: Early treatment is essential for septicemic salmonellosis, but there is controversy regarding the use of antimicrobial agents for intestinal salmonellosis. Oral antibiotics may deleteriously alter the intestinal microflora, interfere with competitive antagonism, and prolong shedding of the organism. There is also concern that antibiotic-resistant strains of salmonellae selected by oral antibiotics may subsequently infect man. Broad-spectrum antibiotics are used parenterally to treat the septicemia. Trimethoprim-sulfonamide combinations are often effective. Alternatives are ampicillin, fluoroquinolones, or third-generation cephalosporins. Oral medication should be given in drinking water because affected animals are thirsty due to dehydration, and their appetite is generally poor. Fluid therapy to correct acid-base imbalance and dehydration is necessary. Calves, adult cattle, and horses need large quantities of fluids. Antibiotics such as ampicillin or cephalosporins lead to lysis of the bacteria with release of endotoxin. Nonsteroidal anti-inflammatory drugs may be used to reduce the effects of endotoxemia. Horses with acute intestinal salmonellosis are severely acidotic and hyponatremic and may need to be treated initially with 5% sodium bicarbonate, IV, at 6-9 qt/1000 lb (5-8 L/450 kg) body wt. This is followed by balanced electrolytes containing potassium to correct the hypokalemia that may follow correction of the acidosis. In horses, flunixin meglumine is recommended for its antiendotoxic properties. Corticosteroids are not recommended because of their immunosuppressive effects and their potential to exacerbate laminitis. Prevention of Introduction:
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Every effort must be made to prevent introduction of a carrier; animals should be purchased directly only from farms known to be free of the disease and should be isolated for ≥1 wk while their health status is monitored. Hernias Hernias involving the abdomen occur when abdominal contents protrude through a natural or abnormal opening in the body wall. They may be congenital or acquired. In acquired hernias, there is usually a history of trauma. Congenital hernias may involve the diaphragm or the abdominal wall. Hernias involving the diaphragm are of three main types: peritoneopericardial, in which abdominal contents are found extending into the pericardial sac; pleuroperitoneal, in which abdominal contents are found within the pleural cavity; and hiatal, in which the abdominal esophagus, gastroesophageal junction, and/or portions of the stomach protrude through the esophageal hiatus of the diaphragm into the thoracic cavity. Clinical signs vary from asymptomatic to severe and depend on the amount of herniated tissue and its effect on the organ it is displacing. Hiatal hernias may be “sliding” and result in clinical signs of reflux esophagitis (anorexia, salivation, and/or vomition) that may be intermittent. Diagnosis is through radiology: contrast studies are often needed for confirmation. Fluoroscopy or endoscopy is useful in the diagnosis of sliding hiatal hernias. Correction of the aforementioned hernias is best accomplished through surgery. In the case of hiatal hernias, medical therapy, including the use of systemic antacid preparations and dietary modification, may control signs if mild. Hernias involving the abdominal wall include umbilical, inguinal, or scrotal. Umbilical hernias are secondary to failure of the normal closure of the umbilical ring and result in protrusion of abdominal contents into the overlying subcutis. Size varies depending on the extent of the umbilical defect and the amount of abdominal contents contained. The etiology in both large and small animals is likely to have a genetic component; however, excess traction on an oversized fetus or cutting the umbilical cord too close to the abdominal wall are other possible causes. Diagnosis is usually straightforward, especially if the hernia is manually reducible. If irreducible, it must be differentiated from an umbilical abscess, which is common in large animals. Umbilical hernia and umbilical abscess often occur together, especially in cattle and swine. Exploratory puncture may be required for confirmation. Correction is surgical. Inguinal hernias in the male pig are common and they usually extend into the scrotum. Shaking the suspended piglet by the forelegs causes even a small hernial bulge to become visible. In female pigs, this defect is invariably accompanied by arrested genital development; such animals are sterile, and surgery is indicated only when the size of the process is a threat to the growth of the pig to market weight. Inguinal hernias in male foals often resolve spontaneously during the first year of life. For this reason, early corrective surgery is not indicated unless the hernia is strangulated or of such a magnitude that it interferes with gait. Strangulated inguinal hernia in stallions is fairly frequent and is characterized by signs of constant and severe abdominal pain. It is readily recognized by rectal palpation and may be reduced, under general anesthesia, by rectal manipulation. If this fails, immediate surgery is necessary. Inguinal hernias in cattle are rare although sometimes seen in males. Esophagus Clinically significant esophageal disorders generally manifest themselves as swallowing dysfunction and regurgitation, especially evident with the introduction of solid food. These disorders, found predominantly in small animals, can be classified as congenital megaesophagus, vascular ring entrapment anomalies, and achalasia. Congenital megaesopahagus is thought to result from developmental anomalies in esophageal neuromuscular innervation. Vascular ring entrapment anomalies most commonly result from persistence of the right fourth aortic arch during embryonic development, which results in esophageal entrapment at the heart base by the right fourth aortic arch, left atrium, pulmonic artery, and the ligamentum arteriosum. This obstructs food passage and results in food retention and subsequent esophageal dilation anterior to the anomaly. Boston Terriers, German Shepherd Dogs, and Irish Setters have higher breed incidences. Cricopharyngeal achalasia is a term used to describe a failure, or asynchrony, of the cricopharyngeous muscle to relax during swallowing, thereby preventing the normal passage of a food bolus from the caudal pharynx to the cranial esophagus. It has been mainly identified in toy breeds and rarely in cats. Lower esophageal sphincter achalasia is now considered to be a component of a more generalized esophageal motor disturbance (ie, megaesophagus) and no longer a distinct entity. Definitive diagnosis is usually via contrast radiography or fluoroscopy of the swallowing reflex. Treatment is directed at the primary etiology. Some mildly affected dogs will improve over time; however, those that don't have a poor long-term prognosis, with aspiration pneumonia being a frequent and often lethal complication. Esophageal diverticula may involve the cervical esophagus just cranial to the thoracic inlet or be epiphrenic (just cranial to the diaphragm). Clinical signs depend on severity and are seen in only 10-15% of cases but may include impaction, esophagitis, and rarely rupture or tracheoesophageal fistula formation. Treatment is via surgical removal. Estimation of Age by Examination of the Teeth Horses:

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In horses, the incisor teeth are most often used to estimate age. The deciduous incisors are smaller than the permanent teeth and have a distinct neck. The more useful signs are arranged chronologically in the following list: Birth to 5 yr: 5 yr: I 1 and I 2 level, labial border of I 3 in wear. 6 yr: Cup gone from I 1. 7 yr: All lower incisors level. Cup gone from I 2. Hook in upper I 3. Cement has worn off, changing the color from yellow to bluish white. 8 yr: Dental star appears in I 1. Cup gone from I 3. 9 yr: I 1 round. 10 yr: I 2 round. Distal end of Galvayne's groove emerges from gum on upper I 3. 13 yr: Enamel spots are small and round in lower incisors. Dental stars are in the middle of the table surfaces. 15 yr: Dental stars round, dark, and distinct. Galvayne's groove halfway down. 16 yr: I 1 triangular. 17 yr: I 2 triangular. Enamel spots gone from lower incisors. Cattle: Signs of wear are much less reliable than eruption for estimation of age because wear is largely determined by nutrition, ration, and sand content of soil. Eruption times of the permanent incisors are primarily used to estimate age up to 5 yr. Except for very aged animals, the teeth are rarely used to determine the age of adult cattle. Birth to 5 yr: See Table: Eruption of the Teeth. 5 yr: All incisors in wear. Occlusal surface of I 1 beginning to level, ie, the ridges on the lingual surface are wearing out and the corresponding border of the occlusal surface is becoming a smooth curve instead of a zigzag line. 6 yr: I 1 is leveled and neck is visible. 7 yr: I 2 is leveled and neck is visible. 8 yr: I 3 is leveled and neck is visible. I 4 may be level. 9 yr: C is leveled and neck is visible. As cattle continue to age, the teeth wear shorter and more neck becomes visible; they loosen in the sockets and eventually drop out. Dogs: The following data were found reliable in ~90% of large dogs. There is more variation in small dogs (especially toy breeds) and in dogs with undershot or overshot jaws. Even, or level, bites usually result in excessive wear. 1 ½ yr: Cusps worn off lower I 1. 2 ½ yr: Cusps worn off lower I 2. 3 ½ yr: Cusps worn off upper I 1. 4 ½ yr: Cusps worn off upper I 2. 5 yr: Cusps of lower I 3 slightly worn. Occlusal surface of lower I 1 and I 2 rectangular. Slight wear of canines. 6 yr: Cusps worn off lower I 3. Canines worn blunt. Lower canine shows impression of upper I 3. 7 yr: Occlusal surface of lower I 1 elliptical with the long axis sagittal. 8 yr: Occlusal surface of lower I 1 inclined forward. 10 yr: Lower I 2 and upper I 1 have elliptical occlusal surfaces. 12 yr: Incisors begin to fall out (unless care has been taken to maintain healthy gingival and periodontal tissues). Large Animals: Overview In the swine industry, removal or amputation of deciduous canine teeth in piglets and tusk amputation in breeding boars may be part of routine management. Signs of Dental Disease: The classic signs of dental disease in horses include difficulty or slowness in feeding and a reluctance to drink cold water. During the chewing process, the horse may stop for a few moments and then start again. Sometimes, the head is held to one side as if the horse were in pain. Occasionally, the horse may quid, ie, it may pick up its food, form it into a bolus but drop the bolus from the mouth after it has been partially chewed. Occasionally, the semichewed mass of feed may become packed between the teeth and the cheek. To avoid using a painful tooth or a sore mouth, the horse may bolt its food and subsequently may suffer indigestion or colic. Uncrushed, unmasticated grain may be noticed in the feces. Other signs of dental disease in horses include excessive salivation and blood-tinged mucus in the mouth, accompanied by the fetid breath of dental decay. There may be a lack of desire to eat hard grain accompanied by loss of body condition or poor coat condition. Extensive dental decay and accompanying periostitis and root abscessation may lead to empyema of the paranasal sinuses and intermittent unilateral nasal discharge. There may be facial or mandibular swelling and development of mandibular fistulas from apical infections of the lower cheek teeth.

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Horses may be reluctant to take the bit, shake their head when being ridden, or resist training techniques due to irregularly worn cheek teeth and sharp edges on the maxillary cheek teeth and accompanying buccal mucosa laceration. The presence of “wolf” teeth in horses may or may not be associated with resistance to the bit. Irregular Wear Except for pigs, most large animals have an intermandibular space that is narrower than the intermaxillary space; that is, they are anisognathic. Periodontal Disease In all animals, a degree of inflammatory change occurs during the eruption of both the deciduous and permanent teeth. However, if malocclusion occurs, severe periodontal disease is inevitable. In horses, this is a common sequela of oral trauma, dental fractures, impactions, and most importantly irregular wear. Dental Decay Infection may be introduced into the pulp chamber of the teeth by various routes, eg, after amputation of teeth (in pigs or in new world camelids). In horses, hypoplasia of the enamel of the upper cheek teeth may predispose to caries of cementum and subsequent pulpitis and apical osteitis. Depending on the site of the tooth that is decayed, there may be accompanying signs of maxillary sinusitis, local cellulitis, periostitis, alveolar periodontitis, and fistula formation. When dental decay is advanced, extraction of the affected tooth is recommended. Small animal Dentistry Periodontal Disease This bacterial infection of the tissue surrounding the teeth causes inflammation of the gingivae, periodontal ligament, cementum, and alveolar bone. Ultimately, teeth are lost due to the loss of their supporting tissues. This is the major reason for tooth loss in dogs. Etiology and Pathogenesis: Periodontal disease is caused by gross accumulation of many different bacteria at the gingival margin due in part to a lack of proper oral hygiene. Over a period of weeks, the flora changes from nonmotile, gram-positive, coccoid, aerobic bacteria to more motile, gram-negative, rod-shaped, anaerobic bacteria. As the local bacterial flora increases in mass to 10-20 times normal, gingivitis occurs. The accumulation of bacterial metabolic products increases epithelial permeability in crevicular epithelial desmosomes and allows antigens to contact connective tissue. Metabolic products of bacterial metabolism include hydrogen sulfide, ammonia, endotoxin, hyaluronidase, chondroitin sulfatase, mucopeptides, lipoteichoic acids, acetate, butyrate, isovalerate, and propionate. These bacterial products and host defense mechanisms cause tissue necrosis. Polymorphonuclear leukocytes (PMN) migrate through the sulcular epithelium and form a barrier between the subgingival bacteria and the gingiva. With overwhelming bacterial challenge, PMN die in increasing numbers and release breakdown products. The immune system produces lymphokines that participate in tissue destruction, which follows the path of the local vascular supply. Accelerated tissue destruction and inappropriate repair cause loss of periodontal support. Two forms of disease are recognized: gingivitis and periodontitis. In gingivitis, the inflammation of the marginal gingival tissues is induced by bacterial plaque and does not affect the periodontal ligament or alveolar bone. There is a change from coral-pink to red or purple, swelling of the gingival margin, and a serous or purulent exudate in the sulcus. The gingivae tend to bleed on contact. Fetid breath is common. Gingivitis is reversible with proper tooth cleaning but, if untreated, may lead to periodontitis. In periodontitis, the destructive inflammatory process of the periodontium is induced and driven by bacterial plaque that contains specific bacteria that destroy the gingiva, periodontal ligament, alveolar bone, and root cementum. It usually occurs after years of plaque, calculus, and gingivitis. It is irreversible and results in permanent loss of tooth support. There is apical migration of the epithelial attachment and resorption of supporting alveolar bone. Affected teeth may show increased mobility, concurrent gingivitis, and subgingival calculus. Dogs on a hard diet develop fewer problems due to the mechanical cleaning effect of the food. Caudal teeth have more problems than rostral teeth. The maxilla is affected more severely than the mandible, and buccal surfaces have more disease than lingual surfaces. Gingivitis often becomes severe at ~2 yr of age but resolves if treated. Periodontitis usually begins at 4-6 yr of age and, if untreated, progresses to tooth loss. Treatment: The basic principle is that active periodontal disease will not develop around a clean tooth. Gingivitis usually can be treated by thorough cleaning of the teeth, including below the gingival margin.
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Periodontitis needs to be treated with thorough cleaning above and below the gum line. In areas of increased subgingival depth (>4 mm), surgical means (usually gingivectomy) should be used to gain access to the root surface for cleaning. Teeth can generally be salvaged until they have lost 75% of their bone support from one or more roots. This can be evaluated by radiography of the jaws, which should be performed if periodontal disease is advanced. Infrabony defects (defects below the crest of the alveolar bone) require flap surgery. Defects on the palatal surface of maxillary canine teeth, which are infrabony in character and invade or approximate the nasal cavity, should be treated with infrabony grafting procedures before a decision is made to extract the tooth. Extraction of such teeth frequently leaves oronasal fistulas, which require surgical repair. Gingival Hyperplasia (Fibromatosis gingivae, Fibromatous epulis, Epulis) This benign overgrowth of the epithelial and connective tissue of the gums usually originates near the gingival margin. The tissue is relatively insensitive and tough and has the density of fibrous connective tissue. The growths usually have a broad base of attachment, are the color of the normal gum or more pale, and may grow large enough to completely cover the surfaces of several teeth. Predisposition may exist among brachycephalic breeds, in which the condition is termed familial gingival hypertrophy. Epulis sometimes refers to giant-cell epulis or tumor of the gum of dogs. This tumor usually is localized to a single tooth. Biopsy is encouraged to assure proper diagnosis, treatment, and prognosis. Gingival hyperplasia is most common in older dogs and is usually asymptomatic. Hair, food, and debris may collect between the growth and the teeth and cause irritation and halitosis. Gingivectomy by electrosurgical techniques is the most satisfactory treatment. Endodontic Disease Pulpal Hyperemia: The pulp may become acutely inflamed due to trauma or extension of lesions adjacent to the pulp (eg, caries and resorption). Because the pulp is totally confined in dentin, inflammatory swelling may result in pressure necrosis if the insult is prolonged. Severity of the reaction appears to be directly proportional to the extent of injury. Therefore, small injuries that produce transient hyperemia of the pulp may resolve, and a healthy pulp may be reestablished. Steroid therapy is indicated immediately after trauma. Cleaning out carious lesions and placing zinc oxide eugenol into resorptions and former carious areas may allow local anesthesia and resolution of hyperemia. Pulpitis: Inflammation of the pulp with pressure necrosis and abscessation is irreversible. In general, the abscess cavity is initially sterile unless the tooth has been opened to the oral environment by trauma, resorption, or caries. Teeth with pulpitis often are acutely painful, and the animal resents manipulation or percussion of the tooth. As the pulp dies and gas pressure increases in the pulp cavity, blood is forced into the dentinal tubules and the teeth often change to a reddish brown or dark gray color. Periapical Lesions: A periapical abscess is a cavitational lesion at the end of the root due to pulpal disease. These areas generally can be seen on radiographs as radiolucent circular areas around the end of the root. Such abscesses can sometimes be palpated over the bony prominence of root ends. Abscesses may extend by pressure drainage into adjacent bone and soft-tissue areas and exit extraorally into the soft-tissue space between the jaws, beneath the eye, or into the buccal vestibule. Treatment is endodontic therapy (root canal) on the associated tooth, and the abscess and associated fistula usually resolve within a few weeks. When endodontic therapy cannot be done, the tooth should be extracted. Dental Caries Dental decay is uncommon in dogs and cats, possibly because of differences in oral flora, diets largely free of readily fermentable carbohydrates, and the slightly alkaline pH of canine saliva. In dogs, decay usually is seen as pits on the flat surfaces or on the necks of the molar teeth. “Neck” Lesions in Cats In domestic cats, a destructive disease involving tooth crown and roots is commonly called “neck” lesions. Three variations of this disease have been recognized: cervical line erosions, external odontoclastic resorption, and internal odontoclastic resorption.

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Cervical line erosions are characterized by a superficial loss of enamel from the crown of the tooth with clean dentin margins. The cause of cervical line erosions is unknown but may have dietary implications. This group represents ~10% of the neck lesions in the feline population. External odontoclastic resorption represents ~70% of the neck lesions in cats. It is characterized by the presence of osteoclasts, odontoclasts, and osteoblasts in the lesion. While restorative techniques are moderately successful in early lesions, most restoration attempts are futile, and extraction is the treatment of choice. Internal odontoclastic resorption starts as a destructive process in the odontoblast layer inside the tooth and extends into the dentin. Vasodentin, found in the dentinal layer of feline teeth, may also act as a site for resorption to start. Ultimately, tooth perforation occurs. Treatment in the early stage includes root canal treatment when feasible. In all three forms of “neck” lesions, dental radiography is essential to determine whether treatment is feasible. Feline Stomatitis Complex The oral cavity of the domestic cat may react intensely to disease and result in painful, severe inflammation of the oral cavity. Soft-tissue biopsy includes heavy infiltration of plasma cells and lymphocytes. “Plasmacyticlymphocytic stomatitis” is a sign of one or more severe diseases in the cat and must be diagnosed accurately to ensure successful treatment. Causes of plasmacytic-lymphocytic stomatitis include retrovirus infection (feline leukemia, feline immunodeficiency virus), calicivirus infection (especially in cats with chronic faucitis), concurrent odontoclastic resorption (“neck” lesions), polyclonal gammopathy (hypergammaglobulinemia), concurrent diabetes mellitus, chronic interstitial nephritis, or other debilitating diseases and malnutrition. Initial treatment includes controlling or eliminating the cause and aggressive dental prophylaxis with mandatory home care. Unfortunately, many cats have advanced disease and are far too painful to allow home care. The treatment of choice is full mouth extractions, although fortunately, the canine teeth can usually be salvaged. Steroid therapy is only palliative and is best used only on a short-term basis after surgical intervention. Surgical pain is controlled with mandibular and maxillary nerve blocks followed by butorphenol PO for 3 days. Antibiotic therapy controls any chance of septicemia. Developmental Abnormalities Malocclusion: Malposition of the teeth within the jaw can result in a poor bite. Frequently, it occurs when deciduous teeth are retained and the permanent teeth erupt adjacent to, rather than directly under, them; the roots of the deciduous teeth are not resorbed, and they tilt the erupting permanent teeth into an abnormal position. Other types of dental malocclusion relate to improper relationships between the size of the teeth and that of the jaws. For example, a jaw may be too small for the size of the teeth developing within it, which causes crowding and subsequent malocclusion. Malocclusion may be treated to obtain a functional bite by early extraction of retained deciduous teeth, selective extraction of permanent teeth, or orthodontics. Skeletal malocclusions result from an abnormal relationship of the upper and lower jaws to each other, although the teeth may be properly aligned within the jaw. Treatment is much more difficult and should attempt to achieve a functional bite rather than perfect occlusion. Selective extractions, orthodontics, and in severe cases, orthognathic surgery may be necessary. Enamel Hypoplasia and Dysplasia: During the development of enamel (both deciduous and permanent teeth), fevers and deposition of chemicals within the tooth may cause permanent damage. The canine distemper virus is especially damaging in that it attacks the ameleoblasts (enamel-producing cells) and causes a systemic fever. This results in generalized full-thickness loss of enamel, or enamel hypoplasia. Treatment of enamel hypoplasia includes composite bonding and frequent dental prophylaxis. Treatment of enamel dysplasia includes aggressive polishing of the remaining enamel and possible composite bonding. Maxillofacial Trauma Fractured teeth should be inspected for damage to the pulp. If fractures extend into the pulp, endodontic therapy is required, or extraction must be performed. Lengthwise fractures that extend below the gingival margin can be difficult to repair; if substantial tooth has been lost, what remains should probably be extracted. Fragmented teeth, especially those with multiple roots, often are left to “see what happens”; extraction is usually better due to poor general healing. within a few hours. Thick tissue that has become avascular due to trauma should be removed. Bone fractures require stabilization. Acrylic splints, arch bars, interdental wiring, and cerclage wires can be used. Coccidiosis: Introduction Coccidiosis is a usually acute invasion and destruction of intestinal mucosa by protozoa of the genera Eimeria or Isospora . Infection is characterized by diarrhea, fever, inappetence, weight loss, emaciation, and sometimes death. Coccidiosis is a serious disease in cattle, sheep, goats, pigs, poultry, and also rabbits, in which the liver as well as the

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intestine can be affected. In dogs, cats, and horses, it is less often diagnosed but can result in clinical illness. Other species, of both hosts and protozoa, can be involved, sarcocystosis, and toxoplasmosis. In coccidiasis, animals are infected with coccidia but do not have clinical signs. Coccidiasis is much more prevalent than coccidiosis and is thought to result in poor feed efficiency under intensive rearing conditions. Etiology and Epidemiology: Eimeria and Isospora typically require only one host in which to complete their life cycles. Oocysts enter the environment in the feces of an infected host, but oocysts of Eimeria and Isospora are unsporulated and therefore not infective. Under favorable conditions of oxygen, humidity, and temperature, oocysts sporulate and become infective in several days. During sporulation, the amorphous protoplasm develops into small bodies (sporozoites) within secondary cysts (sporocysts) in the oocyst. In Eimeria spp , the sporulated oocyst has four sporocysts, each containing two sporozoites; in Isospora spp , the sporulated oocyst has two sporocysts, each containing four sporozoites. When the sporulated oocyst is ingested by a susceptible animal, the sporozoites escape from the oocyst, invade the intestinal mucosa or epithelial cells in other locations, and develop intracellularly into multinucleate schizonts (also called meronts). Each nucleus develops into an infective body called a merozoite; merozoites enter new cells and repeat the process. After a variable number of asexual generations, merozoites develop into either macrogametocytes (females) or microgametocytes (males). These produce a single macrogamete or a number of microgametes in a host cell. After being fertilized by a microgamete, the macrogamete develops into an oocyst. The oocysts have resistant walls and are discharged unsporulated in the feces. Oocysts do not survive well at temperatures below -30°C or above 40°C; within this range, they may survive up to 1 yr or more. Coccidia are opportunistic pathogens. If pathogenic, their virulence may be influenced by various stressors. Therefore, clinical coccidiosis is most prevalent under conditions of poor nutrition, poor sanitation, or overcrowding, or after the stresses of weaning, shipping, sudden changes of feed, or severe weather. Of the numerous species of Eimeria or Isospora that can infect a particular host, not all are pathogenic. Most animals acquire Eimeria or Isospora infections of varying degrees when between 1 mo and 1 yr old. Older animals usually are resistant to clinical disease but may have sporadic inapparent infections. Such clinically healthy, mature animals usually can be sources of infection to young, susceptible animals. Clinical Findings: Clinical signs of coccidiosis are due to destruction of the intestinal epithelium and, frequently, the underlying connective tissue of the mucosa. This may be accompanied by hemorrhage into the lumen of the intestine, catarrhal inflammation, and diarrhea. Signs may include discharge of blood or tissue, tenesmus, and dehydration. Diagnosis: Oocysts can be identified in feces by salt or sugar flotation methods. Finding appreciable numbers of oocysts of pathogenic species in the feces is diagnostic, but because diarrhea may precede the heavy output of oocysts by 1-2 days and may continue after the oocyst discharge has returned to low levels, it is not always possible to find oocysts in a single fecal sample; multiple examinations may be required. Treatment: The life cycles of Eimeria and Isospora are considered self-limiting and end spontaneously within a few weeks unless reinfection occurs. Sick animals should be isolated and treated individually whenever possible to ensure delivery of therapeutic levels of the drug and to prevent exposure of other animals. Sulfonamides may be used. Sulfaquinoxaline has been reported to give excellent clinical results. Amprolium has been reported to be effective during outbreaks in calves, sheep, and goats. Prevention: Continuous low-level feeding of amprolium, decoquinate, lasalocid, or monensin during the first month of feedlot confinement has been reported to have preventive value. Coccidiosis of Cats and Dogs Many species of coccidia infect the intestinal tract of cats and dogs. All species appear to be host-specific. Cats have species of Isospora , Besnoitia , Toxoplasma , Hammondia , and Sarcocystis . Dogs have species of Isospora , Hammondia , and Sarcocystis . Neither dogs nor cats have Eimeria . Hammondia has an obligatory two-host life cycle with cats or dogs as final hosts and rodents or ruminants as intermediate hosts, respectively. Hammondia oocysts are indistinguishable from those of Toxoplasma and Besnoitia but are nonpathogenic in either host. See also besnoitiosis, sarcocystosis, and toxoplasmosis. The most common coccidia of cats and dogs are Isospora . Almost every cat eventually becomes infected with I felis . The most common clinical signs in severe cases are diarrhea (sometimes bloody), weight loss, and dehydration. Usually, coccidiosis is associated with other infectious agents, immunosuppression, or stress. In kennel conditions when the need for prophylaxis might be predicted, amprolium is said to be effective, although it is not approved for use in dogs. In severe cases, in addition to supportive fluid therapy, sulfonamides such as sulfadimethoxine.
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Coccidiosis of Cattle Of the species of Eimeria that infect cattle, E zuernii , E bovis , and E auburnensis are most often associated with clinical disease. Experimentally, other species have been shown to be mildly or moderately pathogenic. Coccidiosis is commonly a disease of young cattle (1-2 mo to 1 yr) and usually is sporadic during the wet seasons of the year. The incubation period is 17-21 days. The most characteristic sign of clinical coccidiosis is watery feces, with little or no blood, and the animal shows only slight discomfort for a few days. Severe infections are rare. Severely affected cattle develop diarrhea, which consists of thin bloody fluid, that may continue for > 1 wk, or thin feces with streaks or clots of blood, shreds of epithelium, and mucus. Calves with concurrent infections (eg, coronavirus) may be more severely affected than calves with coccidia infections alone. In addition, management factors, such as weather, housing, feeding practices, and how animals are grouped, are important in determining the expression of clinical coccidiosis in cattle. The pathogenic coccidia of cattle can damage the mucosa of the lower small intestine, cecum, and colon. The firstgeneration schizonts of E bovis appear as white macroscopic bodies in the villi of the small intestine. Differential diagnoses include salmonellosis, bovine virus diarrhea, malnutrition, toxins, or other intestinal parasites. Coccidiosis of Goats The Eimeria spp are host-specific and are not transmitted from sheep to goats. Eimeria arloingi , E christenseni , and E ninakohlyakimovae are highly pathogenic in kids. Clinical signs include diarrhea with or without mucus or blood, dehydration, emaciation, weakness, anorexia, and death. Some goats are actually constipated and die acutely without diarrhea. Usually, stages and lesions are confined to the small intestine, which may appear congested, hemorrhagic, or ulcerated, and have scattered pale, yellow to white macroscopic plaques in the mucosa. Histologically, villous epithelium is sloughed, and inflammatory cells are seen in the lamina propria and submucosa. In addition, there have been several reports of hepatobiliary coccidiosis with liver failure in dairy goats. Coccidiosis of Pigs Eight species of Eimeria and one of Isospora infect pigs in the USA. Isospora suis is prevalent in neonatal pigs. Infection is characterized by a watery or greasy diarrhea, usually yellowish to white and foul smelling. Piglets may appear weak, dehydrated, and undersized; weight gains are depressed, and sometimes piglets die. A contributing factor to mortality is that piglets become covered with diarrheic feces and stay damp. Piglets that recover from infection are highly resistant to reinfection. Coccidiosis of Sheep Infections with some species of Eimeria are one of the most economically important diseases of sheep. The parasites are now considered host-specific. Cryptosporidiosis Cryptosporidiosis is an enterocolitis of cosmopolitan distribution caused by the coccidian parasite Cryptosporidium parvum . It is not host-specific and is common in young ruminants. The disease in calves, characterized by weight loss and watery diarrhea, is clinically indistinguishable from many other causes of calf diarrhea. Unless the immune system is compromised, it is self-limiting. Cryptosporidium parvum infections from animals and other people pose a significant risk to immunocompromised people, who can develop protracted diarrhea and die. Etiology and Transmission: Cryptosporidium parvum is a minute protozoan that is transmitted by the fecal-oral route. Clinical Findings and Lesions: Although C parvum can infect virtually the entire intestinal tract, the distal small intestine usually is affected most severely. Infection in horses is limited to the small intestine. Gross lesions may consist of hyperemic intestinal mucosa and yellowish intestinal contents. Microscopically, mild to severe villous atrophy with spherical organisms in the brush border is evident. Unlike Eimeria and Isospora spp , which are intracellular parasites, C parvum is intramembranous and resides within the brush border of the intestinal epithelial cells. Treatment and Control: There is no effective specific treatment; however, because the disease is self-limiting, supportive therapy, such as rehydration, correction of acidosis, and maintenance of energy requirements, is usually sufficient. Giardiasis: Introduction Giardiasis is a chronic, intestinal protozoal infection that occurs worldwide in most domestic and wild mammals, many birds, and people. There is circumstantial evidence that the Giardia spp that infect domestic animals can infect people.
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Etiology and Transmission: Flagellate protozoa (trophozoites) of the genus Giardia inhabit the mucosal surfaces of the small intestine, where they multiply by binary fission. Transmission occurs in the cyst stage by the fecal-oral route. Incubation and prepatent periods are generally 5-14 days. Cysts can survive in the environment but trophozoites cannot. Clinical Findings and Lesions: Giardia infections in dogs and cats may be inapparent or produce weight loss and chronic diarrhea or steatorrhea, which can be continuous or intermittent, particularly in puppies and kittens. Clinical giardiasis has been reported in calves. Giardiasis must be differentiated from other causes of nutrient malassimilation (eg, exocrine pancreatic insufficiency, intestinal malabsorption. Diagnosis: Because Giardia are excreted intermittently, several fecal examinations should be performed if giardiasis is suspected. Treatment: No drugs are approved for treating giardiasis in animals. Albendazole and fenbendazole have effectively cleared Giardia cysts from the feces of infected dogs and cats. No side effects are reported; however, albendazole is not approved for use in cats and dogs, and because it is suspected of being teratogenic, should not be administered to pregnant animals. Fenbendazole at 50 mg/kg/day, PO, for 3 days, effectively removes Giardia cysts from the feces of dogs; no side effects are reported, and it is safe for pregnant and lactating animals. Anal Sac Disease Anal sac disease is the most common disease entity of the anal region in dogs. Small breeds are predisposed; large or giant breeds are rarely affected. In cats, the most common form of anal sac disease is impaction. Etiology and Pathogenesis: Anal sacs may become impacted, infected, abscessed, or neoplastic. Failure of the sacs to express during defecation, poor muscle tone in obese dogs, and generalized seborrhea (which produces glandular hypersecretion) lead to retention of sac contents. Such retention may predispose to fermentation, inflammation, and secondary bacterial infection. Clinical Findings, Lesions, and Diagnosis: Signs are related to pain and discomfort associated with sitting. Scooting, licking, biting at the anal area, and painful defecation with tenesmus are also common. Induration, abscesses, and fistulous tracts are common. In impaction, hard masses are palpable in the area of the sacs; the sacs are packed with a thick, pasty, brown secretion, which can be expressed as a thin ribbon only with a large amount of pressure. When the sacs are infected or abscessed, severe pain and often discoloration of the area are present. Fistulous tracts lead from abscessed sacs and rupture through the skin; these must be differentiated from perianal fistulas. Anal sac neoplasms are usually nonpainful and are associated with perineal edema, erythema, induration, or fistula formation. Apocrine gland adenocarcinomas of the anal sac occur typically in older female dogs. These dogs are presented for signs secondary to hypercalcemia, such as polyuria and polydipsia, or for problems related to the perineal mass. Diagnosis of impaction, infection, or abscessation is confirmed by digital rectal examination, at which time the sacs can be expressed. Microscopical examination of the contents from infected sacs reveals large numbers of polymorphonuclear leukocytes and bacteria. A tumor should be suspected (anal sac apocrine adenocarcinoma) in anal sacs that are firm, enlarged, and nonexpressible even with irrigation. In these cases, the diagnosis should be confirmed by biopsy. Regional and systemic metastasis should be evaluated and serum calcium assessed. Treatment: Impacted anal sacs should be gently manually expressed. A softening or ceruminolytic agent can be infused into the sac if the contents are too dry to express effectively. Infected sacs should be cleaned with antiseptic, followed by local and systemic antibiotic therapy. Repeated weekly flushings combined with infusion of a steroid-antibiotic ointment may be needed. If medical treatment is ineffective, or if neoplasia is present, surgical excision of the sac is indicated. However, fecal incontinence, which is a common complication of anal sac surgery, may result from damage to the caudal rectal branch of the pudendal nerve and may be complete if damage is bilateral. Scar formation in the external anal sphincter may result from surgical trauma and may produce tenesmus. Perineal Hernia Perineal hernia is a lateral protrusion of a peritoneally lined hernial sac between the levator ani and either the external anal sphincter muscle or the coccygeus muscle. Incidence in intact 6- to 8-yr old male dogs. Etiology and Pathogenesis: Many factors are involved, including breed predisposition, hormonal imbalance, prostatic disease, chronic constipation, and weakness of the pelvic diaphragm due to chronic straining. The higher incidence among sexually intact males is evidence that hormonal influences probably play a primary role. Prostatic hypertrophy attributed to sex-hormone imbalance has been strongly implicated. Both estrogens and androgens have been cited as causative agents.
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Clinical Findings and Diagnosis: Common signs include constipation and obstipation, tenesmus, and dyschezia. Stranguria may occur secondary to retroflexion of the bladder and prostate. A perineal swelling ventrolateral to the anus is evident. Herniation may be bilateral, but two-thirds are unilateral and >80% of these are on the right side. The mass is soft and fluctuant and may be reduced digitally. A firm, painful swelling may be compatible with retropulsion of the bladder and prostate. Determination of contents is often made by rectal examination. Over 90% of perineal hernias contain a rectal deviation, which is a sacculation of the rectum into the hernial sac, where the layers of the rectal wall remain intact. Treatment: Perineal hernia is rarely an emergency, except when the bladder has strangulated and the animal is unable to urinate. Rectal Prolapse In rectal prolapse, one or more layers of the rectum protrude through the anus due to persistent tenesmus associated with intestinal, anorectal, or urogenital disease. Prolapse may be classified as incomplete, in which only the rectal mucosa is everted, or complete, in which all rectal layers are protruded. Etiology: Rectal prolapse is common in young animals in association with severe diarrhea and tenesmus. Causal factors include severe enteritis, disorders of the rectum (eg, foreign bodies, lacerations, diverticula, or sacculation), neoplasia of the rectum or distal colon, urolithiasis, urethral obstruction, cystitis, dystocia, colitis, and prostatic disease. Rectal prolapse is probably the most common GI problem in pigs due to diarrhea or weakness of the rectal support tissue within the pelvis. In cattle, it may be associated with coccidiosis, rabies, or vaginal or uterine prolapse; occasionally, excessive “riding” and associated traumatic injury may be causative in young bulls. It is common in sheep with short tail docking or especially in feedlot lambs, in which high-concentrate rations may be causative. Clinical Findings, Lesions, and Diagnosis: An elongated, cylindrical mass protruding through the anal orifice is usually diagnostic. However, it must be differentiated from prolapsed ileocolic intussusception by passing a probe, blunt instrument, or finger between the prolapsed mass and the inner rectal wall. In rectal prolapse, the instrument cannot be inserted due to the presence of a fornix. Ulceration, inflammation, and congestion of the rectal mucosa is common. Early, there is a short, nonulcerated, inflamed segment; later, the mucosal surface darkens and may become congested and necrotic. Treatment: In all animals, identifying and eliminating the cause is of primary importance. In small animals, treatment includes prompt replacement of viable prolapsed tissue to its proper anatomic location, or amputation if the segment is necrotic. Small or incomplete prolapses can be manually reduced under anesthesia by using a finger or bougie. Hypertonic sugar solution (50% dextrose or 70% mannitol) applied directly to the mucosa relieves edema and eases reduction. The placement of a loose, anal purse-string suture for 5-7 days is indicated. Postoperatively, a moistened diet and a fecal softener (eg, dioctyl sodium sulfosuccinate) are recommended. In large animals, caudal epidural anesthesia is suggested to reduce straining, facilitate repositioning of the prolapse, and permit surgical manipulations. Reduction and retention with a purse-string suture is recommended. The suture should be loose enough to leave a one-finger opening into the rectum in pigs and sheep, and slightly larger in cattle and horses. Rectal Tears A separation, rent, or tear in the rectal or anal mucosa occurs as a result of a laceration inflicted within the lumen. Foreign bodies (eg, sharp bones, needles, and other rough material) have been implicated. Clinical Findings and Diagnosis: Constipation and reluctance to defecate are usually attributed to pain. Diagnosis is based on tenesmus and hemorrhage, perineal discoloration, and inspection of the rectum and anus; fresh blood found on a glove or on feces after rectal examination is good evidence of a rectal tear. Treatment: In all species, treatment should be initiated immediately. In cattle and horses, accidental perforation during rectal examination necessitates immediate treatment to reduce the risk of peritonitis and death. Rectal tears in horses have been classified according to the tissue layers penetrated. Grade I tears involve the mucosa or submucosa. Grade II tears involve rupture of the muscular layers only. Grade III tears involve mucosa, submucosa, and muscular layers, including tears that extend into the mesorectum. Grade IV tears involve perforation of all layers of the rectum and extension into the peritoneal cavity. Grade I tears may be treated conservatively with broad-spectrum antibiotics and IV fluids. Flunixin meglumine may be given to prevent or treat endotoxic shock. Mineral oil is given via stomach tube to soften feces, and the diet should consist of pasture grasses or alfalfa. Grade II and III tears require immediate and more extensive surgery. Grade IV tears carry a

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grave prognosis; they should be repaired only if small and if treatment is instituted before the peritoneal cavity is grossly contaminated. Abomasal Disorders: Introduction Abomasal disorders include left displaced abomasum (LDA), right displaced abomasum (RDA), abomasal volvulus, ulcers, and impaction. Displacement or volvulus occurs commonly in dairy cows, particularly high-producers, but also in bulls, calves, and small ruminants. They are rare in beef cattle. Left or Right Displaced Abomasum and Abomasal Volvulus Because the abomasum is suspended loosely by the greater and lesser omenta, it can be moved from its normal position on the right ventral part of the abdomen to the left or right side (LDA, RDA), or it can rotate on its mesenteric axis while displaced to the right (abomasal volvulus). Abomasal volvulus can develop rapidly or slowly from an uncorrected RDA. Etiology: The etiology is multifactorial, although abomasal atony and gas production contribute to development of displacement or volvulus. Atony is related to high-concentrate, low-roughage diets, which result in increased production of volatile fatty acids, high concentrations of which reduce abomasal motility. Other contributing factors include decreased abomasal motility associated with hypocalcemia, concurrent diseases (mastitis, metritis, and ketosis), changes in position of intra-abdominal organs, and genetic predisposition. About 80% of displacements occur within 1 mo of parturition; however, they can occur any time. LDA is much more common than RDA (8:1), and cases of volvulus are even less frequent (25 LDA to 1 volvulus). Pathogenesis: A mild metabolic alkalosis with hypochloremia and hypokalemia are common. The hypochloremic metabolic alkalosis is probably due to abomasal atony, continued secretion of hydrochloric acid into the abomasum, and the partial abomasal outflow obstruction, with sequestration of chloride in the abomasum and reflux into the rumen as a result. Hypokalemia is probably due to decreased intake of feeds high in potassium and to continued renal secretion of potassium. Secondary ketosis is common and may be complicated by development of fatty liver disease. A large quantity of fluid accumulates in the abomasum; chloride is sequestered there as well. Hypochloremic, hypokalemic metabolic alkalosis develops. The blood supply to the abomasum, and often the omasum, is compromised, eventually resulting in ischemic necrosis of the abomasum as well as dehydration and circulatory failure. As this progresses, a metabolic acidosis is superimposed on the metabolic alkalosis. Clinical Findings: The most important diagnostic physical finding is a ping on simultaneous auscultation and percussion of the abdomen, which should be performed in the area marked by a line from the tuber coxae to the point of the elbow, and from the elbow toward the stifle. The ping characteristic of an LDA is most commonly located in an area between ribs 9 and 13 in the middle to upper third of the abdomen; however, the ping can be more ventral or more caudal, or both. Pings associated with a rumen gas cap or rumen collapse are usually more dorsal, less resonant, and extend more caudally through the paralumbar fossa. Pings associated with pneumoperitoneum typically are less resonant, present on both sides of the abdomen, and inconsistent in location on repeated evaluation. The ping associated with RDA also is most commonly located in the area between ribs 9 and 13. Differentiation between various causes of a right-sided ping is difficult in some cases. A small ping underlying ribs 12 or 13 and extending as far forward as rib 10 is common in cows with functional ileus from a number of causes. It is most often associated with gas in the ascending colon and resolves with correction of the underlying condition. Palpation per rectum is helpful in differentiating an RDA from cecal dilatation or rotation. Other right-sided pings are produced by pneumoperitoneum or gas in the rectum, descending colon, duodenum, or occasionally in the ventral sac of the rumen (with chronic vagal indigestion). The characteristic rectal examination findings with LDA include a medially displaced rumen and left kidney. The abomasum is rarely palpable in LDA and only occasionally in RDA. An early abomasal volvulus is indistinguishable from an RDA except by the anatomic position identified at surgery. In contrast with cases of displacement, an animal with abomasal volvulus has tachycardia proportional to the severity of the condition. Diagnosis: For displacement or volvulus, diagnosis is based on the presence of the characteristic ping on simultaneous auscultation and percussion and ruling out other causes of left- or right-sided pings. Recent parturition, partial anorexia, and decreased milk production suggest displacement. A ketosis that is only temporarily responsive to treatment is consistent with abomasal displacement, which may be intermittent. The typical signs on physical examination (in addition to the ping), rectal examination, and laboratory evaluation also support the diagnosis. Melena or signs of peritonitis (eg, fever, tachycardia,

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localized abdominal pain, pneumoperitoneum) with an LDA may indicate a bleeding or perforated abomasal ulcer, respectively. Treatment: Closed (percutaneous) or open (surgical) techniques can be used to correct displacements. Rolling a cow through a 70°arc after casting her on her right side corrects most LDA; however, recurrence is likely. LDA can be corrected surgically using right paramedian abomasopexy, right paralumbar fossa omentopexy, or left paralumbar abomasopexy. Toggle-pin fixation or the blind-stitch technique, both performed in the right paramedian area, are percutaneous methods for correction of LDA. With toggle-pin fixation, the pH can be checked to confirm that the pin is in the abomasum, which reduces the likelihood of attaching rumen, small intestine, or omentum to the body wall rather than the abomasum. RDA and abomasal volvulus are corrected surgically (right paralumbar fossa omentopexy or right paramedian abomasopexy) when economically feasible. Calcium borogluconate SC helps restore normal abomasal motility in many cases. Occasionally, animals with abomasal displacement or volvulus will have atrial fibrillation, thought to be of metabolic or neurogenic origin. It is characterized by an irregularly irregular cardiac rhythm with pulse deficits. Correction of the displacement or volvulus results in correction of the atrial fibrillation, although some cases do not resolve for ≥1 mo. The prognosis after correction of simple LDA or RDA is good, with reported success of 75-95%. Volvulus has a variable and less favorable prognosis; a large quantity of fluid in the abomasum, a high anion gap, a high heart rate, a low plasma chloride concentration, and metabolic acidosis are associated with a poor prognosis. Prevention: feeding a complete ration rather than feeding grain twice daily, maintaining adequate roughage in the diet, avoiding postparturient hypocalcemia, and minimizing and promptly treating concurrent disease. Abomasal Ulcers Abomasal ulcers affect mature cattle and calves and have several different manifestations. Etiology and Pathogenesis: Except for lymphosarcoma of the abomasum and the erosions of the abomasal mucosa that occur with viral diseases such as bovine viral diarrhea, rinderpest, and bovine malignant catarrhal fever, the causes of abomasal ulceration are not well understood. Many different causes have been suggested. Although abomasal ulcers can occur any time during lactation, they are common in high-producing, mature dairy cows within the first 6 wk after parturition. This has led to speculation that the cause is a combination of the stress of parturition, the onset of lactation, and heavy grain feeding. Abomasal ulcers are common in hand-fed calves after they are weaned from milk or milk replacer and begin to eat roughage. Most of these are subclinical and nonhemorrhagic. They may be due to consumption of dry food. Occasionally, milk-fed calves <2 wk old are affected by acute, hemorrhagic abomasal ulcers that may perforate and cause rapid death. Clinical Findings: A system of classification is based on the depth of penetration or the degree of hemorrhage or peritonitis caused by the ulcer: Type I is an erosion or ulcer without hemorrhage, Type II is hemorrhagic, Type III is perforated with acute localized peritonitis, and Type IV is perforated with acute diffuse peritonitis. There may be only a single ulcer or many acute and chronic ulcers. Cattle with bleeding abomasal ulcers may be asymptomatic except for intermittent occult blood in the feces, or they can die acutely from massive hemorrhage. Common clinical signs include mild abdominal pain, bruxism, sudden onset of anorexia, tachycardia (90-100 beats/min), and fecal occult blood or melena that may be intermittent. Signs of blood loss occur with major hemorrhage and may include tachycardia (100-140 beats/min), pale mucous membranes, weak pulse, cool extremities, shallow breaths, tachypnea, and melena. Lesions: Ulceration is most common along the greater curvature of the abomasum. Most of the ulcers occur on the ventral part of the fundic region, with a few on the border between the fundic and pyloric regions. The single or multiple ulcers measure from a few millimeters to 5 cm in diameter. Multiple trichobezoars are common in the abomasum of beef calves with abomasal ulcers. Diagnosis: In cases with only slight bleeding and mild clinical signs, diagnosis may require repeated fecal evaluations for occult blood. Other conditions that can cause partial anorexia and decreased milk production should be ruled out by physical examination and laboratory tests, including abdominocentesis. In cases with melena, the diagnosis can be based on physical examination alone. The PCV can help to determine the degree of hemorrhage. Blood from portions of the GI tract distal to the abomasum reacts on fecal occult blood tests; it is usually bright red if from the large intestine or raspberry-colored if from the small intestine. Animals with abomasal lymphosarcoma can have a bleeding syndrome similar to that associated with abomasal ulcers but do not respond to therapy. Occasionally, oral, pharyngeal, and laryngeal lesions bleed, and the blood is swallowed and appears in the feces. Diagnosis of perforating abomasal ulcers is based on physical examination and ruling out other causes of peritonitis.
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Treatment: Most cases of abomasal ulcers are treated medically. This includes dietary management, primarily withholding concentrates (eg, high-moisture corn, silage, and concentrates that are finely ground) and providing good-quality roughage, as well as stall confinement and elimination of other sources of stress. Broad-spectrum antibiotic therapy (continued for 1-2 wk or until the rectal temperature is normal for 48 hr) is indicated for perforating ulcers. The use of antacids is controversial but seems to be effective in some cases. Because nonsteroidal anti-inflammatory drugs can contribute to ulceration, their use is contraindicated. The prognosis for localized peritonitis associated with perforating abomasal ulcers is good with medical therapy and dietary alteration. Usually, surgery is indicated for perforating abomasal ulcers only if the abomasum is displaced; however, significant abdominal contamination can occur in the process of breaking down adhesions and resecting or oversewing the ulcer. Corticosteroids are sometimes used in nonpregnant animals initially to counteract shock but should not be continued. The few animals that recover from diffuse peritonitis usually have massive abdominal adhesions. For bleeding ulcers, blood transfusions and fluid therapy may be necessary in addition to dietary management, stall confinement, and oral antacids. If hemorrhage is acute, the PCV may not reflect the severity because equilibration between intravascular and extravascular fluid after blood loss takes ~24 hr. Prevention: Minimizing stress by good management practices (adequate space, ventilation, access to water, etc) and by providing a diet with sufficient roughage and concentrates with larger particle size reduces the incidence. Dietary Abomasal Impaction Impaction of the abomasum occurs during cold winter months and when cattle are fed poor-quality roughage. It is most common in pregnant beef cattle that increase their intake of low-quality roughage during extremely cold weather in an attempt to meet increased energy needs. Etiology: The cause is considered to be consumption of excess roughage that is low in both digestible protein and energy. Impaction with sand can occur if cattle are fed hay or silage on sandy soils, or root crops that are sandy or dirty. When long roughage without sufficient grain is fed during very cold weather, the cattle cannot eat enough to satisfy energy needs, so roughage may then be chopped. Pathogenesis: When large quantities of sand are ingested, the omasum, abomasum, large intestine, and cecum can become impacted. The sand that accumulates in the abomasum causes abomasal atony and chronic dilatation. Once the abomasum becomes impacted, subacute obstruction of the upper GI tract develops. Ions of hydrogen and chloride are continually secreted into the abomasum in spite of the impaction, and atony and alkalosis with hypochloremia result. Varying degrees of dehydration occur because fluids are not moving beyond the abomasum into the duodenum for absorption. Sequestration of potassium ions in the abomasum results in hypokalemia. Dehydration, alkalosis, electrolyte imbalance, and progressive starvation occur. Impaction of the abomasum may be severe enough to cause irreversible abomasal atony. Clinical Findings and Lesions: Usually, the muzzle is dry and cracked due to the failure of the animal to lick its nostrils and to the effects of dehydration. The heart rate may be increased, and mild dehydration is common. Most often, the rumen is static and distended with dry contents, but it may contain excess fluid if the cow has been fed finely ground feed. The pH of the ruminal fluid is usually normal (6.5-7). Protozoal activity in the rumen ranges from normal to a marked reduction in numbers and activity (assessed microscopically under low power). Severely affected cattle die 3-6 days after the onset of signs. The abomasum ruptures in some cases, and death from acute, diffuse peritonitis and shock occurs precipitously in a few hours. In sand impaction, there is considerable weight loss, chronic diarrhea with sand in the feces, weakness, recumbency, and death in a few weeks. Metabolic alkalosis, hypochloremia, hypokalemia, hemoconcentration, and total and differential WBC counts within the normal range are common. If the abomasum has ruptured, lesions of acute diffuse peritonitis are present. Diagnosis: Clinical diagnosis is based on the nutritional history, clinical evidence of impaction, and laboratory results. The disease must be differentiated from secondary abomasal impaction as a form of vagal indigestion or from omasal impaction. Treatment: The challenge is to recognize the cases that will respond to treatment and those that will not, ie, to determine those that should be slaughtered immediately for salvage. Cows with a severely impacted abomasum, that are weak, and have a marked tachycardia (100-120 beats/min) are poor treatment risks. In cows that are treated, the metabolic alkalosis, hypochloremia, hypokalemia, and dehydration should be corrected; lubricants and cathartics can be used in an attempt to move the impacted material, or the abomasum should be emptied surgically. Balanced electrolyte solutions are infused IV continuously for up to 72 hr at a daily rate of 100-130 mL/kg body wt. Some cows respond well to this therapy and begin ruminating and passing feces in 48 hr.
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Dioctyl sodium sulfosuccinate (DSS) is given by stomach tube Mineral oil and DSS should not be administered simultaneously because DSS may potentiate the absorption of mineral oil. Surgery may be considered, but results are often unsuccessful, probably because of abomasal atony, which appears to worsen after surgery. An alternative may be to do a rumenotomy, empty the rumen, and infuse DSS directly into the abomasum through the reticulo-omasal orifice in an attempt to soften and promote the evacuation of the contents of the abomasum. Cattle with secondary impactions that occur as a sequela of traumatic reticuloperitonitis or abomasal volvulus usually show signs of vagal indigestion, and abomasal impaction may be diagnosed at the time of exploratory surgery. The induction of parturition using dexamethasone (20 mg, IM) may be indicated in affected cattle within 2 wk of term and in which the response to treatment for a few days has been unsuccessful. Parturition may assist recovery because of a reduction in intra-abdominal volume. For sand impaction, affected cattle should be moved off the sandy soil and fed good hay and a grass mixture containing molasses and minerals. Severely affected cattle should be treated with large doses of mineral oil (≥3.75 gal. [15 L]/day). Control: Allowances should be made for cold, windy weather when energy needs may be 30-40% greater than during warm weather. When low-quality roughage is used for wintering pregnant beef cattle, it should be analyzed for crude protein and digestible energy. Based on the analysis, grain is usually added to the ration to meet the energy and protein requirements. Forcing wintering cows to obtain their water requirements by eating snow while on low-quality roughage is hazardous. Whether low-quality roughages should be chopped or ground for wintering pregnant beef cattle is controversial. Bovine Viral Diarrhea And Mucosal Disease Complex: Introduction Bovine viral diarrhea virus (BVDV) is classified as a pestivirus (family Flaviviridae) and is antigenically related to hog cholera virus and border disease virus of sheep. Although cattle are the primary host for BVDV, the virus infects most eventoed ungulates. All BVDV are related antigenically, and separate serotypes of virus have not been identified, but there are two viral biotypes—noncytopathic and cytopathic. Classification of viral biotype is based on cytopathic effect in cultured cells and is not related to virulence. Noncytopathic BVDV are common in cattle. The cytopathic biotype is relatively rare and arises from noncytopathic BVDV after a specific (and rare) mutational event occurs in the viral genome. Etiology and Epidemiology: All ages of cattle are susceptible, but infection usually occurs between 6 and 24 mo of age. Colostral antibody appears to protect most calves for 3-6 mo after birth. The natural reservoir for BVDV is persistently infected cattle. Noncytopathic BVDV is transmitted transplacentally during the first 4 mo of fetal development; therefore, infection is present at birth and lasts for life. The incidence of persistent infection is 1-2% in most countries. Infected cattle are often clustered within a specific age group on a specific farm. Large numbers of BVDV are shed in the secretions and excretions of persistently infected cattle. Clinical disease and reproductive failure are reported in healthy cattle after contact with a persistently infected animal. BVDV may also be spread (rarely) through biting insects, wild ruminants, or fomites. Clinical Findings and Lesions: Diseases induced by BVDV vary in severity, duration, and organ systems involved. Acute disease results from infection of susceptible cattle of any age with either noncytopathic or cytopathic BVDV. Biphasic fever (~104° F [40°C]), depression, decreased milk production, and inappetence are typical signs of acute BVD. An increased respiratory rate, diarrhea, and excessive lacrimation may be seen. Disease occurs 7-14 days after infection, lasts for 1-3 days, and is followed by rapid recovery with production of viral neutralizing antibody. Gross lesions are seldom seen in mild forms of acute disease; however, transient leukopenia is common. The virus replicates in lymphoid cells and suppresses certain mononuclear and polymorphonuclear leukocyte functions. Some noncytopathic BVDV induce clinically severe disease with a high fever (~107° F [41-42°C]), oral ulcerations, eruptive lesions of the coronary band and interdigital cleft, diarrhea, dehydration, leukopenia, and thrombocytopenia. In thrombocytopenic cattle, petechial hemorrhages may be seen in the conjunctiva, sclera, nictitating membrane, and mouth. Swollen lymph nodes, erosions and ulcerations of the GI tract, petechial and ecchymotic hemorrhages on the serosal surfaces of the viscera, and lymphoid depletion are findings associated with severe forms of acute disease. The duration of disease may be several days, morbidity may be high, and mortality may exceed 20%. BVDV may cross the placenta and infect the fetus in pregnant cattle that experience mild or severe forms of acute disease. The consequences of fetal infection usually are not seen until several weeks to months after the dam is infected. The effects on the fetus appear dependent on viral strain and stage of fetal development when infection occurs. Infection during the first 4 mo of fetal development may cause embryonic resorption, abortion, intrauterine growth retardation, and persistent infection. Congenital malformations of the eye and CNS result from fetal infections that occur between the fourth and sixth months of development. Fetal mummification, premature birth, stillbirth, and birth of weak calves also occur after fetal infection. Persistent infection is an important sequela of fetal infection. Persistently infected calves can appear healthy or show clinical signs that include stunted growth and frequent respiratory or enteric ailments. The life span of persistently infected
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cattle often is≤2 yr. Lesions attributable to BVDV may not be seen at necropsy. Persistently infected cows that reproduce give birth to persistently infected calves. Persistent infection is induced before the fetus becomes immunocompetent and results in an immunotolerance that is restricted to the homologous virus. Thus, antibody against the persistent virus is not detected. Acute and chronic mucosal disease are highly fatal forms of BVD seen in persistently infected cattle. These diseases occur when persistently infected cattle become superinfected with cytopathic BVDV. The origin of the cytopathic BVDV is usually internal, resulting from mutation of the persistent noncytopathic BVDV. External origins for cytopathic BVDV include other cattle and modified live virus vaccines. Because persistent infection is relatively rare, morbidity for mucosal disease is low. Acute mucosal disease is characterized by fever, leukopenia, diarrhea, inappetence, dehydration, erosive lesions of the nares and mouth, and death within a few days of onset. At necropsy, erosions and ulcerations may be found throughout the GI tract. Clinical signs of chronic mucosal disease may last several weeks to months and are less severe than those of acute mucosal disease. Diagnosis: Bovine viral diarrhea can be tentatively diagnosed from the history, clinical signs, and gross and microscopic lesions. Diagnostic laboratory support is required when clinical signs and gross lesions are minimal and is essential in some outbreaks of mucosal disease or clinically severe acute bovine viral diarrhea, which can appear similar to rinderpest and malignant catarrhal fever. Laboratory tests for BVDV detect antibody, viral antigen, or viral RNA. Because antibody against BVDV is prevalent in most cattle populations, a single serologic test is seldom sufficient for diagnosis. Frequently, paired serum samples that show a four-fold or greater increase in antibody titer is necessary to detect recent infection. Active infection is confirmed by isolation and identification of virus from blood or nasal swab specimens. Identification of persistent infection requires isolation of virus from clinical samples or from blood or nasal swabs obtained at least 3 wk apart. At necropsy, tissues of choice for viral isolation include spleen, lymph node, and segments of the GI tract that contain ulcerative lesions. Control: Treatment is limited. Supportive therapy and administration of antiserum may be of benefit in outbreaks of acute disease. Both inactivated and modified live virus vaccines are available. Because BVDV is immunosuppressive and fetotropic, modified live virus vaccines should be used in cattle that are healthy and not pregnant. Inactivated vaccines are safe to use in pregnant cattle, but initial immunization usually requires administration of two doses of vaccine several weeks apart. Ideally, female cattle should be vaccinated before breeding age to minimize the risk of their fetuses becoming infected in utero. Colic In Horses: Introduction In its strictest definition, the term “colic” means abdominal pain. Relevant Gastrointestinal Anatomy: Presumably due to the abrupt decrease in diameter, the junction between the left ventral colon and pelvic flexure is the most common location for impactions. The diameter of the left dorsal colon is maximal either at its diaphragmatic flexure or at the right dorsal colon. Blood Supply to the GI Tract: The celiac artery supplies arterial blood to the stomach, pancreas, liver, spleen, and the first portion of the duodenum. The cranial mesenteric artery supplies arterial blood to the remaining portion of the duodenum; to all of the jejunum, ileum, cecum, large colon, and transverse colon; and to the first portion of the descending colon. Because the large colon is attached to the body wall only in the region immediately surrounding the cranial mesenteric artery, the blood supplying all portions of the colon must traverse the entire length of the colon. The pelvic flexure receives its blood supply from two branches of the cranial mesenteric artery; one branch supplies the right dorsal and left dorsal colons before reaching the pelvic flexure, and the other branch supplies the right and left ventral colons before reaching the pelvic flexure. Thus, volvulus of the large colon near the junction of the colon and cecum may impede the flow of blood to the entire left colon. The major branches of the cranial mesenteric artery can be damaged by the migrating forms of Strongylus vulgaris (see Large Strongyles ). Natural Openings in the Abdomen: There are several natural openings or spaces within the abdominal cavity that can be important in conditions causing colic. The inguinal canal provides an opening through which intestine might pass and become trapped. Although inguinal hernias are common in young foals, they rarely cause clinical problems; the situation is considerably different in stallions. Similarly, if the ventral abdominal wall fails to form properly around the umbilicus, an opening remains and the potential exists for intestinal problems to occur secondary to an umbilical hernia. The epiploic foramen, a natural opening between the portal vein, the caudal vena cava, and the caudate lobe of the liver, can be the site for intestinal incarcerations, particularly
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in horses >7 yr old. Finally, there is a natural space between the dorsal aspect of the spleen and the left kidney. This space is bounded by the nephrosplenic ligament, a strong band of tissue that connects the dorsomedial aspect of the spleen with the fibrous capsule of the left kidney. This ligament provides a “shelf” over which large colon can be displaced. Colonic Motility Patterns: Normograde peristalsis in the left ventral colon moves ingesta toward the left dorsal colon, and the muscles in the wall of the left dorsal colon contract to move the ingesta toward the diaphragmatic flexure. Clinical Findings and Diagnosis: Numerous clinical signs are associated with colic. The most common include pawing repeatedly with a front foot, looking back at the flank region, curling the upper lip and arching the neck, repeatedly raising a rear leg or kicking at the abdomen, lying down, rolling from side to side, sweating, stretching out as if to urinate, straining to defecate, distention of the abdomen, loss of appetite, and decreased number of bowel movements. It is uncommon for a horse with colic to exhibit all of these signs. Although these clinical signs are reliable indicators of abdominal pain, the particular signs do not indicate which portion of the GI tract is involved or whether surgery will be needed. In most instances, colic occurs for one of four reasons: 1) The wall of the intestine is stretched excessively either by gas, fluid, or ingesta. This stimulates the stretch-sensitive nerve endings located within the intestinal wall, and pain impulses are transmitted to the brain. 2) Pain develops if there is excessive tension on the mesentery. 3) Ischemia develops, most often as a result of incarceration or severe twisting of the intestine. 4) Inflammation develops and may involve either the entire intestinal wall (enteritis) or the covering of the intestine (peritonitis). Under such circumstances, proinflammatory mediators in the wall of the intestine decrease the threshold for painful stimuli. The list of possible conditions that cause colic is long, and it is reasonable first to determine the most likely type of disease and begin appropriate treatments and then to make the more specific diagnosis, if possible. The general types of disease that cause colic include excessive gas in the intestinal lumen (flatulent colic), simple obstruction of the intestinal lumen, obstruction of both the intestinal lumen and the blood supply to the intestine (strangulating obstruction), interruption of the blood supply to the intestine alone (nonstrangulating infarction), inflammation of the intestine (enteritis), inflammation of the lining of the abdominal cavity (peritonitis), erosion of the intestinal lining (ulceration), and “unexplained colic.” In general, horses with strangulating obstructions and certain simple obstructions require emergency abdominal surgery, whereas horses with the other types of disease can be treated medically. The diagnostic approach must be thorough and systematic. The history of the present colic episode and previous episodes, if any, must be ascertained to determine if the horse has had repeated or similar problems, or if this episode is an isolated event. The duration of the episode, the rate of deterioration of cardiovascular status, the severity of the pain, whether feces have been passed, and the response to treatment are important information. The physical examination should include assessment of the cardiopulmonary and GI systems. The oral mucous membranes should be evaluated for color, moistness, and capillary refill time. The mucous membranes may become cyanotic or pale in acute cardiovascular compromise and eventually hyperemic or muddy as peripheral vasodilation develops later in shock. The capillary refill time (normal ~1.5 sec) may be shortened early but usually becomes prolonged as vascular stasis (venous pooling) occurs. The membranes will become dry as the horse becomes dehydrated. The heart rate increases due to pain, hemoconcentration, and hypotension; therefore, higher heart rates have been associated with more severe intestinal problems (strangulation obstruction). However, not all conditions requiring surgery are accompanied by a high heart rate. An important aspect of the physical examination is passing a nasogastric tube. Because horses can neither regurgitate nor vomit, adynamic ileus, obstructions involving the small intestine, or distention of the stomach with gas or fluid may result in gastric rupture. Passing a stomach tube may, therefore, save the horse's life and assist in diagnosis of these conditions. If fluid reflux occurs, the volume and color of the fluid should be noted. The abdomen and thorax should be ausculted, and the abdomen percussed. The complete lack of sounds is usually associated with adynamic ileus or ischemia. Percussion will assist in identifying a grossly distended segment of intestine (cecum on right, colon on left) that may need to be trocarized. The respiratory rate may be increased due to fever, pain, acidosis, or an underlying respiratory problem. Diaphragmatic hernia is also a possible cause of colic. The most definitive part of the examination is the rectal examination. A sample of peritoneal fluid (obtained via paracentesis performed aseptically on midline) often reflects the degree of intestinal damage. The color, cell count and differential, and total protein concentration should be evaluated. Normal peritoneal fluid is clear to straw-colored, contains <5,000 WBC/µL, most of which are mononuclear cells, and <2.5 g of protein/dL. The age of the horse is important because a number of age-related conditions cause colic. The more common of these include the following: in foals—atresia coli, meconium retention, uroperitoneum, and gastroduodenal ulcers; in yearlings— ascarid impaction; in the young—small-intestinal intussusception, nonstrangulating infarction, and foreign body

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obstruction; in the middle-aged—epiploic foramen, cecal impaction, enteroliths, and large-colon volvulus; and in the aged —pedunculated lipoma and mesocolic rupture. Treatment: Horses with colic may need either medical or surgical treatments. Almost all require some form of medical treatment, but only those with certain mechanical obstructions of the intestine need surgery. Fortunately, the number that need surgery is a small proportion of the total number of horses with colic. The type of medical treatment is determined by the cause of colic and the severity of the disease. In some instances, the horse may be treated medically first and the response evaluated; this is particularly appropriate if the horse is mildly painful and the cardiovascular system is functioning normally. If necessary, surgery can be used in such cases for a diagnosis as well as a treatment. If evidence of intestinal obstruction with dry ingesta is found on rectal examination, a primary aim of treatment is to hydrate and evacuate the intestinal contents. If the horse is severely painful and has clinical signs indicating loss of fluid from the bloodstream (high heart rate, prolonged capillary refill time, and discoloration of the mucous membranes), the initial aims of treatment are to relieve pain, restore tissue perfusion, and correct any abnormalities in the composition of the blood and body fluids. If damage to the intestinal wall (as a result of either severe inflammation or a displacement or strangulation obstruction) is suspected, steps should be taken to prevent or counteract the ill effects of bacterial endotoxins that leave the intestine and enter the bloodstream. Finally, if there is evidence that the colic episode is caused by parasites, one aim of treatment is to eliminate the parasites. Pain Relief: In most cases of colic, pain is mild, and analgesia is all that is needed. If, however, the pain is due to an intestinal twist or displacement, some of the stronger analgesics may mask the clinical signs that would be useful in making a diagnosis. Two medications used commonly for abdominal pain are dipyrone and flunixin meglumine. These nonsteroidal antiinflammatory drugs reduce the production of prostaglandins. Unlike dipyrone, flunixin may mask the early signs of conditions that require surgery and, therefore, must be used carefully in horses with colic. The most commonly used sedative for colic is xylazine, an α-2 agonist. Within a few minutes after administration, the horse stands quietly and is less responsive to pain. Unfortunately, the effects of xylazine are short-lived, and it inhibits the intestinal muscles; it also decreases cardiac output and thus reduces blood flow to the tissues. Detomidine, a more potent α2 agonist that is much longer-acting, is being used successfully under similar circumstances. Of the narcotic analgesics, butorphanol is used most often in horses with colic. Butorphanol has few adverse effects on the GI tract or heart. However, when given in large doses, narcotics can cause excitement, and the horse may become unstable. Butorphanol is frequently combined with xylazine to produce a more prolonged period of analgesia. Although pain relief usually is provided by analgesics, there are other important ways to reduce the degree of pain. For example, passing a nasogastric tube (which is an important part of the diagnostic workup of a horse with colic) may remove any fluid that has accumulated in the stomach because of an obstruction of the small intestine. The removal of this fluid not only relieves pain from gastric distention but also prevents rupture of the stomach. Fluid Therapy: Many horses with colic benefit from fluid therapy to ensure that they do not become dehydrated and that the blood supply to the kidneys and other vital organs is not reduced. Horses with strangulating obstruction or enteritis must be given fluids IV because absorption of fluids from the diseased intestine is reduced and fluid may be secreted into the lumen of the intestine. Most of the fluid is reabsorbed from the ingesta in the cecum and colons. In fact, ~95% of the fluid that normally enters the lumen of the large intestine is returned to the bloodstream. Therefore, horses with intestinal obstructions near the pelvic flexure usually require relatively small amounts of IV fluids, whereas horses with small-intestinal obstructions need extremely large amounts. In most instances, however, fluid therapy must be started before laboratory results are available, particularly when the horse is showing clinical signs of circulatory shock. Fluids are sometimes given through the nasogastric tube as part of the treatment of impactions of the colon. The same result can be accomplished by giving the fluids IV because “overhydration” causes the intestine to secrete fluid into impacted feed material. If the horse will not drink voluntarily and there is no obstruction in the small intestine, hydration may be maintained by administering fluids through the tube. Fluids or medications should not be given through the nasogastric tube if fluid reflux is being removed from the stomach. This indicates that either the stomach or the small intestine is not emptying properly. Protection Against Bacterial Endotoxin: Endotoxin, a part of the outer coating of enteric gram-negative bacteria, is released when the bacteria die or multiply rapidly. Normally, endotoxin is restricted to the intestinal lumen, but if the intestinal mucosal lining is damaged due to ischemia, endotoxin moves into the peritoneal cavity or the bloodstream. It then interacts with the mononuclear phagocytes and triggers an inflammatory response that can include fever, depression, hypotension, coagulation abnormalities, and eventually death. Minimizing the inflammatory responses to endotoxemia is a vital part of colic therapy.

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Prostaglandins, inflammatory mediators produced in response to endotoxemia, are involved in causing many of endotoxin's early ill effects. Flunixin meglumine reduces the cellular production of prostaglandins and can help prevent some of their effects. Because flunixin can help protect against endotoxemia at dosages less than the recommended dose (1.1 mg/kg), smaller doses (0.25 mg/kg) can be administered without masking clinical signs associated with conditions that require surgery. There is considerable controversy regarding the efficacy of plasma or serum that contains antibodies designed to neutralize endotoxin. These antibodies are directed against the components of endotoxins that are consistent among different gram-negative bacteria. Because endotoxin itself stimulates the generation of a wide array of inflammatory substances that ultimately produce the pathophysiologic effects, neutralizing antibodies should be used as early in the course of the disease as possible. Intestinal Lubricants and Laxatives: A common cause of colic in horses is simple obstruction of the large intestine by dried ingesta, sometimes mixed with sand. These impactions of the large intestine generally occur near the pelvic flexure or in the right dorsal colon but may involve any portion of the large colon, descending colon, or cecum. In most instances, lubricants or fecal-softening agents given through a nasogastric tube soften the impacted ingesta, allowing it to be passed. This form of therapy can be aided by the simultaneous administration of IV fluids. Mineral oil is the most commonly used medication in the treatment of a large-colon impaction. It coats the inside of the intestine and aids the normal movement of ingesta along the GI tract. It is administered through a nasogastric tube, up to 1 gal. once or twice daily, until the impaction is resolved. Although mineral oil is safe, it is not highly effective in treating severe impactions or sand impactions because it may simply pass by the obstruction without softening it. Dioctyl sodium sulfosuccinate (DSS) is a soap-like compound that acts by drawing water into the dry ingesta. It is more effective than mineral oil in softening impactions; however, it may interfere with the normal fluid absorptive functions of the colon and can be toxic. Thus, DSS can be given safely only in small quantities two times 48 hr apart. A safe and useful compound for treating impactions, especially those containing sand, is psyllium hydrophilic mucilloid. When mixed with water, it forms a gelatinous mass that carries ingesta along the GI tract. Although usually given through a nasogastric tube to horses with impactions, psyllium also may be used as a preventive by mixing the dry powder into the feed. Strong laxatives that stimulate intestinal contractions are not commonly used to treat impactions and, in fact, may worsen the problem. Occasionally, horses with extremely hard impactions are treated with magnesium sulfate, which draws body fluids into the GI tract. Side effects include dehydration and an increased risk of diarrhea. Larvicidal Deworming: The normal migratory routes of the larvae of large bloodworms, particularly Strongylus vulgaris , have been implicated in many cases of colic. In response to the migratory and maturation processes of the larvae in the cranial mesenteric artery, the wall of the artery becomes thickened and forms loose plaques of inflammatory tissue. These plaques activate coagulation, resulting in the formation of a thrombus, which changes the way blood flows in the artery. Thromboembolism may occur and decrease the blood supply to the intestine, which results in an alteration in intestinal motility, a change in the absorption of nutrients from the intestine, or death of the intestine. Thus, thromboembolism can cause recurrent episodes of colic and weight loss. Most deworming medications when given at recommended dosages do not kill migrating S vulgaris larvae. The one exception is ivermectin. Fenbendozole kills migrating strongyles. Surgery: Surgery usually is necessary if there is a mechanical obstruction to the normal flow of ingesta that cannot be corrected medically or if the obstruction also interferes with the intestinal blood supply. Under most circumstances, horses exhibiting signs of severe abdominal pain nonresponsive to analgesic therapy require emergency abdominal surgery. Horses with an abnormally distended intestine on rectal examination and serosanguinous peritoneal fluid with an increased total protein concentration and number of red blood cells probably have a strangulating lesion that requires surgical correction. Some of the more commonly used indications for surgical intervention in horses with colic include uncontrollable pain; >4 L of fluid reflux from the stomach; no borborygmi on auscultation; peritoneal fluid with increased protein, erythrocytes, and toxic neutrophils; and a tightly distended intestine, displaced colon, or enterolith or foreign body identified on rectal examination. Performing colic surgery (if indicated) early is critical to success. Therefore, it is more important to decide if the horse should be referred to a clinic where surgery could be performed if needed, rather than trying to determine if emergency surgery is definitively required. Using this approach, it would be prudent to refer the following types of cases: 1) a horse that responds initially to an analgesic but requires additional analgesic therapy a few hours later, 2) a horse that continues to exhibit signs of pain despite administration of various analgesics, 3) a horse that remains painful but has normal peritoneal fluid, 4) a horse with distended small intestine on rectal examination but lacking fluid reflux, or 5) a horse with large quantities of fluid removed from the stomach but no distended small intestine palpable on rectal examination. Prognosis:
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Survival rates are highest for horses with mild abdominal pain and are lowest for horses with severe pain. Horses with palpable intestinal distention have lower survival rates than horses lacking evidence of intestinal distention, and survival rates are even lower if no intestinal sounds are audible on auscultation of the abdomen. Red mucous membranes are frequently associated with bacterial endotoxemia, which decreases the survival rate. Cardiovascular system function reflects the degree of shock and, therefore, correlates with the prognosis for survival. For instance, horses with low systolic blood pressure or a high heart rate have a decreased chance of survival. Of the laboratory analyses used to predict survival, blood lactate concentration and the anion gap have received the greatest attention. Measurement of blood lactate has been used as an indicator of tissue perfusion, with increasing concentrations of lactic acid corresponding with poor tissue perfusion. Similarly, the anion gap (the calculated difference between the measured cations and the measured anions) reflects the generation of organic anions, most notably lactic acid, due to reduced tissue perfusion. The concentration of protein in the peritoneal fluid also has been used to predict survival, with higher concentrations associated with a poorer prognosis. Proximal Enteritis-jejunitis: The cause is unknown. The affected intestine contains lesions varying from hyperemia to necrosis and infiltration of the submucosa with inflammatory cells. Often, there is edema and hemorrhage in the various layers of the intestinal wall. Inguinal Hernia: Inguinal hernias generally occur in stallions after breeding a mare, trauma, or a hard workout. Hernias appear to be most common in Tennessee Walking Horses, American Saddlebreds, and Standardbreds. In most cases, the hernia produces acute colic. The intestine descends through the vaginal ring in most cases and lies next to the testis and epididymis. Rectal examination will reveal distended loops of small intestine, with one of the loops tracing to the vaginal ring on the affected side. There will be gastric reflux, and the horse's condition will deteriorate rapidly. Peritoneal fluid generally reflects the degree of ischemia. Surgery involves a ventral midline celiotomy and inguinal approach to reduce the hernia. Often, the testicle on the affected side must be removed, and the affected intestine resected. The prognosis for survival seems to be breed-dependent, with Standardbred horses having a good prognosis and Tennessee Walking Horses having a fair to poor prognosis. Presumably, this reflects the fact that many Tennessee Walking Horse stallions with inguinal hernias show little evidence of pain. Enterolithiasis: Enteroliths are concretions composed of magnesium ammonium phosphate crystals around a nidus (eg, wire, stone, nail). Enteroliths may occur singly or in groups and are commonly found in horses in certain parts of California, the southwest, Indiana, and Florida. Enterolithiasis commonly affects horses of the Arabian breed, but the fact that these horses are extremely popular in the aforementioned areas confounds the question regarding breed association. Many horses with enterolithiasis have a history of recurring colic, presumably indicating that the enterolith(s) had caused partial or temporary obstruction of the colonic lumen. If the enterolith becomes lodged at the origin of the transverse colon, the colon proximal to the obstruction distends with gas and the pain is severe. Distention of the abdomen may be marked. Heart and respiratory rates are increased, and the mucous membranes may be pale or pink. Generally, colonic and cecal distention is evident on rectal examination, but the mass rarely is palpable because the transverse colon is cranial to the cranial mesenteric artery. Radiography may be used to identify the enteroliths. Treatment involves surgery via a ventral midline celiotomy to decompress the colon and cecum and then to remove the stone(s). Bloat In Ruminants: Introduction (Ruminal tympany) Bloat is an overdistention of the rumenoreticulum with the gases of fermentation, either in the form of a persistent foam mixed with the ruminal contents—called primary or frothy bloat, or in the form of free-gas separated from the ingesta— called secondary or free-gas bloat. It is predominantly a disorder of cattle but may also occur in sheep. Etiology and Pathogenesis: In primary ruminal tympany, or frothy bloat, the cause is entrapment of the normal gases of fermentation in a stable foam. Coalescence of the small gas bubbles is inhibited, and intraruminal pressure increases because eructation cannot occur. Several factors, both animal and plant, influence the formation of a stable foam. Soluble leaf proteins, saponins, and hemicelluloses are believed to be the primary foaming agents and to form a monomolecular layer around gas rumen bubbles that has its greatest stability at about pH 6.0. Salivary mucin is antifoaming, but saliva production is reduced with succulent forages. Bloat-producing pastures are more rapidly digested and may release a greater amount of small chloroplast particles that trap gas bubbles and prevent their coalescence. Susceptible animals have a higher concentration of small feed particles suspended in the rumen, and the contents contain small yellow bubbles before feeding. The immediate effect of feeding is
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probably to supply nutrients for a burst of microbial fermentation. However, the major factor that determines if bloat will occur is the nature of the ruminal contents. Protein content and rate of digestion reflect the forage's potential for causing bloat. Legume forages such as alfalfa and clover have a higher percentage of protein and are digested more quickly. Other legumes, such as sainfoin and birdsfoot trefoil, are high in protein but do not cause bloat, probably because they contain condensed tannins, which precipitate protein and are digested more slowly than alfalfa or clover. The cause of the foam in feedlot bloat is uncertain but is thought to be either the production of insoluble slime by certain species of rumen bacteria in cattle fed high-carbohydrate diets or the entrapment of the gases of fermentation by the fine particle size of ground feed. In secondary ruminal tympany, or free-gas bloat, physical obstruction of eructation occurs from esophageal obstruction caused by a foreign body, stenosis, or pressure from enlargement outside the esophagus (as from lymphadenopathy). Ruminal tympany also occurs with hypocalcemia. Unusual postures, particularly lateral recumbency, are commonly associated with secondary tympany; ruminants may die of bloat if they become accidentally cast in dorsal recumbency or other restrictive positions in handling facilities, crowded transportation vehicles, or irrigation ditches. Clinical Findings: Bloat is a common cause of sudden death. Cattle not observed closely, such as pastured and feedlot cattle and dry dairy cattle, usually are found dead; in lactating dairy cattle, which are observed regularly, bloat commonly begins within 1 hr after being turned onto a bloat-producing pasture. Bloat may occur on the first day after being placed on the pasture but more commonly occurs on the second or third day. Dyspnea and grunting are marked and are accompanied by mouth breathing, protrusion of the tongue, and extension of the head. Occasionally, vomiting occurs. Rumen motility does not decrease until bloat is severe. If the tympany continues to worsen, the animal will collapse and die. Death may occur within 1 hr after grazing began but is more common ~3-4 hr after onset of clinical signs. In a group of affected cattle, there are usually several with clinical bloat and some with mild to moderate abdominal distention. In secondary bloat, the excess gas is usually free on top of the solid and fluid ruminal contents, although frothy bloat may occur in vagal indigestion when there is increased ruminal activity. In free-gas bloat, the passage of a stomach tube or trocarization releases large quantities of gas and alleviates distention. Treatment: In life-threatening cases, an emergency rumenotomy may be necessary; it is accompanied by an explosive release of ruminal contents and, thus, marked relief for the cow. A trocar and cannula may be used for emergency relief, although the standard-sized instrument is not large enough to allow the viscous, stable foam in peracute cases to escape quickly enough. If the cannula provides some relief, the antifoaming agent of choice can be administered through the cannula, which can remain in place until the animal has returned to normal, usually within several hours. When the animal's life is not immediately threatened, passing a stomach tube of the largest bore possible is recommended. In frothy bloat, it may be impossible to reduce the pressure with the tube, and an antifoaming agent should be administered while the tube is in place. A variety of antifoaming agents are effective, including vegetable oils (eg, peanut, corn, soybean) and mineral oils (paraffins), at doses of 80-250 mL. Dioctyl sodium sulfosuccinate, a surfactant, is commonly incorporated into one of the above oils and sold as proprietary antibloat remedies, which are effective if administered early. Control and Prevention: Prevention of pasture bloat can be difficult. For hay to be effective, it must be at least one-third of the diet. The only satisfactory method available to prevent pasture bloating is strategic administration of an antifoaming agent. Available antifoaming agents include oils and fats and synthetic nonionic surfactants. Oils and fats are given at 2-4 oz (60-120 mL)/head/day; doses up to 8 oz (240 mL) are indicated during most dangerous periods. Poloxalene, a synthetic polymer, is a highly effective nonionic surfactant given at 10-20 g/head/day and up to 40 g in high-risk situations. It is safe and economical to use and is administered daily through the susceptible period by adding to water, feed grain mixtures, or molasses. Alcohol ethoxylate detergents are equally effective and are more palatable than poloxalene. Ionophores are effective in preventing bloat, and a sustained-release capsule that is administered into the rumen and releases 300 mg of monensin daily for a 100-day period protects against pasture bloat and improves milk production on bloat-prone pastures. Grain Overload: Introduction Lactic acidosis, Carbohydrate engorgement, Rumen impaction) Grain overload is an acute disease of ruminants characterized by indigestion, rumen stasis, dehydration, acidosis, toxemia, incoordination, collapse, and frequently death. Etiology and Pathogenesis:
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The disease is most common in cattle that accidentally gain access to large quantities of readily digestible carbohydrates, particularly grain. The number of gram-positive bacteria ( Streptococcus bovis ) increases markedly, which results in the production of large quantities of lactic acid. The rumen pH falls to ≤5, which destroys protozoa, cellulolytic organisms, and lactateutilizing organisms, and impairs rumen motility. The low pH allows the lactobacilli to utilize the carbohydrate and to produce excessive quantities of lactic acid. The superimposition of lactic acid and its salt, lactate, on the existing solutes in the rumen liquid causes osmotic pressure to rise substantially, which results in the movement of excessive quantities of fluid into the rumen, which causes dehydration. The lactic acid causes a chemical rumenitis, and its absorption results in lactic acidosis. In addition to acidosis and dehydration, the pathophysiologic consequences are hemoconcentration, cardiovascular collapse, renal failure, muscular weakness, shock, and death. Animals that survive may develop mycotic rumenitis in several days, hepatic necrobacillosis several weeks or months later, or chronic laminitis, as well as evidence of ruminal scars at slaughter. Clinical Findings: Within 24-48 hr of the onset of severe overload, some animals will be recumbent, some will be staggering, and others will be standing quietly; all will be completely off feed. The heart rate usually is increased in accordance with severity of the acidosis; prognosis is poor for cattle with rates of 120-140/min. Diarrhea is common and usually profuse; the feces are soft to liquid, yellow or tan, and have an obvious sweet-sour odor. The feces frequently contain undigested kernels of the feed that has induced the overload. In mild cases, dehydration equals 4-6% body wt; in severe cases, up to 10-12%. They commonly lie quietly, often with the head turned into the flank, and their response to any stimulus is much decreased so that they resemble cases of parturient paresis ( Parturient Paresis In Cows: Introduction). Acute laminitis may be present and is most common in those animals that are not severely affected; chronic laminitis may occur weeks or months later. Anuria is a common finding in acute cases, and diuresis after fluid therapy is a good prognostic sign. Death may occur in 24-72 hr, and rapid development of acute signs, particularly recumbency, indicates an urgent need for radical treatment. Diagnosis: Although parturient paresis ( Parturient Paresis In Cows: Introduction) may resemble rumen overload, diarrhea and dehydration are not typical, the intensity of heart sounds is reduced, and the response to calcium injection is usually dramatic. Peracute coliform mastitis and acute diffuse peritonitis may also resemble overload, but usually a careful examination will reveal the cause of the toxemia. To avoid an increase in pH on exposure to air, rumen fluid obtained by stomach tube or paracentesis should be checked promptly. Normally, the pH in cattle on roughage is 6-7, in those on a grain diet, 5.5-6. Values below those ranges are strongly suggestive of overload, and a pH <5 indicates severe acidosis. Wide-range (2-11) pH indicator paper is suitable for field use. Ruminal fluid may be examined microscopically; 5-7 protozoa are normally seen under low power; in acidosis, the protozoa are virtually absent. A Gram's stain of the fluid will reveal a change from predominantly gram-negative bacteria (normal) to predominantly gram-positive bacteria in acidosis. Cattle found while engorging or shortly thereafter should be allowed no more concentrate or water, but plenty of good hay for up to 24 hr, and forced to exercise periodically. Treatment: For all cattle suspected of having eaten large quantities of concentrate, it is important to restrict water intake for the first 18-24 hr. If overload is serious, slaughter should be considered; in feeders nearing the end of their feeding period, it may well be the most economical choice. In less severe cases, emptying the rumen is unnecessary. Traumatic Reticuloperitonitis: Introduction (Hardware disease, Traumatic gastritis) Cattle commonly ingest foreign objects because they do not discriminate against hard materials in feed and do not completely masticate feed before swallowing. Clinical Findings: The initial attack is characterized by sudden onset of ruminoreticular atony and a sharp fall in milk production. Fecal output is decreased. Initially, the cow exhibits an arched back; an anxious expression; a reluctance to move; and an uneasy, careful gait. Forced sudden movements as well as defecating, urinating, lying down, getting up, and stepping over barriers may be accompanied by groaning. A grunt may be elicited by applying pressure to the xiphoid or by elevating this area firmly and then pinching the chine, which causes extension of the thorax and lower abdomen. The grunt can be detected by placing a stethoscope over the trachea. Some cattle develop chronic vagal indigestion, possibly due to the adhesions that form after foreign body perforation, particularly those on the ventromedial reticulum.
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Cows with pleuritis or pericarditis due to foreign body perforation usually are depressed, tachycardic (>90 beats/min), and pyrexic (104°F [40°C]). Thoracentesis may yield several liters of fluid. Traumatic pericarditis usually is characterized by muffled heart sounds; possibly with pericardial friction rubs, and occasionally by gas and fluid splashing sounds on auscultation. This has been described as a washing machine murmur. Jugular vein distention with a pronounced jugular pulse is present early in the course, and congestive heart failure with marked submandibular and brisket edema is a frequent sequela. Prognosis is grave with these complications. Penetration through the myocardium usually produces extensive hemorrhage into the pericardial sac and sudden death. Diagnosis: Without an accurate history and when the condition has been present for several days or longer, diagnosis is more difficult. Other causes of peritonitis, particularly perforated abomasal ulcers, can be difficult to distinguish from traumatic reticuloperitonitis. Differential diagnoses should include conditions that can produce variable or nonspecific GI signs, eg, indigestion, lymphosarcoma, or intestinal obstruction. Abomasal displacement or volvulus should be ruled out by simultaneous auscultation and percussion. Pleuritis or pericarditis of nontraumatic origin produces signs similar to those associated with foreign body perforation. Although not always necessary, laboratory tests may be helpful. In many cases, there is an increase in neutrophils with a left shift. Fibrinogen and, in chronic cases, total plasma protein concentrations may be high. The acid-base status and serum electrolyte levels are typically because abomasal and small-intestinal absorption can remain normal. However, marked hypokalemic, hypochloremic metabolic alkalosis can occur, presumably because adynamic ileus from peritonitis can affect abomasal and GI motility and resorption of abomasal secretions. The metabolic alkalosis can be created or exacerbated by treatment with alkalinizing agents such as magnesium hydroxide used as a laxative. Radiographs may detect metallic material in the reticulum. Electronic metal detectors will identify metal in the reticulum but do not distinguish between perforating and nonperforating foreign bodies. Treatment: Treatment of the typical case seen early in its course may be surgical or medical. Surgery involves rumenotomy with manual removal of the object or objects; if an abscess is adhered to the reticulum, it should be aspirated (to confirm that it is an abscess) and then drained into the reticulum. Because of the mixed bacterial flora in the lesion, a broad-spectrum antimicrobial agent such as oxytetracycline (6.6-11 mg/kg) should be used. Prevention: Preventive measures include avoiding the use of baling wire, passing feed over magnets to remove metallic objects, keeping cattle away from sites of new construction, and completely removing old buildings and fences. Additionally, bar magnets may be administered PO, preferably after fasting for 18-24 hr. Usually, the magnet remains in the reticulum and holds any ferromagnetic objects on its surface. There is good evidence that giving magnets to all herd replacement heifers and bulls at ~1 yr of age minimizes incidence of traumatic reticuloperitonitis. Esophageal Obstruction (choke): Overview Esophageal obstruction or choke, in which the esophagus is obstructed by food masses or foreign objects, is by far the most common esophageal disease in large animals. Horses most frequently obstruct on greedily eaten dried grains or hay. Cattle more usually obstruct on a single solid object, eg, apples, beets, potatoes, turnips, or corn stalks or ears of corn. Clinical Findings: In horses, the classic clinical findings associated with esophageal obstruction are overflow of esophageal food and regurgitation of that food down the nostrils. Nasal discharge of saliva and food material, which usually also spills from the pharynx into the airway, induces coughing. The horse is anxious and may stretch and arch its neck but yet may still attempt to continue to either eat or drink. In cattle, acute and complete esophageal obstruction is an emergency because it prohibits the eructation of ruminal gases, and free-gas bloat develops. This in turn may result in asphyxia as the expanding rumen puts pressure on the diaphragm and reduces return of blood to the heart. The cow may be bloated and in distress or recumbent, or there may be protrusion of the tongue, extension of the head, and grinding of the teeth with excess salivation. Diagnosis: Palpation of the esophagus may locate cervically lodged objects. It is important that each case be carefully evaluated independently because, in many instances, the complications of esophageal diseases (eg, aspiration pneumonia) may prohibit or limit the effectiveness of treatment. In such cases, thoracic radiography, hematology, and biochemical serum analyses are indicated. Treatment: In horses, many cases of obstruction caused by greedily eaten grain or hay may resolve spontaneously. The horse should be held off feed and water, and mild sedation and smooth muscle relaxants may be effective. (It is interesting to note that compounds such as acepromazine have some effect in these cases, even though the esophagus has striated muscle, ie, special visceral muscle.) Horses should be monitored because spontaneous resolution may take from a few hours to several
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days. However, the longer the horse is obstructed, the greater the danger of pressure necrosis or esophagitis and complications of aspiration pneumonia. A nasogastric tube should be placed before general anesthesia is induced; a cuffed endotracheal tube must be used to protect the airway. Repeated pumping and siphoning of warm water usually loosens the impacted food material. Oral food should be introduced gradually. In cattle, esophageal obstruction accompanied by ruminal tympany is an emergency, and the bloat ( Bloat In Ruminants: Introduction) must be relieved by trocarization through the left sublumbar foci. Once the tympany has been relieved, then solid objects (eg, potatoes) may often, as in horses, be massaged or spontaneously dislodge as their outer surfaces are softened by saliva. Complications of Esophageal Obstruction In both horses and cattle, inhalation pneumonia and resultant fulminating septic pleural pneumonia may be complications of esophageal obstruction. Esophageal Obstruction Secondary to Extraesophageal Disease Cervical and prethoracic trauma may result in scar formation that may lead to constriction of the esophagus. Esophageal Strictures Idiopathic esophageal strictures occur in foals. Critical cases should be referred to advanced surgical centers, and esophagomyotomy or esophageal resection and anastomosis may be attempted. Ascaris sp Adults of the large roundworm, Ascaris suum , are found principally in the small intestine but may migrate into the stomach or bile ducts. When the eggs are ingested, the larvae hatch in the intestine, penetrate the intestinal wall, and enter the portal circulation. After a period in the liver, they are carried by the circulation to the lungs, where they pass through the capillaries into the alveolar spaces. About 9-10 days after ingestion, the larvae pass up the bronchial tree, return to the GI tract, and then mature in the small intestine. The first eggs are passed 2-2½ mo after infection. Clinical Findings: Adult worms may significantly reduce the growth rate of young pigs; if sufficiently numerous, they may cause mechanical obstruction of the intestine, or migrate into and occlude the bile ducts, producing icterus. Migration of larvae through the liver causes hemorrhage and fibrosis that appears as “white spots” under the capsule. In heavy infections, the larvae can cause pulmonary edema and consolidation as well as exacerbate swine influenza and endemic pneumonia. Affected pigs show abdominal breathing, commonly referred to as “thumps.” In addition to the respiratory signs, marked unthriftiness and weight loss are seen. Permanent stunting may result in pigs up to 4-5 mo old. Diagnosis: During the patent period, diagnosis can be made by demonstrating the typical eggs in the feces. Treatment: Many drugs have been used to remove adult ascarids. Piperazine preparations have low toxicity and are moderately priced. The benzimidazoles and probenzimidazoles, dichlorvos, ivermectin, levamisole, and pyrantel are effective and have a broader spectrum of activity than piperazine. Gastrointestinal Ulcersin Large Animals: Introduction Gastric ulcers are important in adult horses, foals, and pigs. Abomasal ulcers ( Abomasal Ulcers) in mature cattle and calves appear to be increasing in importance. The prevalence of gastric ulcers in horses is ~50% in foals, almost 100% in some groups of weanlings and yearlings, and up to 88% in Thoroughbreds. Gastroduodenal Ulcers in Horses Etiology: The etiology of equine gastric ulcers is poorly understood and is likely multifactorial. Commonly used nonsteroidal anti-inflammatory drugs (eg, phenylbutazone, flunixin meglumine, and ketoprofen) have caused gastric ulceration in horses. Diets high in concentrates and low in roughage may also play a role. Clinical Findings: Most gastric ulcers in foals and adult horses are apparently asymptomatic. Symptomatic foals may show abdominal pain, bruxism, interrupted nursing, dorsal recumbency, and ptyalism. Most foals with signs of pain have lesions in the glandular mucosa or duodenum. Diagnosis: Endoscopy is the most accurate means of diagnosis in foals and adult horses.
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Treatment: The histamine H2-receptor antagonists cimetidine and ranitidine are reportedly effective in treating foals and adult horses but, because of a short duration of action, must be administered 3-4 times daily. Omeprazole, a proton pump inhibitor, causes a prolonged (24 hr) inhibition of gastric acid production and enhances healing of gastric ulcers in horses. Omeprazole can be administered once daily. Antacids appear to relieve clinical signs but must be administered frequently and are unlikely to enhance healing. Currently, omeprazole is the only compound approved by the FDA for treatment of gastroduodenal ulcers in horses. Gastric Ulcers in Pigs Etiology: The cause is unknown. Ulcers occur in pigs of all ages but are most common in confined growing pigs (100-200 lb [4590 kg]) fed pelleted feed or finely ground rations that may be deficient in vitamin E or selenium, and also in pigs fed large quantities of skimmed milk or whey. Fungi may play a role, especially if the diet is high in sugar. Also, the stress of confinement rearing is thought to promote hyperacidity, which may contribute to ulcer development. Clinical Findings: In the acute form, hemorrhage results in anorexia, weakness, anemia, and black, tarry feces; death can occur in hours or days. In the chronic form, unthriftiness, anemia, and black, tarry feces are characteristic; the pig may survive for several weeks. Pigs with the subclinical form may not reach maturity at the expected time; in these pigs, the ulcer usually heals and a scar remains. Lesions: The typical terminal lesion is found in the gastric mucosa near the esophageal opening in a rectangular area of white, glistening, nonglandular, squamous epithelium. Diagnosis and Treatment: Appearance in a pen of one or two listless, anorectic pigs that show weight loss, anemia, dark feces, and sometimes dyspnea is suggestive of gastric ulceration, as is the sudden death of an apparently healthy pig. Cimetidine (300 mg/pig, b.i.d.) has been used with some success in treating gastric ulcers in growing pigs, but its use may not be economically feasible. Controlling chronic respiratory disease is important. Feeding meal rather than pellets with a particle size recommended at 600-700 µm in diameter will be of value but may have a negative effect on feed conversion. Hepatic Disease In Large Animals: Introduction Hepatic disease occurs frequently in large animals, especially horses. Increases in serum hepatic enzymes and total bile acid concentration may indicate hepatic dysfunction, insult, disease, or failure. In horses, diseases that frequently result in hepatic failure include Theiler's disease, Tyzzer's disease, pyrrolizidine alkaloid toxicosis, hepatic lipidosis, suppurative cholangitis, cholelithiasis, chronic active hepatitis, and ferrous fumarate toxicosis. Diseases that sporadically result in hepatic failure include obstructive biliary disease associated with intestinal displacement, aflatoxicosis, leukoencephalomalacia, pancreatic disease, duodenal ulcerations, kleingrass or Alsike clover poisoning, portal caval shunts, hepatic abscess, hepatic neoplasia, and perinatal herpesvirus 1 infections. Less frequently, hepatic failure is associated with endotoxemia, steroid administration, inhalant anesthesia, systemic granulomatous disease, drug-induced amyloidosis, or parasite damage. In ruminants, hepatobiliary disease is associated with hepatic lipidosis, hepatic abscesses, endotoxemia, pyrrolizidine alkaloid and other plant toxicities, certain clostridial diseases, liver flukes, mycotoxicosis, and mineral toxicity (copper, iron, zinc) or deficiency (cobalt). Vitamin E or selenium deficiency (hepatosis dietetica), aflatoxicosis, ascarid migration, bacterial hepatitis, and ingestion of toxic substances (eg, coal tar, cyanamide, blue-green algae, plants, gossypol) are associated with hepatic injury in swine. Prognosis for animals with liver failure is usually unfavorable. Clinical Findings: Clinical signs of hepatic disease may not be evident until >60-80% of the liver parenchyma is nonfunctional or when hepatic dysfunction is secondary to disease in another organ system. Icterus, weight loss, or abnormal behavior are common in horses with liver failure. Weight loss is a common clinical sign in chronic liver disease and may be the only sign associated with liver abscesses. Fasting hyperbilirubinemia is a more common cause of icterus in horses and is not associated with hepatic disease. In ruminants, icterus is more commonly due to hemolytic anemia and primarily involves increases in indirect bilirubin. Hyperbilirubinemia caused by obstructive biliary conditions is rare in goats. Signs of hepatic encephalopathy range from nonspecific depression and lethargy to head-pressing, circling, aimless walking, dysphagia, ataxia, persistent yawning, or aggressiveness. Pharyngeal or laryngeal collapse with loud, stertorous inspiratory noises and dyspnea occurs in some cases of hepatic failure, especially in ponies. The pathogenesis of hepatic encephalopathy is unknown, but proposed theories include ammonia as a neurotoxin, alterations in monoamine neurotransmission (serotonin, tryptophan) or catecholamine neurotransmitters, imbalance between amino acid neurotransmitters (γ-aminobutyric acid, glutamate) and increased cerebral levels of endogenous benzodiazepine-like
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substances. Although the signs can be dramatic, hepatic encephalopathy is potentially reversible if the underlying hepatic disease is resolved. Photosensitization, which occurs with acute or chronic liver failure, must be differentiated from primary photosensitization. Hepatogenous photosensitization occurs when compromised hepatic function results in phylloerythrin, a photodynamic metabolite of chlorophyll, entering the skin. Phylloerythrin in the skin reacts with ultraviolet light and releases energy, causing inflammation and skin damage. Signs of photosensitization are varied but include uneasiness, pain, pruritus, severe dermatitis with erythema, extensive subcutaneous edema, skin ulceration, sloughing of skin and ophthalmia with lacrimation, photophobia, and corneal cloudiness. Dermatitis and edema are particularly evident on nonpigmented, light-colored or hairless areas of the body and areas exposed to sun. Areas of mucocutaneous junctions and patches of white hair are the most common sites of photosensitization in cattle. Blindness, pyoderma, loss of condition, and occasionally death are possible sequelae. Pruritus may result from photosensitization or from deposition of bile salts in the skin secondary to alterations in hepatic excretion. Diarrhea or constipation may be seen in animals with hepatic disease. Diarrhea is more commonly seen in cattle than in horses with chronic liver disease. Recurrent colic, intermittent fever, icterus, weight loss, and hepatic encephalopathy may be seen in horses with choleliths that obstruct the common bile duct. Hypoalbuminemia and hypoproteinemia most commonly occur with chronic liver disease. Generalized ascites or dependent edema may result. Ascites is related to portal hypertension caused by venous blockage and increased hydrostatic pressure and to protein leakage into the peritoneal cavity. The abdominal fluid present with liver disease usually is a modified transudate. Hypoalbuminemia can aggravate the ascites, but if it occurs alone, it more likely will cause intermandibular, brisket, or ventral edema. Clinical signs of severe or terminal hepatic failure include coagulopathies and hemorrhage due to lack of clotting factors produced by the liver (II, V, IX, and X). A prolonged prothrombin time is usually seen first because factor VII has the shortest plasma half-life. In young ruminants and animals with a simple digestive tract, cholestasis may result in lighter color feces being passed due to loss of stercobilin, a metabolite of bilirubin. Liver disease should always be considered when nonspecific clinical signs, such as depression, weight loss, intermittent fever, and recurrent colic, are present without an apparent cause. Laboratory Analyses: Routine biochemical tests such as serum enzyme concentrations are sensitive indicators of liver disease, but they do not assess hepatic function. Serum Enzyme Concentrations: Serum concentrations of liver-specific enzymes are generally higher in acute liver disease than in chronic liver disease. Sequential measurements of serum gamma glutamyltransferase (GGT), sorbitol dehydrogenase (SDH), AST, bilirubin, and bile acids are commonly used to assess hepatic dysfunction and disease in large animals. Serum GGT, bilirubin and total bile acid concentrations, and sulfobremophthalein (BSP®) clearance are not sensitive indicators of liver disease in young calves. Although GGT may be present in the pancreas, kidney, and udder, as well as in the canalicular surfaces of hepatocytes and bile duct epithelium, it is the single test of highest sensitivity for liver disease in adult large animals. Chronic hepatic fibrosis is the only liver disease in which an abnormal increase in GGT may not be seen. Increase of GGT is most pronounced with obstructive biliary disease. In acute hepatic disease in horses, GGT may continue to increase for 714 days despite clinical improvement and return toward normal of other laboratory tests. Neonatal foals and young horses, especially those in training, may show a nonspecific increase in GGT that is not associated with liver disease or other increases in liver enzymes or serum bile acid concentration. GGT is of little value in diagnosing liver disease in neonatal calves or lambs because it is present in colostrum and milk. GGT activity may also be increased with colonic displacement or administration of drugs (eg, corticosteroids, rifampin, benzimidazole, anthelmintics). Other liver-derived enzymes are higher in young calves and foals because they come from sources other than the liver. SDH, arginase, ornithine carbamoyltransferase (OCT), AST, isoenzyme 5 lactate dehydrogenase (LDH-5), glutamate dehydrogenase (GLDH), and alkaline phosphatase (AP) are also used to assess hepatic dysfunction and disease. Arginase, SDH, and OCT are liver-specific enzymes in horses, most ruminants, and swine. SDH is most predictive for active hepatocellular disease. SDH can also be increased in obstructive GI lesions, endotoxemia, anoxia from shock, acute anemia, and anesthesia. SDH and LDH-5 usually return to near-normal values 4 days after liver insult and can be used to monitor improvement in hepatic disease. The dehydrogenases, because of their short half-lives, are often not increased in chronic liver disease. AST is highly sensitive for liver disease but lacks specificity because it comes from both liver and muscle. When creatine kinase is simultaneously measured to rule out muscle disease and the serum is not hemolyzed, increases in AST and LDH-5 are caused by hepatocellular disease. AST remains increased 7-10 days after an acute transient insult to the liver. SDH and AST may be markedly increased with intrahepatic cholestasis and mildly increased with extrahepatic cholestasis. Increases in AP and GGT are associated with irritation or destruction of biliary epithelium and biliary obstruction. AP comes from the placenta, bone, macrophages, intestinal epithelium, and liver. In very young calves and
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foals, AP is increased probably because of the placental or bone source. In young calves, AP levels up to 1,000 IU/L at birth and 500 IU/L at several weeks of age should be considered normal. In calves, AST and GLDH may be the most sensitive of the enzymes for hepatic injury, but AST is increased with many diseases. Serum Total Bile Acid Concentration: Serum total bile acid concentration is increased with hepatic necrosis or cholestasis. Concentrations >20 µmol/L have a high sensitivity and positive productive value for determining liver disease in horses but not in ruminants. Serum total bile acid concentration in most normal horses is <10 µmol/L. Total bile acid concentration remains increased in horses with chronic liver disease. In horses, there is no diurnal variation, no postprandial rise, and no significant hour to hour variation in bile acid concentrations. In cattle, there is a significant hour to hour variation. Total bile acid concentration in recently freshened cows is significantly higher than in cows in midlactation or in 6-mo-old heifers. Total bile acid concentration may be the best single test for hepatic disease in young calves. Serum Bile Pigments: Evaluation of serum bilirubin (direct and indirect) concentration is useful for determining hepatic dysfunction in horses and ruminants. Increases in bilirubin result from hemolysis, hepatocellular disease, cholestasis, or physiologic causes. Horses with anorexia may have a physiologic increase in total serum bilirubin as high as 10.5 mg/dL, with >90% of this being measured as indirect bilirubin. A physiologic hyperbilirubinemia is seen in horses. In foals, indirect and direct bilirubin may be increased significantly with neonatal isoerythrolysis, septicemia, or a portocaval shunt. Enteritis, umbilical infection, or intestinal obstruction may also cause hyperbilirubinemia. Icterus and hyperbilirubinemia in neonatal calves and foals may result from a normal physiologic condition involving breakdown of fetal erythrocytes and from inefficiency in bilirubin excretion. With liver damage in horses or ruminants, most of the retained bilirubin is indirect (unconjugated), and the direct-tototal ratio usually is <0.3. In biliary obstruction, total bilirubin concentrations are increased, with the percentage of direct bilirubin often being ≥25%. With bile blockage or intrahepatic cholestasis, the direct-to-total ratio may be >0.3 in horses or 0.5 in cows. However, adult cattle and calves may have severe liver disease without any increase in serum bilirubin. In cattle, goats, and sheep, circulating bilirubin levels increase only modestly in the face of severe, generalized hepatic disease. Urobilinogen: Increased levels of urobilinogen in urine without hemolysis is suggestive of a hepatic disorder. With complete biliary blockage, there is no urobilinogen in urine. However, the correlation between urobilinogen and hepatocellular disease in animals is poor. Urobilinogen is not very stable in the urine. Serum and Plasma Proteins: Serum albumin and protein concentrations are variable in horses and cattle with hepatic disease. Hypoproteinemia is not common in horses with acute liver disease. Serum albumin is most likely to be reduced in chronic liver disease, likely associated with decreased functional hepatic parenchyma. Hyperproteinemia due to hyperglobulinemia is relatively common in horses with severe acute or chronic liver disease. Plasma fibrinogen concentrations may not be a sensitive test in horses with hepatic insufficiency. Low fibrinogen concentrations may result from parenchymal insufficiency or disseminated intravascular coagulopathy. A high fibrinogen concentration is associated with an inflammatory response in horses with cholangiohepatitis. Prothrombin Time: Serum prothrombin time (PT) is rapidly prolonged with hepatic failure and may be one of the first function tests to return to normal with recovery from acute hepatic disease. Prolonged PT times are common because of poor absorption of vitamin K from the GI tract. Urea, Glucose, and Ammonia: Serum concentration of urea may be decreased in both acute and chronic liver failure. Plasma triglyceride concentrations are markedly increased in ponies, miniature horses, donkeys, and adult horses with hepatic lipidosis. Plasma ammonia levels may be increased but do not correlate well with severity of hepatic encephalopathy except during portocaval shunts. Ingestion of urea or ammonium salts may cause increases of blood ammonia and encephalopathy in horses and cattle. Liver Biopsy: Percutaneous liver biopsy is the definitive means of diagnosing hepatic disease. Liver biopsy may not be advised in an animal with a hepatic abscess because contamination of the peritoneal cavity may result. Treatment and Management: Therapy is most successful when intervention is early, hepatic fibrosis is minimal, and there is evidence of regeneration in the liver. The goals for treatment of large animals with hepatic disease are to control hepatic encephalopathy, to provide supportive care (allowing time for liver regeneration), to treat the underlying disease process and, most importantly, to prevent injury to the animal and persons working with the animal. Animals with hepatic encephalopathy often show aggressive, maniacal, and unpredictable behavior that can result in injury to self or handlers. Hepatic Encephalopathy:

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Because most sedatives and tranquilizers are metabolized by the liver, their elimination half-life may be prolonged in animals with hepatic failure; therefore, dosages should be minimized. Diazepam should be avoided in animals with hepatic encephalopathy because it may enhance the effect of γ-aminobutyric acid on inhibitory neurons and worsen the neurologic signs. Acepromazine should also be avoided because it may lower the seizure threshold. Supplement is added if the animal is hypokalemic or hypophagic. Because rapid correction of the acidosis may exacerbate the neurologic signs, acidosis should be corrected gradually by IV administration of strong ion electrolyte fluids. Therapies directed toward decreasing either ammonia production in and absorption from the bowel include administration of mineral oil, neomycin, lactulose, and metronidazole. Administration of mineral oil decreases absorption and facilitates removal of ammonia. Passing a nasogastric tube in an animal with hepatic encephalopathy must be done cautiously because nasal bleeding may be difficult to control due to decreased clotting factors. In addition, blood swallowed may exacerbate the neurologic signs. Oral administration of neomycin (20-30 mg/kg, q.i.d. for 1 day, or 5.0 mg/kg, t.i.d. for 2 days) decreases ammonia-producing bacteria. Lactulose (0.2 mL/kg, b.i.d., 0.3 mL/kg, q.i.d., PO; or 90-120 mL every 6-8 hr per 450-kg horse) decreases colonic pH and intestinal concentration of ammonia. Metronidazole (10-15 mg/kg, PO, t.i.d.) decreases ammonia-producing organisms in horses but not in food animals. Oral drugs can be mixed with Karo syrup or molasses and given via dose syringe to avoid trauma and risk of passing a nasogastric tube. Neomycin, lactulose and metronidazole may all potentially induce mild to severe diarrhea. Use of the drugs in combination is more likely to induce diarrhea than any one of the drugs given alone. A trimethoprim-sulfa combination is a good empirical choice because of its activity against gram-negative bacteria and its high concentration in bile. Penicillin in combination with an aminoglycoside has a broad spectrum of action and may be of benefit if a Streptococcus sp or an anaerobic or gram-negative coliform is suspected. Pain may be controlled with low doses of nonsteroidal anti-inflammatory drugs (eg, flunixin meglumine, 0.5 mg/kg, IV or IM). Alternatively, in foals, butorphanol (0.07 mg/kg, IM) may be given. Dietary Management: The diet should be fed frequently in relatively small amounts. It should meet dietary energy needs, meet but not greatly exceed dietary protein needs, have a high ratio of branched-chain amino acids to aromatic amino acids, be low in (or at least not contain added) fat or salt, and be high in starch to decrease need for hepatic glucose synthesis. Feeds used successfully in horses include grass or oat hay, corn, and sorghum. Large amounts of molasses may make the feed less palatable and can induce diarrhea. Linseed meal and soybean meal have an excellent branched-chain to aromatic amino acid ratio and may be used as a protein supplement in small quantities. Choke may be a problem in some animals eating beet pulp. Alfalfa hay generally has a better branched-chain to aromatic amino acid ratio than does mature grass hay, but it also has a higher protein content. If plasma ammonia concentration is increased or signs of hepatic encephalopathy are present, lower protein grass forages should be fed. Supplement of vitamins A, D, and B1 and folic acid, possibly with vitamins C and E might be indicated. Vitamin K1 may be indicated in animals with a coagulopathy.

Acute Hepatitis: Overview Infectious, toxic, and undefined etiologies may cause acute hepatitis. Clinical signs may appear suddenly with horses appearing depressed, anorectic, and icteric. Photosensitization, diarrhea, and clotting abnormalities, indicated by excessive bleeding also may occur. Increases in serum SDH and AST activities indicate acute hepatocellular injury. GGT is increased with cholestasis secondary to hepatocyte swelling. Cholestasis results in hyperbilirubinemia, with the direct (conjugated) fraction ranging from 15 to 40% of total in horses. Idiopathic Acute Hepatic Disease (IAHD) (Theiler's disease, Serum hepatitis, Postvaccinal hepatitis, Acute hepatic atrophy) IAHD is the most common cause of acute hepatitis in horses. Etiology and Epidemiology: Many horses with IAHD show clinical signs of hepatic failure 4-10 wk after receiving an equine origin biologic, such as tetanus antitoxin (TAT). In some cases, the affected horse may not have received TAT but may have been in contact with another horse than had received TAT. Others affected have no prior history of exposure to such a product. Subclinical IAHD can also develop after administration of TAT. A Type III (immune-complex mediated) hypersensitivity reaction also has been proposed. Clinical Findings: Horses with IAHD typically present with anorexia, hepatic encephalopathy, and icterus. Serum levels of GGT, AST, and SDH are generally increased, most often in the range of 100-300 IU/L. GGT is frequently further increased during the first few days of illness, despite clinical improvement and eventual recovery in an affected horse. Horses with AST values >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.
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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
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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
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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:
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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 <60% of affected horses. Severity of clinical signs varies considerably, but in the absence of treatment, the mortality rate varies from 5 to 30%, with death occurring from toxemia. Other horses may be euthanized because of laminitis. Diagnosis: A diagnosis can be made based on clinical signs, a transient leukopenia early in clinical disease, and results of paired serum titers for E risticii measured by IFA. Definitive diagnosis requires isolation of E risticii . The IFA test is the most common test for presence of E risticii antibody. Definitive diagnosis at the time of clinical signs is not currently possible, so an antimicrobial specifically aimed at E risticii should be selected. Oxytetracycline is the drug of choice and is given at 6.6 mg/kg, IV, s.i.d. If the horse has E risticii infection, rectal temperature decreases, followed by improvement in attitude, feed intake, and GI sounds within 12 hr of treatment. Because the response to oxytetracycline is so dramatic, it can be used as further confirmation of the diagnosis. Generally, treatment with oxytetracycline is for no more than 5 days. If no improvement is seen within 24 hr of the initial treatment with oxytetracycline, the diagnosis and choice of antimicrobial should be reconsidered. Treatment should also include aggressive IV fluid and electrolyte replacement. Severely affected horses with secondary bacterial colitis and signs of endotoxemia may benefit from treatment with flunixin meglumine and equine plasma containing antibodies against endotoxin. Prevention: Prevention by vaccination is a logical approach, and several inactivated, partially purified, whole-cell vaccines are approved. Duration of immunity from vaccination is shorter than that from natural exposure. In endemic areas, horses should be immunized in the spring, 1 mo before the first cases usually occur and again 4 mo later if cases are still occurring. Vaccination of horses that have had naturally occurring disease probably is not necessary for 2 yr. Vaccination does not guarantee protection from disease. Because definitive diagnosis of Potamac horse fever is difficult, and because it can occur concurrently with salmonellosis, affected horses should be isolated despite the lack of direct transmission of E risticii . Diarrheal Disease in Foals Foal Heat Diarrhea: From 4 to 14 days postnatally, foals often develop a mild, self-limiting diarrhea. During this time, the dam is usually undergoing her first estrous cycle, hence the name “foal heat diarrhea.” Although the cause is unknown, it may be associated with alterations in the foal's intestinal microbial flora or alteration in diet (the foal begins to eat small amounts of hay and grain). The foal remains active and alert and has a normal appetite. Vital signs remain normal. Feces are semiformed to watery and not malodorous. Monitoring is important to ensure the foal's condition does not deteriorate. Specific treatment is usually not necessary, but application of a protectant to the skin around the perineum helps prevent scalding of the buttocks. Bacterial Diarrhea in Foals: Bacterial enterocolitis in neonatal foals can be a component of neonatal septicemia. Organisms that may be involved in diarrhea in neonatal foals include Salmonella spp , Escherichia coli , Klebsiella spp , and Clostridium spp . Intensive antimicrobial therapy, fluid and electrolyte correction, and nursing care are needed. Foals should be evaluated to determine if adequate passive transfer of antibodies has occurred; if not, a plasma transfusion is indicated. (See also septicemia in foals. An acute, fulminant, hemorrhagic diarrhea syndrome with high mortality in young foals <3 days old has been associated with Clostridium perfringens type C infection. Infections may be sporadic or occur as outbreaks in multiple foals on a farm. Severe depression and rapid deterioration of cardiovascular status is followed by death in 24-48 hr in most cases. Other bacteria that have been associated with diarrhea in foals are Bacteroides fragilis , Clostridium difficile , Aeromonas hydrophila , and Rhodococcus (Corynebacterium) equi . The first three occur in foals <2 wk old and require intensive supportive care. Although R equi primarily causes respiratory disease, both acute and chronic enteritis can occur; diarrhea is seen in foals 1-4 mo old. The diagnosis is more straightforward if pneumonia is also present. When cultured from tracheal wash fluid, R equi is considered a pathogen; however, a positive fecal culture is not as helpful because R equi can be found in the feces of healthy foals. Erythromycin combined with rifampin is the treatment of choice for R equi infection in foals. Viral Diarrhea in Foals: Viruses appear to cause diarrhea in foals but not in adult horses. Rotavirus is the main cause of viral diarrhea in foals; however, other viruses, such as coronavirus, have been implicated. Diarrhea induced by rotavirus is characterized by depression; anorexia; and profuse, watery, malodorous feces. It is usually seen in foals <2 mo old; younger foals typically have more severe clinical signs. The diarrhea usually lasts 4-7 days, although it can persist for weeks.

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Rotavirus destroys the absorptive enterocytes in the small intestine, which results in malabsorption. Lactase becomes deficient, so lactose passing into the large intestine induces an osmotic diarrhea. Diagnosis is made by identification of virus in the feces by electron microscopy, ELISA, or agglutination test. Treatment is generally supportive. Personnel should wear disposable gloves and boots and wash their hands with 10% povidone-iodine soap before and after handling diarrheic foals. Foot dips containing phenolic disinfectants outside the stall of the sick foal should also be used. Bleach, chlorhexidine, and quaternary compounds do not appear to be effective disinfectants for rotavirus. Arriving horses and foals, including those returning from veterinary hospitals, should be isolated for ≥7 days before being introduced to the resident population. A vaccine for prevention of rotavirus infection in foals is not available. Miscellaneous Causes of Diarrhea in Foals: Nutritional diarrhea can result from overfeeding (eg, when a foal is reunited with the mare after a period of separation) and improper nutrition (eg, orphan foals being fed calf milk replacer or sucrose). Lactose intolerance in foals is rare . Diarrhea can also occur when foals consume indigestible substances such as roughage, sand, dirt, and rocks. Porcine Edema Disease (Escherichia coli enterotoxemia) Edema disease is an acute, highly fatal, neurologic disorder that usually occurs 5 days to 2 wk after weaning and may be accompanied by diarrhea. Porcine Proliferative Enteritis (Porcine intestinal adenomatosis, Proliferative hemorrhagic enteropathy, Ileitis) Porcine proliferative enteritis is a common diarrheal disease of growing-finishing and young breeding pigs characterized by hyperplasia and inflammation of the ileum and colon. It often is mild and self-limiting but sometimes causes persistent diarrhea, severe necrotic enteritis, or hemorrhagic enteritis with high mortality. Etiology and Pathogenesis: The etiology is the recently classified intracellular bacterium Lawsonia intracellularis . Clinical Findings: The more common, nonhemorrhagic form of the disease often affects 40- to 80-lb (18- to 36-kg) pigs and is characterized by sudden onset of diarrhea. The feces are watery to pasty, brownish, or faintly blood stained. After ~2 days, pigs may pass yellow fibrinonecrotic casts that have formed in the ileum. Most affected pigs recover spontaneously, but a significant number develop chronic necrotic enteritis with progressive emaciation. The hemorrhagic form is characterized by cutaneous pallor, weakness, and passage of hemorrhagic or black, tarry feces. Pregnant gilts may abort. Lesions: Lesions may occur anywhere in the lower half of the small intestine, cecum, or colon but are most frequent and obvious in the ileum. The wall of the intestine is thickened, and the mesentery may be edematous. The mesenteric lymph nodes are enlarged. The intestinal mucosa appears thickened and rugose, may be covered with a brownish or yellow fibrinonecrotic membrane, and sometimes has petechial hemorrhages. Diagnosis: Confirmation is based on histologic observation of characteristic proliferation and inflammation of mucosal crypts. Lawsonia intracellularis (comma-shaped resembling Campylobacter ) can usually be demonstrated by silver stains. A polymerase chain reaction (PCR) test has been developed and may be useful for confirmation of the presence of L intracellularis in lesions. Rotaviral Enteritis Rotaviral enteritis is a common disease of the small intestine of pigs. All ages are susceptible, but significant diarrheal disease usually occurs in nursing or postweaning pigs. Etiology and Pathogenesis: The causal rotavirus infects and destroys villous enterocytes throughout the small intestine, but lesions are most severe in the middle third of the intestine. Loss of villous epithelium results in partial villous atropy, malabsorption, and osmotic diarrhea. Healthy carrier sows may be fecal shedders during the periparturient period, thereby exposing their litters to infection. Clinical Findings and Lesions: If neonatal pigs do not receive protective levels of maternal antibody, they are likely to develop profuse watery diarrhea in 12-48 hr. More commonly, the infection is endemic in a herd, and sows have varying levels of antibody in the colostrum and milk, which provide varying degrees of passive protection to nursing pigs. Diarrhea often begins in pigs 5 days to 3 wk old, or immediately after weaning. The feces of nursing pigs often are yellow or gray and pasty in the early stages and
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progress to gray and pasty after ~2 days. Diarrhea persists for 2-5 days. Diarrheic pigs become gaunt and rough-haired, but mortality usually is low. Weaned pigs have watery feces that contain poorly digested feed. Diagnosis: Confirmation is based on histologic demonstration of villous atrophy in the jejunum, electron microscopical demonstration of virions in the intestinal contents, and immunodiagnostic procedures to demonstrate viral antigen in the intestinal mucosa or feces. Differential diagnoses include endemic transmissible gastroenteritis, Isospora suis enteritis, and enteric colibacillosis. Treatment and Control: There is no specific treatment. Swine Dysentery (Bloody scours) Swine dysentery is a common, mucohemorrhagic diarrheal disease of pigs that affects the large intestine. Etiology and Pathogenesis: The essential causal agent is Serpulina (Treponema) hyodysenteriae , an anaerobic spirochete that produces a hemolysin, although other organisms may contribute to the severity of lesions. It proliferates in the large intestine and causes degeneration and inflammation of the superficial mucosa, hypersecretion of mucus by mucosal epithelium, and multifocal bleeding points on the mucosal surface. The organism does not penetrate beyond the intestinal mucosa. Decreased ability of the mucosa to reabsorb endogenous secretions from the unaffected small intestine results in diarrhea. Clinical Findings: More commonly, a mucoid diarrhea with flecks of blood and mucus develops and progresses to a watery mucohemorrhagic diarrhea. After several days, the feces are brown and contain flecks of fibrin and debris. Diarrheic pigs are dehydrated, profoundly weak, gaunt, and emaciated. Lesions: The diffuse lesions are confined to the cecum, spiral colon, and rectum. The affected mucosa is covered with a layer of transparent or gray mucus, often with suspended flecks of blood in early stages; a mixture of blood, fibrin, and necrotic debris in more advanced cases; and a yellow, necrotic debris late in the course. Diagnosis: Clinical signs and necropsy findings are usually sufficient for a presumptive diagnosis. Differential diagnoses include proliferative enteritis, salmonellosis, and heavy whipworm infections. Treatment and Control: Therapeutic use of antibacterials is effective if started early. Bacitracin, carbadox, lincomycin, nitroimidazoles, tiamulin, and virginiamycin are commonly used. Transmissible Gastroenteritis Transmissible gastroenteritis (TGE) is a common viral disease of the small intestine that causes vomiting and profuse diarrhea in pigs of all ages. Etiology and Pathogenesis: The causal coronavirus infects and destroys villous epithelial cells of the jejunum and ileum, which results in severe villous atrophy, malabsorption, osmotic diarrhea, and dehydration. The incubation period is ~18 hr. Recovered pigs can carry the virus in their respiratory tract for ≥4 mo. Severe epidemics are more common during winter due to survival of the virus in colder temperatures. Clinical Findings: In nonimmune herds, vomiting often is the initial sign, followed by profuse watery diarrhea, dehydration, and excessive thirst. Feces of nursing pigs often contain curds of undigested milk. Mortality is nearly 100% in piglets <1 wk old, whereas pigs >1 mo old seldom die. Gestating sows occasionally abort and lactating sows often exhibit vomiting, diarrhea, and agalactia. Immunity from antibody in the sow's milk usually is sufficient to protect pigs until they are 4-5 days old. As the antibody level in milk decreases, infection and mild disease may occur. If passive protection is sufficient to protect pigs throughout the nursing period, diarrhea often develops during the first few days after weaning. Lesions: Piglets dying of TGE are severely dehydrated, and the skin is soiled with liquid feces. The stomach usually contains milk curd but may be empty. The small intestine is thin walled, and the entire intestine contains greenish or yellow watery fluid and clumps of undigested milk. Older pigs have few remarkable lesions except that the colon contains liquid rather than formed feces. Villous atrophy can be observed by examining the mucosa of the small intestine with a hand lens. Diagnosis: In some outbreaks, coronaviral encephalomyelitis may cause similar signs. Treatment and Control:
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There is no specific treatment. Increasing farrowing room temperature to minimize body heat loss and providing electrolyte solutions to combat dehydration are helpful. Active, protective immunity develops after TGE infection of the intestinal mucosa. Parenteral injection of sows with TGE vaccine elicits high levels of antibody in the colostrum but only low levels of antibody in the postcolostral milk. Oral and parenteral administration of vaccine offers somewhat better protection because infection of the intestine elicits a secretory IgA response. Active infection of the intestine with virulent virus provides protective immunity for 6-18 mo. Vaccination of naturally immune sows boosts immunity sufficiently to protect neonates and is particularly useful in endemically infected herds. Planned infection of pregnant sows in herds known to be infected with virulent virus at least 2-4 wk before farrowing usually provides adequate immunity. This may be accomplished by mixing ground, TGE-virus-infected intestine and feces in the gestation ration. Because of the obvious hazards associated with this procedure, it should be undertaken only if a later epidemic in the farrowing house seems inevitable. The infectious material should be used only in the same herd from which it was collected, and the tissues should be as free as possible from other pathogens of pigs. TGE virus is easily spread during an epidemic by persons, animals, and fomites. Winter Dysentery: Introduction Winter dysentery is an acute, highly contagious GI disorder that affects housed dairy and beef cattle, primarily during winter. Clinical features include an explosive onset of dark, hemorrhagic diarrhea and a dramatic drop in milk production. Winter dysentery most frequently affects young adult dairy cattle; pregnant, recently calved, or lactating animals are the most severely affected. The disease also has been reported in steers and beef bulls. Etiology: The precise etiology is unclear. In recent years, a bovine coronavirus (BCV), closely related to the virus that causes diarrhea in neonatal calves, has been implicated as the etiologic agent. Transmission, Epidemiology, and Pathogenesis: Mortality rates associated with winter dysentery are generally low (1-2%), but morbidity in affected herds is high (50100%). Coronaviruses survive best at low temperatures and at low ultraviolet light intensities, which could lead to a buildup of virus in the environment during the colder months. The pathogenesis of winter dysentery has been attributed to the presence of colonic mucosal lesions. Destruction of epithelial cells in the colonic crypts leads to transudation of extracellular fluid and blood, which explains the hemorrhagic nature of the diarrhea. Inflammatory mediators that cause hypersecretion in the small intestine and colon may contribute to the voluminous diarrhea seen in affected cattle. Clinical Findings and Diagnosis: Feces vary from light brown to dark tan; blood may be present as small streaks or large clots, or it may be uniformly mixed in the feces. A sweet, musty, unpleasant odor is detected in barns with large numbers of affected cattle. Other signs include mild colic, dehydration, anorexia, depression, and weight loss. Nasolacrimal discharge or cough may accompany or precede the diarrhea. Clinical disease lasts a few days in smaller herds and several weeks in large herds. Differential diagnoses, including bovine viral diarrhea, coccidiosis, salmonellosis, and parasitic gastroenteritis, are excluded by negative fecal flotation, absence of mucosal lesions, negative fecal cultures for Salmonella spp , and observation of rapid onset of diarrheal disease with a high morbidity. Lesions: Histologic findings in the colon include necrosis of the glandular epithelial cells. Small animal Dilatation of the Esophagus (Megaesophagus) Esophageal dilatation in young animals may be the result of a vascular ring anomaly or due to an unknown cause. Idiopathic megaesophagus may also occur in adult dogs, and the esophagus may dilate secondary to or associated with systemic diseases such as myasthenia gravis, systemic lupus erythematosus, polymyositis, distemper, hypoadrenocorticism, heavy metal toxicity, hypothyroidism, CNS neoplasia, or trauma. The cardinal sign is regurgitation. A puppy with congenital megaesophagus characteristically begins to regurgitate at weaning when it begins to eat solid food. Initially, regurgitation occurs soon after swallowing; as the condition progresses, the esophagus enlarges and food is retained longer. Affected pups are generally unthrifty and smaller than their littermates. Pressure applied to the abdomen may cause ballooning of the esophagus at the thoracic inlet. Aspiration pneumonia is a common complication, and the associated signs are fever, cough, and nasal discharge. In adult dogs, associated diseases (eg, myasthenia gravis) should be treated. Surgery is indicated for a vascular ring anomaly. Feeding from an elevated dish that requires the dog to eat with forelimbs higher than hindlimbs or holding the dog

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in an upright position for 10-15 min after eating allows gravity to assist food passage into the stomach. The overall prognosis is poor, and many die from aspiration pneumonia. Mouth Burns Thermal, chemical, or electrical burns involving the mouth are not uncommon. Chewing on an electrical cord is most frequently a problem in puppies. If tissue destruction is marked, ulcerative or gangrenous stomatitis may develop, with secondary bacterial infections. If contact with a corrosive chemical is seen and the chemical is alkaline, the mouth may be flushed with mild solutions of vinegar or citrus juice; if the chemical is acidic, a solution of sodium bicarbonate may be used. Copious flushing of the mouth with water may help remove some of the chemical substances. Malignant Oral Neoplasms Tumors of the mouth and pharynx are common and likely to be malignant. In dogs, the three most common are malignant melanoma, squamous cell carcinoma, and fibrosarcoma. The gingiva is affected most frequently. Incidence of malignant oral tumors is greater in dogs >8 yr old, and Cocker Spaniels and German Shepherd Dogs may be predisposed to developing oral malignant melanomas. Squamous cell carcinomas are by far the most common malignant oral neoplasms in cats; they commonly involve the gingivae and tongue and are locally highly invasive. Fibrosarcomas are the next most common; in cats, they are locally invasive and have a poor prognosis. Clinical Findings: Signs vary depending on the location and extent of the neoplasm. Halitosis, reluctance to eat, and hypersalivation are common. The tumors frequently ulcerate and bleed. The face may become swollen as the tumor enlarges and invades surrounding tissue. Regional lymph nodes often become swollen before oral and pharyngeal tumors are seen. Diagnosis: Biopsy is usually required for definitive diagnosis. Malignant melanomas are variable in appearance, pigmented or nonpigmented, and should be considered in the diagnosis of any oral tumor. Squamous cell carcinomas commonly involve the gingivae or tonsils, and lymphosarcoma should be a differential diagnosis for an enlarged tonsil. Regional lymph nodes and the lungs should be evaluated for metastases. Treatment: Malignant melanomas are highly invasive and metastasize readily; consequently, the prognosis is poor. Tonsillar squamous cell carcinomas are aggressive and have a poor prognosis. Fibrosarcomas have a poor prognosis because of their locally aggressive nature. In cats, squamous cell carcinoma has a poor prognosis, and long-term survival is seen only if diagnosed early. Local tumor removal is possible by hemimandibulectomy. Salivary Mucocele: In a salivary mucocele (or sialocele), mucoid saliva accumulates in the subcutaneous tissue after damage to the salivary duct or gland. This is the most common salivary gland disorder of dogs. While any of the salivary glands may be affected, the sublingual and mandibular glands are involved most commonly. Usually the saliva collects at the intermandibular or cranial cervical area (cervical mucocele). The cause may be traumatic or inflammatory blockage or rupture of the duct of the sublingual, mandibular, parotid, or zygomatic salivary gland. The first noticed sign may be a nonpainful, slowly enlarging, fluctuant mass, frequently in the cervical region. A ranula may not be seen until it is traumatized and bleeds. A pharyngeal mucocele may obstruct the airways and result in moderate to severe respiratory distress. A mucocele is detectable as a soft, fluctuant, painless mass that must be differentiated from abscesses, tumors, and other retention cysts of the neck. Pain or fever may be present if the mucocele becomes infected. A salivary mucocele usually can be diagnosed by palpation and aspiration of the characteristic golden or blood-tinged, stringy saliva. Usually, careful palpation with the animal in dorsal recumbency can determine the affected side; if not, sialography may be helpful. Surgery is recommended to remove the damaged salivary gland and duct, usually of the mandibular-sublingual gland complex. Cervical mucoceles can be managed with periodic drainage if surgery is not an option. Drainage, marsupialization, or gland removal has been recommended for treatment of ranulas. Complete gland and duct removal is recommended for pharyngeal mucoceles to avoid future life-threatening airway obstruction. Canine Parvovirus: Introduction Etiology and Pathophysiology:
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The origin of the canine parvovirus has not been established. The virus is very stable in the environment, able to withstand wide pH ranges and high temperatures. Rottweilers, American Pit Bull Terriers, Doberman Pinschers, and German Shepherd Dogs are at increased risk of disease. Toy Poodles and Cocker Spaniels appear at decreased risk for developing the enteric disease. Recovered dogs may serve as carriers and shed the virus periodically. After ingestion, the virus replicates in lymphoid tissue of the oropharynx; from there, it spreads to the bloodstream. It attacks rapidly dividing cells throughout the body, especially those in the bone marrow, lymphopoietic tissue, and the crypt epithelium of the jejunum and ileum. Replication in the bone marrow and lymphopoietic tissue causes neutropenia and lymphopenia, respectively. Replication of the virus in the crypt epithelium of the gut causes collapse of intestinal villi, epithelial necrosis, and hemorrhagic diarrhea. Normal enteric bacteria, eg, Clostridium perfringens and Escherichia coli enter the denuded mucosa and gain entry to the bloodstream, resulting in bacteremia. Clinical Findings: Infected dogs are often asymptomatic. Clinical disease may be triggered by stress (eg, boarding), and clinical signs may be exacerbated by concurrent infection with opportunistic enteric pathogens. Initially, two common clinical forms of the disease were recognized—myocarditis and gastroenteritis. Myocarditis was seen in young pups, especially in the early neonatal period. Myocarditis is no longer seen because effective immunization of bitches protects pups during this early period of life. Gastroenteritis is most common in pups 6-20 wk old, ie, the period when maternal antibody protection falls and vaccination has not yet adequately protected the pup against infection. Most affected dogs (~85%) are <1 yr old. In dogs >6 mo old, intact males are more likely to develop enteritis than intact females, reflecting the tendency of male dogs to roam. Dogs with the enteric form suffer from an acute onset of lethargy, anorexia, fever, vomiting, and diarrhea. The feces are loose and may contain mucus or blood. The severity of clinical signs varies. Most dogs recover within a few days with appropriate supportive care. Other clinical problems that have been associated with canine parvovirus include birth defects and infertility. However, supportive evidence is lacking. Diagnosis: Diagnosis is based on an appropriate history and the clinical signs and confirmed by a positive fecal ELISA test or hemagglutination test. Leukopenia or lymphopenia is seen in most infected dogs during the course of illness. Hypoalbuminemia, hyponatremia, hypokalemia, and hypochloremia may be seen. Treatment: There is no specific therapy to eliminate the virus. Most dogs recover with appropriate supportive care directed to restoration of fluid balance. Oral electrolyte solutions may be used in mildly dehydrated dogs without a history of vomiting. More severely affected dogs should receive IV fluid therapy (lactated Ringer's and 5% dextrose with additional potassium chloride [10-20 mEq/L]) to counter dehydration and maintain fluid balance. Persistent vomiting can be controlled with metoclopramide, 0.2-0.5 mg/kg, q.i.d., PO or SC, or 1-2 mg/kg/day, slow IV). Routine use of antibiotics is discouraged. In more severe cases (eg, those with severe blood loss, fever, or loss of intestinal integrity), intestinal integrity is compromised, and these dogs are predisposed to bacteremia and septicemia. In these cases, trimethoprim-sulfa (15 mg/kg, b.i.d., SC or PO) for 5-10 days is advisable; in more severe cases, ampicillin (20 mg/kg, t.i.d., IV) and gentamicin (2.2 mg/kg, t.i.d., SC) for a maximum of 5 days is advisable. Food and water should be withheld until vomiting has subsided. After this, small amounts of a bland diet (eg, cottage cheese and rice or a commercially available prescription diet such as Canine i/d® [Hill's]) should be offered frequently. Prevention and Control: Pups should be kept isolated from adult dogs returning from shows or field trials. Vaccination is critical in the control of the disease. Constipation And Obstipation: Introduction Constipation is a common clinical problem in small animals. Obstipation is intractable constipation, in which the animal is unable to successfully defecate. Etiology and Pathophysiology: Chronic constipation may be due to intraluminal, extraluminal, or intrinsic (ie, neuromuscular) factors. Intraluminal obstruction occurs most commonly and is due to the inability to pass poorly digestible, often firm matter (eg, hair, bones, litter) mixed with fecal material. Intraluminal tumors may also impede the passage of feces. Extraluminal obstruction may be caused by compression of the colon or rectum by a narrowed pelvic inlet or by compression of the colon or rectum by enlarged sublumbar lymph nodes or prostate gland. Colonic stricture due to trauma or neoplasia should also be considered. Finally, some animals (usually cats) with chronic constipation or obstipation may have megacolon, likely caused by a lesion of the neuromuscular bed of the colon. The etiology of megacolon often remains undiagnosed. Other diseases that affect neuromuscular control of the colon and rectum include hypothyroidism, dysautonomia, and lesions of the spinal cord or pelvic nerves. Hypokalemia and hypercalcemia also adversely affect muscular control. Some drugs (eg, opioids, diuretics,
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antihistamines, anticholinergic agents, sucralfate, aluminum hydroxide, and calcium channel-blocking agents) promote constipation via differing mechanisms. Clinical Findings: The classic clinical signs are tenesmus and the passage of firm, dry feces. If the passage of feces is hindered by an enlarged prostate or sublumbar lymph nodes, the feces may appear thin or “ribbon-like” in appearance. Abdominal palpation and rectal examination confirms the presence of large volumes of retained fecal matter. Diagnosis: A history of dietary indiscretion and physical evidence of retained feces confirms the diagnosis. Abdominal palpation and rectal examination, including evaluation of the prostate and sublumbar lymph nodes, should be completed. A complete blood count, biochemical profile including a serum T4 level, urinanalysis, and detailed neurologic examination should be completed in cases of chronic or recurring constipation. Treatment and Control: Affected animals should be adequately hydrated. In more severe cases, retained feces must be evacuated using enemas or manual extraction while under general anesthesia. Complete removal of all feces may require two or three attempts over as many days. Concurrent fluid and electrolyte abnormalities should also be corrected. Laxatives are classified as bulk-forming, lubricant, emollient, osmotic, or stimulant types. Most act on fluid transport mechanisms and colonic motor stimulation. They should be avoided in the presence of dehydration. High-fiber bulkforming laxatives are added to the diet. These products absorb water, soften feces, add bulk, stretch the colonic smooth muscle, and improve contractility. Supplementation of the diet with fiber (eg, 1-6 tsp per feeding of psyllium hydrophilic mucilloid, or 1-4 tbsp of coarse wheat bran) is adequate. For long-term control of constipation, high-fiber diets (eg, Canine w/d ®[Hill's]) should be fed. Mineral oil (5-25 mL, b.i.d., PO) and petrolatum products are lubricants and are given to affected animals between meals. Mineral oil should be flavoured to avoid accidental inhalation of this otherwise tasteless product. Docusate sodium (cats: 50-mg capsule, s.i.d.; dogs: 50-mg capsule, 1-4/day) and docusate calcium (cats: 50-mg capsule, 1-2/day; dogs: 50-mg capsule, 2-3/day) are emollient laxatives. Osmotic laxatives (eg, lactulose, 0.5 mL/kg, every 8-12 hr, PO) osmotically retain water in the bowel to soften fecal material. Lactulose, a nonabsorbable disaccharide, is also useful in management of hepatic encephalopathy by virtue of the fact that it decreases luminal pH, reduces the bacterial production of ammonia, and favors the formation of ammonium ions which are poorly absorbed. Stimulant laxative products (eg, bisacodyl [cats and small dogs: 5 mg; medium-sized dogs: 10 mg; large dogs: 15-20 mg]) increase the propulsive activity of the bowel. They are contraindicated in the presence of bowel obstruction. Enema solutions are frequently used to moisten and soften feces making them easier to pass. Sodium phosphate enemas are sometimes used to relieve constipation in dogs but should not be used in the face of dehydration, cardiac disease, nausea, or vomiting. They are also contraindicated in small dogs and cats and in animals with renal dysfunction. Mineral oil (5-20 mL) can be directly instilled into the rectum to help facilitate passage of hard feces. Chronic constipation that has been unresponsive to medical management may respond to subtotal or total colectomy. Gastric Dilatation-volvulus: Introduction (Bloat) Gastric dilatation-volvulus (GDV) is a life-threatening emergency. Etiology and Pathophysiology: GDV tends to primarily affect large, deep-chested dogs. Doberman Pinschers, German Shepherd Dogs, Standard Poodles, Great Danes, Saint Bernards, Irish Setters, and Gordon Setters are affected most commonly. Dilatation likely precedes volvulus. Dilatation occurs secondary to the accumulation of gas or fluid (or both) within the stomach, the outflow from which is obstructed. Obstruction may be caused by neoplasia, pyloric stenosis, foreign body, or compression of the duodenum against the body wall by the expanding stomach. Distention of the stomach by gas may be associated with aerophagia, diffusion from the bloodstream, release of carbon dioxide after the reaction of hydrochloric acid and bicarbonate, or bacterial fermentation. Viewed from a caudal to cranial direction, the stomach rotates 90-360° in a clockwise fashion about the distal esophagus. If the volvulus is >180°, the distal esophagus becomes occluded. Clinical Findings: Clinical signs may include an acute onset of restlessness, apparent discomfort, abdominal pain, repeated unproductive retching, excessive salivation, and abdominal distention. Progression to volvulus predisposes to hypovolemic shock. Abnormalities on physical examination include tachypnea or dyspnea, rapid and weak pale mucous membranes, and prolonged capillary refill time indicative of hypovolemic shock. An irregular heart rate and associated pulse deficits indicate cardiac arrhythmias. Decrease in venous return, cardiac output, and arterial blood pressure, as well as hypovolemic shock, are caused by compression of the caudal vena cava; sequestration of blood in dilated splanchnic, renal, and posterior muscular capillary beds; loss of fluid into the obstructed stomach; and a lack of water intake. Endotoxemia, hypoxemia, metabolic acidosis, and hypotension predispose to disseminated intravascular coagulation.
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Diagnosis: A history of ingestion of a large meal followed by exercise and repeated attempts to vomit is common. Dogs not in a state of shock may appear anxious. Hypersalivation and abdominal distention with gas are noted on physical examination. Abdominal radiographs taken in right lateral recumbency are preferred for the diagnosis of volvulus. Systemic hypotension predisposes to prerenal azotemia with increases in serum urea and creatinine concentrations. Serum phosphorus increases similarly. After decompression and the “wash out” of sequestered blood, serum levels of ALT and AST increase. Creatinine kinase levels also increase due to striated muscle damage, and serum potassium levels increase subsequent to cell membrane injury. Treatment and Control: The principal goals of initial treatment are to stabilize the animal and decompress the stomach. Metabolic acidosis frequently accompanies GDV. Gastric decompression should be accomplished as soon as possible. Initially, an attempt should be made to pass a welllubricated orogastric (or stomach) tube. The distance from the incisors to the xiphoid or costal arch should be measured, and this distance on the stomach tube marked by a piece of tape. This distance indicates the maximum length of tube that can be safely passed; marking this length decreases the likelihood of passing the stomach tube through a devitalized stomach wall. Once the tube enters the stomach, gastric gas readily escapes. Excess fluid and ingesta are removed via gravity and suction. Splenic congestion generally resolves after the stomach has been repositioned. Gastric wall resection or splenectomy is reserved for cases in which tissue viability has been compromised. Most dogs that die of GDV (70%) do so within the first 4 days after surgery. Many dogs develop ventricular arrhythmias, the cause of which may include myocardial ischemia, autonomic imbalance, acid-base and electrolyte imbalance, catecholamine release, and the release of myocardial depressant factor. Arrhythmias that warrant medical therapy include those that significantly impair cardiac output, multifocal premature ventricular contractions, a ventricular rate persistently >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:
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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.
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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 <2 yr old. Clinical signs are often chronic and sometimes cyclic or intermittent. Vomiting, diarrhea, changes in appetite, and weight loss may be seen. Vomiting, melena, and cranial abdominal pain are often seen with gastroduodenal ulceration and erosion. When erosion or ulceration does occur, it occurs most often in the areas that do not produce acid (ie, the fundus, antrum, and pylorus). The duodenum has also been implicated as a frequent site for this problem. Clinical signs of large-intestinal diarrhea, including anorexia and watery diarrhea, are not uncommon. Diagnosis: Thickened intestinal loops may be palpated in >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.
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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
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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 (<1.5 g/dL). Microhepatica and renomegaly are usually noted on abdominal radiographs. Treatment: The treatment of choice for single congenital PSS is surgical ligation. Whether ligation is total or partial depends on portal pressures (should be <20 cm H2O). If only partial ligation can be achieved at the time of the first surgery, then additional surgery may be indicated if clinical signs do not resolve. Mortality associated with surgery is estimated at ~20%. The most common postsurgical complication is acute portal hypertension, which manifests as accumulation of abdominal effusion, bloody diarrhea, abdominal pain, ileus, and endotoxic shock. If this occurs, immediate medical treatment for shock and removal of the ligature is necessary. In the case of multiple shunts, as in acquired PSS, or in instances in which either surgery is not possible or clinical signs are minor, medical management can be used to control clinical signs. Poor prognosis after 2 yr of age is attributed to progressive liver atrophy. Feline Idiopathic Hepatic Lipidosis Feline idiopathic hepatic lipidosis is a disease of undetermined etiology that is associated with a period of anorexia (few days to several weeks), especially in obese cats. Factors that may trigger anorexia include a change of diet to initiate weight loss or other stressful events (eg, moving, boarding, death of other pets or owners). Secondary hepatic lipidosis is associated with either a primary metabolic (eg, diabetes mellitus) or GI disease (eg, inflammatory bowel disease, gastric foreign bodies, pancreatitis, or cholangiohepatitis) that can cause anorexia. Regardless of the inciting cause, the end result is excessive accumulation of triglycerides (fat) within the liver, which leads to severe intrahepatic cholestasis and hepatic failure. Clinical Findings: Clinical signs are variable but can include dramatic weight loss (30-40%, experimentally) due to anorexia, vomiting, lethargy, and diarrhea. Laboratory abnormalities include a nonregenerative, normocytic, normochromic anemia; stress leukogram; hyperbilirubinemia and bilirubinuria; mildly increased AST and ALT, and increased AP and serum bile acids.
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GGT values are usually normal. Occasionally, hypoalbuminemia, prolonged coagulation profile, and hyperammonemia have been reported. If the cat is not icteric, bile acids can be evaluated. Treatment: Treatment is primarily supportive, unless an underlying cause can be found. Fluid therapy, with a polyionic, isotonic solution supplemented with potassium and thiamine, is recommended to correct dehydration. Administration of dextrose fluids can exacerbate signs of hepatic encephalopathy by stimulating hepatic fat synthesis and should be avoided unless the cat is hypoglycemic. Feeding as soon as possible is essential. Occasionally, appetite stimulants (eg, diazepam or cyproheptidine) may be helpful. However, long-term use of diazepam can have a negative effect on the liver. A highprotein, calorie-dense, balanced diet is recommended unless the cat shows signs of hepatic encephalopathy, in which case a low-protein diet should be used. Vomiting associated with tube feeding can be controlled with metoclopramide or cisapride. Another complication associated with tube feeding is hypophosphatemia, which can lead to hemolytic anemia; therefore, phosphorus levels should be routinely evaluated. Gastritis can be controlled with H2-blockers (eg, famotidine or ranitidine) and carafate. If clinical signs of hepatic encephalopathy are present, lactulose and metronidazole are also recommended. If pancreatitis is concurrent, total parenteral nutrition may be necessary to prevent pancreatic secretions. Prognosis is good if the diagnosis is made early, treatment is begun, and the underlying disease, if any, can be treated. Concurrent pancreatitis is a poor prognostic indicator. Monitoring AP of obese cats on a weight-reducing diet may be effective in preventing hepatic lipidosis from occurring. Early dietary support for obese cats that become anorectic because of other underlying disease is also recommended. Cholangitis And Cholangiohepatitis: Overview (Inflammatory liver disease) Cholangitis and cholangiohepatitis are common in cats but rare in dogs. The classic classification for inflammatory liver disease in cats includes suppurative (acute) cholangitis and cholangiohepatitis, nonsuppurative (chronic) or lymphocytic cholangitis and cholangiohepatitis, and biliary cirrhosis. Recently, a lymphocytic portal hepatitis has been reported. Cholangitis is defined as inflammation of the biliary system. In cholangiohepatitis, inflammation extends into the hepatic parenchyma. Biliary cirrhosis refers to portal fibrosis and biliary hyperplasia that occurs after long-term inflammation. Over several years, cholangiohepatitis can lead to cirrhosis and end-stage liver disease. Suppurative Cholangitis and Cholangiohepatitis Suppurative (acute) cholangitis and cholangiohepatitis is often associated with bacterial, fungal, or protozoal infections, or less frequently, liver fluke infection. It is suspected that the bacteria originate from the gut and ascend via the bile duct due to some predisposing condition, such as biliary stasis, choleliths, chronic pancreatitis, inflammatory bowel disease, or anatomic abnormalities. Clinical signs are usually of short duration and include fever, hepatomegaly, abdominal pain, icterus, lethargy, vomiting and anorexia. Laboratory abnormalities include neutrophilia with left shift; nonregenerative anemia; hyperbilirubinemia; moderate increases in ALT, AST, and GGT; and a mild increase in AP. Serum bile acids are usually increased, especially postprandial values. Cholestasis and inspissation of bile can cause extrahepatic biliary obstruction and can predispose to cholelith formation. Use of corticosteroids is controversial; an anti-inflammatory dose can be tried if there is no response to antibiotic therapy. If extrahepatic biliary obstruction is not present, ursodeoxycholic acid can be used as a choleretic. Nonsuppurative or Lymphocytic Cholangitis and Cholangiohepatitis Nonsuppurative, chronic, or lymphocytic cholangitis and cholangiohepatitis has a lymphocytic-plasmacytic component, suggesting an underlying immune condition. Nonsuppurative cholangitis is considered to be a chronic condition, often seen in association with chronic pancreatitis, inflammatory bowel disease, or fluke infections. Incidence may be higher in Persian cats. Ascites and icterus are the most common clinical signs, and lymphadenopathy may be present. If the disease has progressed to cirrhosis, then clinical signs of hepatic encephalopathy may also be seen. Prednisone (0.5-1 mg/lb, PO, s.i.d.) therapy is recommended in the nonsuppurative form of the disease because of the suspected immune-mediated component. Prognosis is variable. Biliary Cirrhosis Biliary cirrhosis is uncommon, possibly because animals die before reaching this condition. Biliary cirrhosis is thought to be the end-stage of suppurative and nonsuppurative cholangitis and cholangiohepatitis, or it may be a distinctly different disease. Clinical signs include icterus, hepatomegaly, cachexia, and ascites. Liver enzymes may be normal. Hypoalbuminemia, hyperglobulinemia, hyperbilirubinemia, and coagulopathies are common laboratory abnormalities. Often, coagulation defects necessitate a whole blood transfusion before a biopsy can be taken. Treatment is symptomatic. Higher-protein diets are recommended to correct hypoalbuminemia unless hepatic encephalopathy is present. Spironolactone can be used with furosemide to control ascites. Corticosteroids are contraindicated. Ursodeoxycholic acid may slow progression of cirrhosis. Prognosis is poor.
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Hepatic Neoplasia Metastatic neoplasia of the liver is more common than primary hepatic neoplasia and can arise from many organs, including pancreas, spleen, GI tract, adrenal gland, mammary gland, and lungs. These tumors can be either carcinomas or sarcomas. Primary tumors are seen in older animals (>10 yr) and can be either neoplastic or benign. They include hepatocellular adenomas and carcinomas, biliary adenomas and carcinomas, and hemangiosarcomas. Bile duct adenomas are more common in cats than in dogs and are of little clinical significance; a single, large mass can be seen in dogs. Hepatocellular carcinomas are the most common primary liver tumor in male dogs; biliary carcinomas are more frequently reported in female dogs. Lymphoma is the most common hemolymphatic tumor found in the liver in both dogs and cats. Lymphosarcoma of the liver is often seen with lymphosarcoma of the intestines and stomach. The most common metastatic tumors in dogs include pancreatic carcinoma, mammary carcinoma, pheochromocytoma, intestinal carcinoma, and thyroid carcinoma, fibrosarcoma, osteosarcoma, and transitional cell carcinoma. Animals with lymphoma or myeloproliferative disease may have circulating blast cells. Eosinophilia can be seen with mast cell tumors. Liver enzymes are generally increased more frequently with primary tumors than with metastatic disease. AP and ALT are often increased in dogs; ALT and AST are increased in cats. The prognosis is poor for primary hepatic tumors that involve multiple lobes. Vomiting: Introduction Vomiting is the forceful ejection of the contents of the stomach and proximal small intestine. It is a vigorously active motion signalled by hypersalivation, retching, and forceful contractions of the abdominal muscles and the diaphragm. Vomiting must be differentiated from regurgitation, which is a passive motion facilitated by gravity and body position of the animal. In regurgitation, the expelled food and fluid tends to be undigested, has a neutral pH depending on the composition of the diet, and may have a cylindrical shape reflecting the shape of the esophagus. Etiology, Pathophysiology, and Clinical Findings: Vomiting represents a coordinated effort of the GI, musculoskeletal, and nervous systems to expel food, fluid, or debris from the GI tract. It is initiated by direct stimulation of the vomiting center in the brain stem or indirectly via the chemoreceptor trigger zone (CTZ) or abdominal afferent nerves. Stimulation of receptors in the semicircular canals of the vestibular system, or inflammation within the CNS and increases in intracranial pressure, can also promote vomiting. The CTZ responds to substances in the blood, eg, drugs, ketones, or uremic or bacterial toxins. Most of the receptors involved in the vomiting reflux are found in the abdominal viscera, especially in the duodenum. Vomiting can be due to primary GI disease, renal or hepatic failure, electrolyte abnormalities (eg, hypoadrenocorticism), pancreatitis, or CNS disorders (including toxin ingestion). Diagnosis: The diagnostic approach to vomiting varies depending on whether the vomiting is acute or chronic. Chronic vomiting may be associated with weakness, lethargy, weight loss, dehydration, electrolyte imbalance, and acid-base disorders. Chronic vomiting, vomiting that occurs more often than once or twice daily, and vomiting accompanied by hematemesis, abdominal pain, depression, dehydration, weakness, fever, or other adverse clinical signs should be approached more vigorously. In addition to a detailed history and physical examination, an initial database should include a complete blood count, biochemical profile (including serum electrolytes), urinalysis, and abdominal radiographs (and abdominal ultrasound if available). Treatment and Control: Symptomatic therapy for acute vomiting includes fasting and withholding water for 24 hr to rest the GI tract. (Water can be provided in the form of ice.) Animals predisposed to hypovolemia, eg, animals with concurrent renal insufficiency or cardiac disease, should receive parenteral fluid therapy. Therapy for chronic vomiting is also directed to elimination of the primary cause and, in addition, to correction of dehydration, electrolyte imbalances, and acid-base disorders. The vomiting reflex should be suppressed. Vomiting associated with gastrointestinal obstruction commonly results in hypokalemia, hypochloremia, metabolic alkalosis, and paradoxical aciduria due to losses of secretions rich in potassium, chloride, and hydrogen. However, continued vomiting, lack of water intake, insensible water losses, and catabolism of body energy stores contribute to dehydration, poor tissue perfusion, hypoxia, and lactic acidosis. In the absence of gastric obstruction, the loss of bicarbonate from duodenal secretions may predispose to metabolic acidosis. Antiemetic therapy is indicated in animals with intractable vomiting, dehydration, and weakness. Commonly used antiemetics include antispasmodic medication, agents that depress the CTZ, drugs that suppress the emetic center, drugs that

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have peripheral activity, and the newer serotonin-antagonist agents. Drugs that act directly on the emetic center are very effective but tend to be less effective in the control of vomiting associated with severe GI disease. Antispasmodic agents (eg, scopolamine, 0.03 mg/kg, q.i.d., SC or IM) inhibit cholinergic activity from visceral receptors. Consequently, they may inhibit vomiting associated with excessive contraction of GI smooth muscle. These drugs are rarely effective in small animals. Drugs that depress the CTZ are used primarily to control motion sickness in people and may be useful to prevent nausea caused by drugs. They include dimenhydrinate (8 mg/kg, t.i.d., PO) and trimethobenzamide (3 mg/kg every 8-12 hr, IM). Trimethobenzamide is not as consistently effective as the phenothiazine antiemetic agents. Diphenhydramine (2-4 mg/kg, t.i.d., PO) an antihistamine, works by blocking H1 receptors in the vestibular apparatus and, to a lesser extent, the CTZ. It may be useful in management of motion sickness. Dopaminergic antagonists such as metoclopramide (0.2-0.5 mg/kg, q.i.d., PO or SC, or 1-2 mg/kg/day, slow IV or 1.3 µg/kg/min) and domperidone act at the level of the CTZ and peripheral receptors and are useful in the management of vomiting associated with toxins in the blood. Cisapride (0.1-0.5 mg/kg, t.i.d., PO) facilitates gastric emptying in dogs and cats and may be useful in the management of vomiting associated with delayed gastric emptying (as in gastritis, metabolic abnormalities, and postoperative gastric dilatation-volvulus). Ondansetron (0.5-1 mg/kg, every 12-24 hr, PO, or 0.5-1 mg/kg, 30 min before chemotherapy, PO) is a potent new antiemetic agent. It is a selective serotonin-receptor antagonist with both central and peripheral activity. It should be considered in cases unresponsive to other antiemetic agents but is quite expensive.

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Endocrine System Hormone synthesized in excess of the body's requirement is degraded by fusion of the hormone-containing granules with lysosomes—a process termed crinophagy. Steroid hormones have a long half-life in blood (typically measured in hours) and bind reversibly to high-affinity, specific binding proteins in plasma. They are lipid soluble and, therefore, move readily through the cell membrane; their primary site of action is the nucleus of target cells. Catecholamines share similar mechanisms of action with polypeptide hormones, whereas the characteristics of iodothyronines more closely resemble those of steroid hormones. Proliferative Lesions in Endocrine Glands The most significant alteration of endocrine glands in animals that results in clinical disease is the development of proliferative lesions (eg, hyperplasia, benign and malignant neoplasia). Mechanisms of Endocrine Disease Many diseases of the endocrine system are characterized by dramatic functional disturbances and characteristic clinicopathologic alterations that affect one or several body systems. These changes may involve primarily the skin (eg, hair loss caused by hypothyroidism and hypercortisolism), nervous system (eg, seizures caused by hyperinsulinism), urinary system (eg, polyuria caused by diabetes mellitus, diabetes insipidus, or hypercortisolism), or skeletal system (eg, fractures induced by hyperparathyroidism). Hyperadrenocorticism (Cushing's disease, Cortisol excess) Hyperadrenocorticism may be the most frequent endocrinopathy in adult to aged dogs but is infrequent in other domestic animals. The clinical signs and lesions associated with hyperadrenocorticism result primarily from chronic excess of cortisol. The disease is insidious and slowly progressive. (See also The Pituitary Gland : Introduction .) Etiology and Pathogenesis: Increased cortisol levels in dogs may result from one of several pathogenic mechanisms. The most common is an adenoma or hyperplasia of the adrenocorticotropic hormone (ACTH)-containing cells of the pituitary gland (pars distalis or pars intermedia), which results in bilateral adrenal cortical hypertrophy and hyperplasia. This form of the disease is referred to as pituitary-dependent hyperadrenocorticism and occurs in ~90% of cases. Functional adrenal tumors are a far less frequent cause of hyperadrenocorticism in dogs. Clinical Findings and Lesions: Polyuria, polydipsia (PU/PD), and polyphagia are among the most common clinical signs. They occur either as a direct result of the hypercortisolism or secondary to compression or invasion of the hypothalamus by a pituitary macroadenoma. The muscles of the extremities and abdomen weaken and atrophy, with gradual abdominal enlargement, lordosis, muscle trembling, and weakness. Hepatomegaly due to increased fat and glycogen deposition may contribute to the distended, often pendulous, abdomen. The muscular asthenia and wasting is the result of increased catabolism combined with diminished protein synthesis. Alopecia is symmetrical and may involve a significant portion of the body surface. There is atrophy of the epidermis and pilosebaceous apparatus, combined with loss of collagen and elastin in the dermis and subcutis. Cutaneous mineralization is a characteristic although infrequent finding in dogs. Although mineral deposition may occur anywhere in the skin, the dorsal midline, ventral abdomen, and inguinal region are affected most frequently. The mineral deposits occur despite normal blood calcium and phosphorus levels probably because of the gluconeogenic and protein catabolic actions of cortisol. Mineralization may also occur in other tissues of the body, most frequently the airways and blood vessels. Behavioral problems occur frequently in both dogs and people with hyperadrenocorticism. Signs in dogs include lethargy, sleep-wake cycle disturbances, panting, and decreased interaction with owners (which may be characterized as decreased responsiveness to attention or diminished enthusiasm of greeting behavior). Adenomas of the adrenal cortex are seen most frequently in old dogs and sporadically in horses, cattle, and sheep. Carcinomas of the adrenal cortex occur less frequently than adenomas and have been reported most often in adult to older cattle and dogs, with no apparent breed or sex predilection. Adrenal carcinomas are larger then adenomas and more likely to be bilateral. Diagnosis: A complete blood count generally reveals a stress leukogram (mature neutrophilia, lymphopenia, eosinopenia). In dogs, serum concentrations of sodium, potassium, and chloride are usually normal. Cortisol excess stimulates the synthesis and release of a steroid-inducible isoenzyme (ciALP) of alkaline phosphatase, and increased levels of alkaline phosphatase are seen in 80% of dogs. Blood glucose is moderately increased and, occasionally, marked hyperglycemia develops. Diabetes

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mellitus occurs in 5-10% of cases. The serum concentration of cholesterol may be increased to 250-400 mg/dL. A consistent finding is the excretion of large volumes of dilute urine with a low specific gravity (≤1.015). A definitive diagnosis requires specific adrenal function tests. Currently, three tests are available that can be used to diagnose hyperadrenocorticism: the urine cortisol/creatinine ratio (UCCR), the ACTH stimulation test, and the low-dose dexamethasone suppression test (LDDS). The UCCR is a rapid and easy screening test; however, it is very sensitive and can be associated with false positive results. Therefore, a normal UCCR can only effectively rule out the diagnosis of hyperadrenocorticism, whereas an increased UCCR requires an LDDS test to confirm the diagnosis. The ACTH stimulation test will correctly identify ~80-85% of dogs with hyperadrenocorticism. The test takes only 1 or 2 hr, depending on the protocol used, and requires obtaining two serum samples for determination of cortisol levels. Dogs with hyperadrenocorticism usually have an exaggerated response to exogenously administered ACTH; however, 15-20% of dogs have a normal response, and further tests may be required if the history and clinical signs are strongly suggestive of hyperadrenocorticism. As is true of the UCCR, severe nonadrenal illness (eg, diabetes mellitus) may result in an exaggerated response to ACTH in the absence of hyperadrenocorticism. In animals with diabetes in which the diagnosis of hyperadrenocorticism is suspected, use of the LDDS test may be preferred. In the LDDS test, exogenously administered dexamethasone will suppress ACTH and cortisol levels for 8 hr in normal dogs. In dogs with hyperadrenocorticism, either the negative feedback mechanisms are lost (pituitary-dependent hyperadrenocorticism) or the adrenal(s) autonomously produces excessive levels of cortisol (adrenal tumors). In either case, cortisol levels fail to suppress normally in response to the dexamethasone. The LDDS test identifies ~95% of animals with hyperadrenocorticism. Results can be normal in the early stages of the disease when cortisol secretion is increased and negative feedback mechanisms are still intact. In this case, the animals should be monitored closely for signs of disease progression; retesting will be required to confirm the diagnosis. Measurement of ciALP as a screening test appears to lack both sensitivity and specificity. An increased ciALP is suggestive but not diagnostic. Once hyperadrenocorticism has been diagnosed, it is necessary to distinguish between pituitary-dependent hyperadrenocorticism (PDH) and adrenal tumors to give a prognosis and to help in deciding on treatment options. Dogs with PDH that is well controlled can be expected to live ~24 mo after diagnosis. PDH accounts for ~90% of the cases of hyperadrenocorticism. Dogs with adrenocortical adenomas undergoing successful therapy (medical or surgical) should have a life expectancy similar to that of dogs with PDH. About 50% of adrenal tumors in dogs are carcinomas, for which the prognosis is grave. Two tests are used to distinguish PDH from adrenal tumors. The first is the high-dose dexamethasone suppression test (HDDS), in which cortisol levels are determined before and 8 hr after administration of a dose of dexamethasone (10 times the dose in the LDDS). However, interpretation of results varies; some laboratories consider >50% suppression of the cortisol level to be diagnostic for PDH, while others use an absolute number (eg, <1 µg/dL, 28 nmol/L) to distinguish PDH from adrenal tumors. In dogs with PDH, ~70% show suppression of cortisol levels on the HDDS; however, ~30% do not suppress. This may reflect the percentage of dogs that have PDH as the result of hyperplasia or an adenoma in the pars intermedia. Because the pars intermedia does not have a portal blood supply, it does not recognize the dexamethasone. Cortisol levels in dogs with adrenal tumors do not suppress because the adrenal(s) is functioning autonomously. Therefore, when interpreting the HDDS, suppression of cortisol levels is diagnostic for PDH, while nonsuppression may occur with PDH or adrenal tumors (in which case, additional tests are in order [imaging or plasma ACTH concentrations]). Plasma levels of ACTH can reliably distinguish between PDH and adrenal tumors, although multiple samples may be required. In dogs with PDH, ACTH levels are normal or increased despite hypercortisolemia, while in dogs with tumors, ACTH levels are low to nondetectable due to feedback inhibition by cortisol. Measurement of plasma ACTH levels is an excellent test to distinguish PDH from adrenal tumors but can be difficult in a private practice due to sample handling, collection constraints, and the essential consultation with the laboratory before sample collection. Treatment: Dogs with hyperadrenocorticism that has been confirmed by laboratory testing can be treated medically or surgically. Dogs with PDH can be managed medically by oral administration of mitotane (o,p'-DDD), initially at 25-50 mg/kg/day for 7-10 days. Clinical signs such as PU/PD are closely monitored; if water consumption, appetite, or activity level decreases, or if adverse reactions (eg, vomiting, diarrhea) are noted, the medication should be discontinued. In ~80% of dogs, gradually increasing doses of the drug are required to maintain adequate clinical remission. Thus, dogs should be closely monitored during therapy. The use of ACTH stimulation testing is required to determine the efficacy of therapy and to monitor for toxicity. In dogs treated with mitotane, clinical signs of hyperadrenocorticism are reversed rapidly. Initially, water consumption, frequency of urination, and appetite are reduced. Muscle strength and physical activity increase within a few weeks, and substantial hair regrowth usually occurs in 2-5 mo. The levels of plasma cortisol decline progressively. The exaggerated increase in plasma corticosteroids in response to ACTH stimulation is eliminated. The maintenance dose of mitotane must be continued for the life of the dog to prevent recurrence of clinical signs.
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Side effects of mitotane at the recommended dose include GI irritation (vomiting and anorexia), CNS disturbances (ataxia, weakness, seizures), mild hypoglycemia, and a moderate increase in serum alkaline phosphatase. Dosages of mitotane that are effectively cytotoxic to hyperplastic adrenocortices may not destroy functional adrenocortical adenomas and carcinomas in dogs. Higher dose levels are often required to attain remission of clinical signs. In addition to mitotane, ketoconazole and l-deprenyl have been effective in the management of PDH in dogs, and ldeprenyl has recently been approved by the FDA for this use. It is effective in ~80% of cases and is associated with few side effects. Its mechanism of action is monoamine oxidase inhibitor. When there is evidence of an adrenal tumor, the recommended treatment is removal of the affected gland. Hypoadrenocorticism (Addison's disease) A deficiency in adrenocortical hormones is seen most commonly in young to middle-aged dogs and occasionally in horses. The disease may be familial in Standard Poodles. The cause of primary adrenocortical failure usually is not known, although most cases probably result from an autoimmune process. Other causes can be destruction of the adrenal gland by granulomatous disease, metastatic tumor, hemorrhage, infarction, or overdose of mitotane. Clinical Findings: Although hypoadrenocorticism occurs in dogs of any breed, sex, or age, idiopathic adrenocortical insufficiency is most common in young female adults. This may be related to its suspected immune-mediated pathogenesis. A reduction in secretion of aldosterone, the principal mineralocorticoid, results in marked alterations of serum levels of potassium, sodium, and chloride. Potassium excretion by the kidneys is reduced and results in a progressive rise in serum potassium levels. Hyponatremia and hypochloremia result from renal tubular loss. Severe hyperkalemia may result in bradycardia and an irregular heart rate with alterations in the ECG. Some dogs develop a pronounced bradycardia (heart rate ≤50 beats/min) that predisposes to weakness or circulatory collapse after minimal exertion. Although the development of clinical signs often is not readily apparent, acute circulatory collapse and evidence of renal failure frequently occur. A progressive decrease in blood volume contributes to hypotension, weakness, and microcardia. Increased excretion of water by the kidneys, due to decreased reabsorption of sodium and chloride, results in progressive dehydration and hemoconcentration. Emesis, diarrhea, and anorexia are common and contribute to the animal's deterioration. Weight loss is frequently severe. Similar clinical signs are seen in cats with hypoadrenocorticism. Decreased production of glucocorticoids results in several characteristic functional disturbances. Decreased gluconeogenesis and increased sensitivity to insulin contribute to the development of moderate hypoglycemia. In some dogs, hyperpigmentation of the skin occurs due to the lack of negative feedback on the pituitary gland and increased release. The plasma cortisol levels are below the resting reference range, and there is little or no increase in blood cortisol levels after ACTH administration. Lesions: The most common lesion in dogs is bilateral idiopathic adrenocortical atrophy, in which all layers of the cortex are markedly reduced in thickness. All three zones of the adrenal cortex are involved, including the zona glomerulosa which is not under ACTH control; however, no obvious pituitary lesions have been seen in dogs with idiopathic adrenal cortical atrophy. A destructive pituitary lesion that decreases ACTH secretion is characterized by severe atrophy of the inner two cortical zones of the adrenal gland; the zona glomerulosa remains intact. Diagnosis: A presumptive diagnosis is based on the history and supportive (although not specific) laboratory abnormalities, including hyponatremia, hyperkalemia, a sodium:potassium ratio of <25:1, azotemia, mild acidosis, and a normocytic normochromic anemia. Severe GI blood loss has also been reported. Occasionally, mild hypoglycemia is present. The hyperkalemia results in ECG changes: an elevation (spiking) of the T wave, a flattening or absence of the P wave, a prolonged PR interval, and a widening of the QRS complex. Ventricular fibrillation or asystole may occur with potassium levels >11 mEq/L. Differential diagnoses include primary GI disease (especially whipworm infection), renal failure, acute pancreatitis, and toxin ingestion. For definitive diagnosis, evaluation of adrenal function is required. After obtaining a baseline blood sample, ACTH (gel or synthetic) is administered IM and a second blood sample obtained 1-2 hr later. Affected dogs have low baseline cortisol levels, and there is little response to ACTH administration. This test can be completed in most animals before replacement hormone therapy is started. Treatment: An adrenal crisis is an acute medical emergency. An IV catheter should be inserted and a 0.9% saline infusion begun. If the dog is hypoglycemic, the saline can include 5% dextrose. Prednisolone sodium succinate (22-30 mg/kg) or dexamethasone sodium phosphate (2.2-4.4 mg/kg) may be used in the initial management of shock.

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In cases of severe nonresponsive hyperkalemia, 10% glucose (4.4-11 mL/kg) in 0.9% saline can be given over 30-60 min to increase potassium movement into the cells. Regular insulin (0.28-1.1 u/kg) administered IM will enhance glucose and potassium uptake, but 10% glucose (20 mL per unit of insulin) should be administered IV concurrently to avoid hypoglycemia. Sodium may be added to the diet (1-5 g/day) if hyponatremia persists despite a normal serum potassium concentration. Treatment of horses with hypoadrenocorticism is similar—aggressive replacement of fluids, steroids, and glucose if needed in an adrenal crisis. Supportive therapy and rest are indicated in cases of chronic Addison's disease. The Pancreas: Introduction Pancreatic islets contain α, β, and δ cells, each of which synthesize a unique polypeptide hormone. β Cells account for 60-70% of the islet-cell population and secrete insulin, α cells secrete glucagon, and δ cells secrete somatostatin. The pancreatic islets function as discrete microendocrine organs. In some species, the β cells are located in a relatively homogeneous central mass, the α cells are located primarily at the periphery of the islet in an external mantle, and the δ cells are interspersed between the outer layer of α cells and inner core of β cells. Afferent vessels and nerves enter the islet in this peripheral tricellular region. The close anatomic relationship of α, β, and δ cells in this heterogeneous cortical region allow it to function as a local glucose sensor, permitting a coordinated output of insulin and glucagon in response to fluctuations in blood glucose. The major physiologic stimulus for the release of insulin from β cells is an increase in the concentration of glucose in the extracellular fluid. Specific glucoreceptors that bind with glucose exist on the plasma membrane of β cells. An appropriate level of extracellular calcium is required for insulin secretion. In certain hypocalcemic disorders (eg, parturient hypocalcemia in cows), insulin secretion may be inhibited, owing to the low extracellular fluid calcium concentration, and result in hyperglycemia. Tissues that are especially responsive to insulin include skeletal and cardiac muscle, adipose tissue, fibroblasts, liver, WBC, mammary glands, cartilage, bone, skin, aorta, pituitary gland, and peripheral nerves. The main function of insulin is to stimulate anabolic reactions involving carbohydrates, fats, proteins, and nucleic acids. Liver, adipose cells, and muscle are three principal target sites for insulin. Insulin catalyzes the formation of macromolecules used in cell structure and energy stores, and it regulates many cell functions. In general, insulin increases the transfer of glucose and certain other monosaccharides, some amino acids and fatty acids, and potassium and magnesium ions across the plasma membrane of target cells. It also decreases the rate of lipolysis, proteolysis, ketogenesis, and gluconeogenesis. Glucagon is secreted in response to a reduction in blood glucose. It promotes mobilization of stores of energy-yielding nutrients by increasing glycogenolysis, gluconeogenesis, and lipolysis. Diabetes Mellitus Diabetes mellitus is a chronic disorder of carbohydrate metabolism due to relative or absolute insulin deficiency. In dogs, females are affected twice as often as males. Etiology and Pathogenesis: The pathogenic mechanisms responsible for decreased insulin production and secretion are multiple, but usually they are related to destruction of islet cells, secondary to either severe pancreatitis or selective degeneration. In dogs, chronic pancreatitis and immune destruction of the pancreatic islets are the most common causes of diabetes mellitus. Chronic relapsing pancreatitis with progressive loss of both exocrine and endocrine cells and their replacement by fibrous connective tissue results in diabetes mellitus. Selective infiltration of islets with amyloid, glycogen, and collagen with destruction of islet cells are less frequent causes of diabetes mellitus in dogs than in cats. In other cases, the numbers of β cells are decreased, and the cells become vacuolated; in chronic cases, the islets are difficult to find. Insulin resistance and secondary diabetes mellitus are also seen in many dogs with hyperadrenocorticism, and chronic administration of glucocorticoids or progestins can predispose to diabetes mellitus. In dogs, but not cats, progesterone leads to release of growth hormone, resulting in hyperglycemia and insulin resistance. Obesity also predisposes to insulin resistance in both dogs and cats. Cats with diabetes mellitus usually have specific degenerative lesions localized selectively in the islets of Langerhans, whereas the remainder of the pancreas appears to be normal. The selective deposition of amyloid in islets, with degenerative changes in α and β cells, is the most common pancreatic lesion in many cats with diabetes. The amyloid appears to arise from islet-associated polypeptide (IAPP), which is secreted together with insulin from the β cell. Cats (and 20% of people with type II diabetes) seem unable to process IAPP normally, which leads to excessive accumulation and conversion into amyloid. As cats age, a greater percentage of their islets contain amyloid. Cats with diabetes have a greater percentage of their islets affected with larger amounts of amyloid than age-matched cats without diabetes. The amyloid or IAPP (or both) lead to both physical disruption of the β cell and insulin resistance, resulting in diabetes. Infection with certain viruses may cause selective islet damage or pancreatitis and has been suggested to be responsible for certain cases of rapidly developing diabetes mellitus. Clinical Findings:

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Common signs in dogs include polydipsia, polyuria, polyphagia with weight loss, bilateral cataracts, and weakness. The renal threshold for glucose is ~180 mg/dL in dogs and ~240 mg/dL in cats. Diabetic animals have decreased resistance to bacterial and fungal infections and often develop chronic or recurrent infections, such as cystitis, prostatitis, bronchopneumonia, and dermatitis. Radiographic evidence of emphysematous cystitis (rare) is suggestive of diabetes mellitus because of infections with glucose-fermenting organisms such as Proteus sp , Aerobacter aerogenes , and Escherichia coli , which result in gas formation in the wall and lumen of the bladder. Emphysema also may develop in the wall of the gallbladder in diabetic dogs. Hepatomegaly due to lipid accumulation is common in diabetic dogs and cats. Cataracts develop frequently in dogs (not cats) with poorly controlled diabetes mellitus. Cataract formation in dogs is related to the unique sorbitol pathway by which glucose is metabolized in the lens, which leads to edema of the lens and disruption of normal light transmission. Diagnosis: The normal fasting value for blood glucose in dogs and cats is 75-120 mg/dL. Treatment: Long-term success depends on the understanding and cooperation of the owner. Treatment involves a combination of weight reduction, diet (high fiber, high complex carbohydrate), and insulin. Intact females should be neutered. If diet and weight reduction do not control the disease, either ultralente, NPH, or lente insulin should be given, adjusting the dose until the disease is brought under control and the urine only intermittently contains traces of sugar. Recently, the use of oral hypoglycemia agents (glipizide) has been evaluated in diabetic cats. Glipizide is a sulfonylurea that stimulates the release of insulin from functional β cells. Glipizide should not be used in thin or ketonuric cats when absolute insulin deficiency is likely and exogenous insulin administration is required. Glipizide is contraindicated in dogs. Ketoacidosis is a serious complication of diabetes mellitus and should be regarded as a medical emergency. Functional Islet Cell Tumors The most frequent pancreatic islet tumor is an islet cell carcinoma derived from insulin-secreting β cells. These neoplasms frequently are hormonally active and secrete excessive amounts of insulin, which causes hypoglycemia. Clinical Findings: The clinical signs seen with insulinomas result from excessive insulin secretion, which leads to an increased rate of transfer of glucose from the extracellular fluid to body tissues, and thus to severe hypoglycemia. The clinical signs are a reflection of the hypoglycemia and are not specific for hyperinsulinism associated with β-cell neoplasms. Initial signs include posterior weakness, fatigue after exercise, generalized muscular twitching and weakness, ataxia, mental confusion, and changes of temperament. Dogs are easily agitated, and there are intermittent periods of excitability and restlessness. The predominance of clinical signs relating to the CNS demonstrates the primary dependence of the brain on the metabolism of glucose for energy. When the brain is not supplied with glucose, cerebral oxidation decreases and manifestations of anoxia appear. Because clinical signs are compatible with primary disease of the CNS, functional islet cell tumors may be misdiagnosed as idiopathic epilepsy, brain tumors, or other organic neurologic disease. Repeated episodes of prolonged and severe hypoglycemia may result in irreversible neuronal degeneration throughout the brain. Diagnosis: A blood glucose determination should be done on all older dogs with a history of periodic weakness, collapse, or seizures. Differential diagnoses for hypoglycemia include hypoadrenocorticism, hepatic failure, large extrapancreatic neoplasms, sepsis, polycythemia, insulin overdosage, and laboratory error. Treatment: Complete excision of the tumor ameliorates the hypoglycemia and associated neurologic signs, unless there have been irreversible changes in the CNS or there are nonvisible metastases and hypoglycemia persists after surgery. Dogs with inoperable tumors may be managed fairly well with multiple feedings/day and glucocorticoid administration (0.5-1 mg/kg/day). Diazoxide (20-80 mg/kg/day, t.i.d.) may also alleviate clinical signs in some dogs. Gastrin-secreting Islet Cell Tumors Gastrinomas of the pancreas have been reported in man, dogs, and a cat. Hypersecretion of gastrin in man results in the Zollinger-Ellison syndrome, consisting of hypersecretion of gastric acid and recurrent peptic ulceration in the GI tract. The tumors, derived from ectopic amine precursor uptake decarboxylase (APUD) cells in the pancreas, produce an excess of the hormone gastrin, which normally is secreted by cells of the antral and duodenal mucosa. Diagnosis: Serum gastrin levels have been evaluated in a limited number of dogs with gastrinomas. Treatment: Excision of the gastrin-secreting mass in the pancreas can be attempted. Medical management with H2-receptor antagonists (cimetidine or ranitidine) or the proton-pump inhibitor omeprazole may temporarily alleviate clinical signs in animals with inoperable disease.
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Hypercalcemia In Dogs And Cats: Overview Total serum calcium concentrations of ≤15 mg/dL may not be associated with systemic signs, but serum concentrations of >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.
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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.
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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:
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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 <60 mL/kg/day (dogs). After 7-10 days of therapy with mitotane or a reduction in water consumption to <60 mL/kg/day, an ACTH response test should be performed to determine if adequate cortisol suppression has occurred. The pre-ACTH and post-ACTH cortisols should both be in the normal range. Alternative therapies for hyperadrenocorticism in dogs include the use of ketoconazole, which affects steroid biosynthesis. Surgical removal of unilateral adrenal adenomas or adenocarcinomas may be indicated in some cases; however, surgical and anesthetic complications (eg, hypotension) may develop secondary to hypoadrenocorticism, which occurs immediately after surgical removal of the tumor. Medical treatment of adrenal tumors is difficult because they tend to be resistant to the effects of mitotane. Finally, if the dog is showing neurologic signs (such as anorexia, stupor, or seizures) and a large pituitary tumor (macroadenoma) is identified, radiation therapy of the pituitary gland is indicated. Diabetes Insipidus When target cells in the kidney lack the biochemical machinery necessary to respond to the secretion of normal or increased circulating levels of ADH, nephrogenic diabetes insipidus results. Etiology: The hypophyseal form of central diabetes insipidus develops as a result of compression and destruction of the pars nervosa, infundibular stalk, or supraoptic nucleus in the hypothalamus. The lesions responsible for the disruption of ADH synthesis or secretion in hypophyseal diabetes insipidus include large pituitary neoplasms (endocrinologically active or inactive), a dorsally expanding cyst or inflammatory granuloma, and traumatic injury to the skull with hemorrhage and glial proliferation in the neurohypophyseal system. Clinical Findings and Lesions: Affected animals excrete large volumes of hypotonic urine and drink equally large amounts of water. Diagnosis: This is based on chronic polyuria that does not respond to dehydration and is not due to primary renal disease. To evaluate the ability to concentrate urine, a water deprivation test should be done if the animal is not dehydrated and does not have renal disease. The bladder is emptied, and water and food are withheld (usually 3-8 hr) to provide a maximum stimulus for ADH secretion. The animal should be monitored carefully to prevent a loss of >5% body wt and severe dehydration. Urine and plasma osmolality should be determined; however, because these tests are not readily available to most practitioners, urine specific gravity is frequently used instead. At the end of the test, urine specific gravity is >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 <1.8 in those with severe deficiency. The ratio of urine osmolality after ADH administration as compared with water deprivation is >2 in animals with primary ADH deficiency, between 1.1 and 2 in those with inhibitors to ADH action, and <1.1 in those unresponsive to ADH. Diabetes insipidus also needs to be distinguished from other diseases with polyuria. The most common are diabetes mellitus with glycosuria and high urine specific gravity, and chronic nephritis with a urine specific gravity that is usually low and shows evidence of renal failure (protein, casts, etc). Treatment: Polyuria may be controlled using desmopressin acetate, a synthetic analog of ADH. Feline Acromegaly Acromegaly, or hypersomatotropism, results from chronic, excessive secretion of growth hormone in the adult animal. Acromegaly in cats is caused by a growth-hormone-secreting tumor of the anterior pituitary. In cats, these tumors grow slowly and may be present for a long time before clinical signs appear. Clinical Findings: Feline acromegaly occurs in older (8-14 yr) cats, and there appears to be a sex predilection for males. Clinical signs of uncontrolled diabetes mellitus are often seen as the first sign of acromegaly in cats; therefore, polydipsia, polyuria, and polyphagia are the most common presenting signs. Net weight gain of lean body mass in cats suffering from uncontrolled diabetes mellitus is a key sign of acromegaly. Organomegaly including renomegaly, hepatomegaly, and enlargement of endocrine organs is also seen. Some cats show the classic enlargement of extremities, body size, jaw, tongue, and forehead that is characteristic of acromegaly in man. Some of the most striking manifestations occur in the musculoskeletal system
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and include an increase in muscle mass, and growth of the acral segments of the body including the paws, chin, and skull. Cardiovascular abnormalities such as cardiomegaly (radiographic and echocardiographic), systolic murmurs, and congestive heart failure develop late in the course of the disease. Impaired glucose tolerance and insulin resistance resulting in diabetes mellitus are seen in all cats with acromegaly. Measurement of endogenous insulin reveals dramatically increased serum insulin concentrations. Despite severe insulin resistance and hyperglycemia, ketosis is rare. Feline acromegaly should be suspected in any diabetic cat that has severe insulin resistance (insulin requirement >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 µg/dL, <10 nmol/L) and rarely increases more than 0.2 µg/dL (2.5 nmol/L) above the baseline value. With TSH stimulation testing, primary hypothyroidism can be distinguished from other causes of depression of basal serum T4 concentrations (eg, drugs and nonthyroidal illness), in which the serum T4 response may be suppressed but the slope of the increase is similar to that of normal. To rule out a diagnosis of hypothyroidism, the post-TSH serum T4 concentration should generally either increase by at least 2 mg/dL (25 nmol/L) over the basal serum T4 value or exceed the normal range of basal T4 concentrations by 6 hr after TSH injection. Dogs that fail to meet these criteria can be considered to have hypothyroidism, and their response to thyroid hormone replacement therapy should be evaluated.

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Unfortunately, because of limited availability of TSH and its high cost, the TSH stimulation test has fallen out of favor with many practicing veterinarians. A serum concentration (determined by dialysis) of free T4 as a confirmatory test for hypothyroidism appears to be a reasonable alternative. Free T4 is the fraction of T4 that is not bound to plasma proteins. Because the concentration of free T4 reflects the hormone available for entry into cells, measurement of free T4 provides a more consistent assessment of thyroid status at the tissue level than does measurement of total T4. Treatment: Thyroxine (T4) is the thyroid hormone replacement compound of choice in dogs. With few exceptions, replacement therapy is necessary for the remainder of the dog's life; careful initial diagnosis and tailoring of treatment is essential. Non-neoplastic Enlargement of the Thyroid Gland (Goiter) Non-neoplastic and noninflammatory enlargements of the thyroid gland develop in all domestic mammals as well as birds. The major causes of goiter include iodine deficiency, goitrogenic substances, dietary iodine excess, and inherited enzyme defects in the biosynthesis of thyroid hormones. Iodine Deficiency: Iodine deficiency is responsible for most goiters seen in large domestic animals. Insufficient iodine reduces the ability of the thyroid to make thyroid hormone. With reduced circulating thyroid hormone, the pituitary secretes more thyroid-stimulating hormone (TSH), which acts as a stimulus for hyperplasia of the thyroid gland and goiter. The hyperplastic gland may, and usually does, compensate for the reduced availability of iodine; therefore, goiter is in no way synonymous with hypothyroidism. However, animals born to dams on iodine-deficient diets are more likely to develop severe thyroid enlargement and have clinical signs of hypothyroidism. Goiter caused by iodine deficiency is most common in newborn pigs, lambs, calves, and foals in iodine-deficient areas. The neck is usually grossly enlarged, and the skin and other tissue may be thickened, flabby, and edematous. In mildly affected animals, treatment with iodized salt (containing >0.007% iodine) may resolve the goiter and associated clinical signs, but many die before or soon after birth. Prevention is more effective than treatment. The use of stabilized iodized salt is recommended in all areas known or suspected to be iodine deficient. Goitrogenic Substances: Certain plants may produce goiter when ingested in sufficient amounts, especially in the absence of adequate iodine intake. Soy beans are most notable, but cabbage, rape, kale, and turnips all contain less potent goitrogens. Cooking or heating (and the usual processing of soybean meal) destroys the goitrogenic substance in these plants. All of the goitrogenic substances act by interfering with production of thyroid hormone. As with iodine deficiency, the pituitary responds to the reduced circulating thyroid hormone levels by increasing its secretion of TSH, which results in thyroid gland enlargement. The disease is usually not significant in adult animals, but severe thyroid enlargement and hypothyroidism may develop in newborns. Iodine Toxicity: Foals of dams fed excess iodine may develop extreme thyroid enlargement and die before birth or shortly thereafter. Clinical signs may include general weakness, long hair, and marked limb abnormalities. Hyperthyroidism Excessive secretion of the thyroid hormones, T4 and T3, results in signs that reflect an increased metabolic rate and produces clinical hyperthyroidism. It is most common in middle-aged to old cats but also develops rarely in dogs. Functional thyroid adenoma (adenomatous hyperplasia) is the most common cause of feline hyperthyroidism; in ~70% of cases, both thyroid lobes are enlarged. Thyroid carcinoma, the primary cause of hyperthyroidism in dogs, is rare in cats (1-2% of hyperthyroidism cases). Clinical Findings and Diagnosis: The most common signs include weight loss, increased appetite, hyperexcitability, polydipsia, polyuria, and palpable enlargement of the thyroid gland. GI signs are also common and may include vomiting, diarrhea, and increased volume of feces. Cardiovascular signs include tachycardia, systolic murmurs, dyspnea, cardiomegaly, and congestive heart failure. Of hyperthyroid cats, 5-10% exhibit apathetic signs (eg, anorexia, lethargy, and depression); weight loss is common. High serum concentrations of T4 and T3 confirm the diagnosis; however, they are subject to a wide degree of fluctuation, and more than one basal measurement may be necessary. Treatment: Spontaneous hyperthyroidism can be treated by thyroidectomy, radioiodine therapy, or chronic administration of an antithyroid drug. With unilateral thyroid tumors, hemithyroidectomy corrects the hyperthyroid state, and thyroxine supplementation usually is not necessary. For bilateral thyroid tumors, complete thyroidectomy is indicated, but parathyroid function must be preserved to avoid postoperative hypocalcemia. Thyroxine supplementation should be started 1-2 days after complete thyroidectomy.
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Radioactive iodine provides a simple and safe treatment. Radioiodine is concentrated within the thyroid gland and selectively irradiates and destroys hyperfunctioning thyroid tissue. The main disadvantage of such therapy is that most practitioners do not have access to radioiodine. Treatment with methimazole, an antithyroid drug, controls hyperthyroidism by blocking thyroid hormone synthesis. Adverse side effects, the more serious of which are agranulocytosis and thrombocytopenia, develop in <5% of treated cats. If this occurs, methimazole should be discontinued and supportive therapy instituted; these adverse reactions should resolve within 2 wk. Propylthiouracil, another antithyroid drug, is not recommended for use in cats because of the high incidence of serious side effects (especially hemolytic anemia and thrombocytopenia).

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Eye and Ear Eyelid Disorders Entropion is an inversion of all or part of the lid margins that may involve one or both eyelids and the canthi. Inversion of the cilia (or eyelashes) or facial hairs causes further discomfort, conjunctival and corneal irritation, and if protracted, corneal scarring, pigmentation, and possibly ulceration. Established entropion may require surgical correction with the Hotz-Celsus procedure or its modifications. Ectropion is a slack, everted lid margin, usually with a large palpebral fissure. It is a common bilateral conformational abnormality in a number of dog breeds. Contracting scars in the lid or facial nerve paralysis may produce unilateral ectropion in any species. Conjunctival exposure to environmental irritants and secondary bacterial infection can result in chronic or recurrent conjunctivitis. Topical antibiotic-corticosteroid preparations may temporarily control intermittent infections, but surgical lid-shortening procedures are often indicated. Mild cases can be controlled by repeated, periodic lavage with mild decongestant solutions. Lagophthalmos is an inability to fully close the lids and protect the cornea from drying and trauma. Inflammation Blepharitis (inflammation of the eyelids) can result from extension of a generalized dermatitis, conjunctivitis or local infections, or irritants such as plant oils or solar exposure. The mucocutaneous junction of the skin and conjunctiva can be the site of lesions of immune-mediated diseases such as pemphigus. In generalized blepharitis, systemic therapy often is indicated in addition to topical treatment. Supportive therapy of hot packing and frequent cleansing often is indicated in acute cases. Nonophthalmic preparations can be used to treat the eyelids, but caution in application is indicated to avoid corneal contact and possible irritation. Keratoconjunctivitis sicca (KCS) is due to an aqueous tear deficiency and usually results in persistent, mucopurulent conjunctivitis and corneal ulceration and scarring. KCS occurs in dogs, cats, and horses. In dogs, it is often associated with an autoimmune dacryoadenitis of both the lacrimal and nictitans glands. Distemper infection, chronic sulfonamide therapy, and trauma are less frequent causes of KCS in dogs. KCS occurs infrequently in cats and has been associated with chronic feline herpesvirus infections. In horses, KCS may follow head trauma. Lacrimogenics such as topical cyclosporin A (1-2%, b.i.d.) may increase tear production in some dogs. Ophthalmic pilocarpine mixed in food may be useful (a 20-30 lb [10-15 kg] dog should be started on 2-4 drops of 2% pilocarpine, b.i.d.). Mucolytic agents (eg, 10% acetylcysteine) lyse excess mucus and restore the spreading ability of other topical agents. Conjunctiva Subconjunctival hemorrhage may arise from trauma or blood dyscrasias and certain infectious diseases. Chemosis, or conjunctival edema, occurs to some degree with all cases of conjunctivitis, but the most dramatic examples are seen with trauma, hypoproteinemia, allergic reactions, and insect bites. The latter are treated with topical corticosteroids and usually resolve rapidly. Conjunctivitis is common in all domestic species. The etiologic agent(s) may vary from infectious to environmental irritants. The signs are hyperemia, chemosis, ocular discharge, follicular hyperplasia, and mild ocular discomfort. In cats, herpesvirus, Mycoplasma , or Chlamydia psittaci may produce conjunctivitis that begins in one eye and becomes bilateral after ~1 wk. Specific diagnosis is made most rapidly by demonstrating the inclusions or the agent in conjunctival scrapings. Bilateral conjunctivitis is common in a variety of viral infections in all species. Herpesviruses produce conjunctivitis in cats, cattle, horses, and pigs. Purulent discharge indicates a bacterial component, but this may be opportunistic due to debilitation of the mucous membrane. Environmental irritants and allergens are common causes of conjunctivitis in all species. If a mucopurulent exudate is present, topical antibiotic therapy is indicated but may not be curative if other predisposing factors are involved. Topical tetracycline is indicated for chlamydial and mycoplasmal infections; topical antiviral preparations (eg, idoxuridine) are indicated for herpesvirus infections when both the cornea and conjunctiva are involved. Ulcerative keratitis may be superficial, deep, deep with descemetocele, or perforating. Pain, corneal irregularity, edema, and eventually vascularization are signs of ulceration. A dense, white infiltrate at the ulcer margin indicates strong leukotaxis and bacterial involvement. To detect small ulcers, topical fluorescein may be required. In dogs and horses, most ulcers are mechanical in origin; in cattle, sheep, and reindeer, infectious agents and mechanical causes are important; in cats and horses, herpesvirus infection is a frequent cause. All ulcers have the potential for secondary bacterial contamination or endogenous enzymatic “melting” of the stroma. Therapy for superficial ulcers is usually medical and consists of topical antibiotic(s), topical atropine for iridocycloplegia, and correction of any mechanical factors.

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Glaucoma The glaucomas in animals represent a group of diseases characterized by increased intraocular pressure with resultant retinal and optic disk destruction. In cats, the glaucomas are predominately secondary to anterior uveitis and neoplasms; however, primary open-angle glaucoma occurs. In horses, the glaucomas appear under-diagnosed because applanation tonometry is not routinely done; the glaucomas appear most frequently in older animals, the Appaloosa breed, and with concurrent anterior uveitis. In cattle, the glaucomas have been associated with congenital iridocorneal anomalies and anterior uveitis. Diagnostic procedures essential to manage the glaucomas in animals include tonometry, ophthalmoscopy (direct and indirect), and gonioscopy (visualization of the iridocorneal angle). The clinical signs of the glaucomas are traditionally divided into acute and chronic; in reality, most cases of acute glaucoma are superimposed on chronic glaucoma rather than occurring as singular events. Most dogs with early to moderate chronic glaucoma are not taken to the veterinarian because the early clinical signs—sluggish to slightly dilated pupils, mild bulbar conjunctival venous congestion, and early enlargement of the eye (buphthalmia or megaloglobus)—are so subtle. To detect early glaucoma, tonometry should be routinely performed on high-risk breeds of dogs as part of the general physical examination. The choice of medical or surgical treatment, or most frequently a combination of both, is based on the progressive iridocorneal angle closure that occurs in most of the canine glaucomas. For open-angle glaucoma in dogs, short- and longterm management is by treatment with miotics, carbonic anhydrase inhibitors, osmotics, and β-blocking adrenergics. Surgical procedures for glaucoma in dogs have traditionally provided only short-term resolution because the filtering fistulae eventually scar over and fail. More recently, anterior chamber shunts, with and without valves, offer improved results. Antifibrotic drugs, such as mitomycin C and 5-fluorouracil, may delay or prevent scarring of the alternate aqueous outflow channels and prolong their function. Lens Cataracts are an opacity of the lens or its capsule and should be differentiated from the normal increase in nuclear density (nuclear sclerosis) that occurs in older animals. Cataracts usually are classified by their age of onset (congenital, juvenile, senile), anatomical location, cause, degree of opacification (incipient, immature, mature, hypermature), and shape. Cataracts (often inherited) occur more commonly in dogs than in other species (Table: Inherited Cataracts in Domestic Animals ). Other etiologies include diabetes mellitus, malnutrition, radiation, inflammation, and trauma. In cats and horses, most cataracts are secondary to anterior uveal inflammation. Sight may be regained in young dogs, cats, and horses when cataracts undergo sufficient spontaneous resorption; congenital nuclear cataracts in young animals may reduce in size with growth of the lens to permit restoration of vision as the animal matures. Animals with immature and incomplete cataracts may benefit from topical ophthalmic atropine 2-3 times/wk, which allows vision around a central cataract. In general, the only definitive therapy for cataracts is surgical removal of the lens. Lens displacement (subluxation, anterior or posterior luxation) occurs in all species but is common as a primary inherited defect in several terrier breeds. Lens displacements also can be produced by trauma, enlargement of the globe with glaucoma, and degenerative zonular changes with chronic cataracts. Chlamydial Conjunctivitis: Introduction Etiology and Epidemiology: The disease in cats is also known as feline pneumonitis, which is largely a misnomer because chlamydiae rarely cause pneumonia in cats. The infection usually involves the eye and mucosa of the upper respiratory tract (rhinitis, sinusitis, pharyngitis). Chlamydial keratoconjunctivitis in lambs and goats can have significant economic impact, particularly in confinement flocks, in which up to 90% can become affected. Concurrently, lambs often have chlamydial polyarthritis ( Chlamydial Polyarthritis-serositis). Also, chlamydial abortions ( Abortion in Goats) have been seen in a goat herd affected simultaneously with chlamydial keratoconjunctivitis. Clinical Findings: Signs in cats range from serous to mucopurulent conjunctivitis and rhinitis. Early signs are unilateral, reddened, slightly swollen conjunctivae. The incubation period after exposure to an infected cat is 3-10 days. Bilateral conjunctivitis develops after a few days, and the conjunctivae become hyperemic and chemotic, with prominent follicles on the inside of the third eyelid in more severe cases. In some cats, clinical signs can last for weeks despite treatment, and recurrence is not uncommon. Similar eye lesions occur in sheep and goats. Secondary infections in lambs and goats are also common and, if untreated, can lead to severe complications. Lesions:
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Inflammatory reactions in the conjunctivae are prominent, and various cells such as neutrophils, lymphocytes, plasma cells, and macrophages infiltrate early in the disease. These cells, together with conjunctival epithelial cells containing chlamydial inclusions, are found in smears made from conjunctival scrapings. Gastric epithelial cells of cats are also infected. Diagnosis: Diagnosis can be confirmed by demonstration of chlamydial inclusions in exfoliative cytologic preparations or by isolation of the chlamydial organism. Chlamydial conjunctivitis in cats should be differentiated from herpesvirus and calicivirus infections, and in lambs and goats from mycoplasmal and other bacterial infections (eg, “pinkeye”). Prevention and Treatment: Vaccines are available for chlamydiosis in cats but not for other species. The feline chlamydial vaccine does not completely protect the cat but significantly reduces severity and infection rates. All C psittaci isolates are susceptible to tetracyclines. In cats, ophthalmic ointments that contain tetracycline may be the only therapy necessary. However, in severe or recurring cases, oral or parenteral treatment with tetracyclines is advisable. Cats that are pregnant or have kidney disease should be treated with erythromycin. Daily feeding of 150-200 mg of chlortetracycline to affected lambs in feedlots also reduces the incidence of conjunctivitis and polyarthritis. To reduce recurrence, treatment in cats, lambs, and goats should be continued for 7-10 days after clinical signs disappear. Equine Uveitis: Introduction (Equine recurrent uveitis, Periodic ophthalmia, Recurrent iridocyclitis, Moon blindness) Recurrent episodes of inflammation of the uveal tract (iris, ciliary body, choroid) in one or both eyes of Equidae are responsible for the clinical signs and sequelae. This disease is the leading cause of blindness in horses. Etiology and Epidemiology: The inciting cause is often not identified. Proposed causes have included trauma and bacterial, viral, fungal, parasitic, and other systemic diseases, but the basic pathophysiology that allows perpetuation of the uveitis remains elusive. Leptospirosis and, specifically, exposure to Leptospira interrogans pomona is the most commonly implicated infectious cause of equine uveitis. Aberrant ocular migration of Onchocerca cervicalis microfilariae is the most commonly implicated parasitic cause of recurrent uveitis. Live microfilariae can be identified as an incidental finding in normal eyes, and uveal inflammation is believed to occur in response to dying microfilariae. Clinical Findings: Acute signs include varying degrees of blepharospasm, lacrimation, photophobia, conjunctival and ciliary injection, peripheral corneal edema and vascularization, aqueous flare, hypopyon or hyphema, miosis, a swollen dull iris, hypotonia, vitreal inflammation, and retinal vasculitis or peripapillary inflammation. Subacute, chronic, or recurrent cases have some of the same lesions and may also have sequelae (anterior and posterior synechiae, cataracts, lens luxation, pigment changes in the iris, vitreal debris, peripapillary retinal scars, or retinal detachments) in addition to acute lesions. Cataracts and pupillary seclusion are the most frequent causes of blindness in horses suffering from uveitis. Equine uveitis is the most common cause of cataracts in horses, and these horses are poor candidates for cataract surgery. Occasionally, glaucoma with buphthalmos develops secondary to lens luxation, anterior synechiae, or pupillary seclusion. Diagnosis: Ophthalmic signs suffice for diagnosis. Ulcerative diseases of the cornea should be ruled out by fluorescein staining. Lyme disease ( Borreliosis: Introduction , Avian Spirochetosis: Introduction) has been confirmed as a potential cause of uveitis in horses, and serology may be necessary for diagnosis. Horses with Lyme disease generally have systemic illness as well as uveitis. Treatment: Treatment must be aggressive to reduce ocular inflammation quickly, to prevent as many sequelae as possible, and to reduce the likelihood of chronic active inflammation or rapidly recurring episodes. Topical and systemic anti-inflammatory therapy are similar regardless of the suspected cause. High-quality, high-potency, topical corticosteroids are indicated, because lesser steroids do not effectively reduce inflammation in the uveal tract. Topical products should contain 0.1% dexamethasone or 1% prednisolone acetate and should be administered 4-12 times/day, depending on the severity of inflammation and on the preparation. Topical atropine is also essential; it dilates the pupil to prevent synechiae and provides analgesia through its cycloplegic action, which prevents painful ciliary spasm. Atropine (1%) should be used up to 4 times/day until the pupil dilates, and then gradually decreased. More frequent instillation of atropine requires close monitoring for reduced gut motility, fecal consistency, or other signs that might be consistent with atropine-induced colic. The topical NSAID facilitate mydriasis via their antiprostaglandin action.
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Systemic antibiotics usually are not indicated unless the uveitis appears to be septic, the horse is febrile, or leptospirosis or Lyme disease has been identified as the cause. Ivermectin (200 µg/kg, once) or a daily dose of diethylcarbamazine (2-3 mg/lb [4.4-6.6 mg/kg], PO, for 21 days) has been used for this, although ivermectin may not be completely effective; with either drug, the eyes should also be treated topically with corticosteroids during the course of larvicidal therapy to prevent inflammation associated with the dying microfilariae. Prognosis and Prevention: Prognosis varies directly with duration of signs before institution of adequate therapy; if several days have elapsed, permanent sequelae such as synechiae and blindness may develop. Immunization of horses has been recommended when L pomona has been implicated as the cause of endemic outbreaks. However, this practice is controversial, of questionable benefit, and requires administration of a bovine bacterin not approved for use in horses. It is also possible that administration of multivalent Leptospira bacterin to a seropositive horse with prior or active uveitis may potentiate the uveitis due to immunologic stimulation. Therefore, immunization should be limited to seronegative horses in selected instances in which a group of horses is believed to be at increased risk for leptospirosis-induced uveitis. Infectious Keratoconjunctivitis: Introduction (Pinkeye, Infectious ophthalmia) Infectious keratoconjunctivitis of cattle, sheep, and goats is characterized by blepharospasm, conjunctivitis, lacrimation, and varying degrees of corneal opacity and ulceration. In cattle, Moraxella bovis is the only commonly recognized cause of infectious keratoconjunctivitis. Most other ocular infections of cattle are characterized by conjunctivitis and minimal or absent keratitis. The primary differential diagnosis is infectious bovine rhinotracheitis (IBR), which causes severe conjunctivitis and edema of the cornea near the corneoscleral junction, but other corneal involvement is uncommon. Other organisms that may cause conjunctivitis of cattle, either alone or in conjunction with M bovis , include Mycoplasma spp and Neisseria spp . Infection with IBR or other microbes may increase the severity of infection with M bovis . In sheep, infection with Chlamydia psittaci is most common. Nonchlamydial infections may be caused by rickettsialike organisms ( Colesiota conjunctivae ), Mycoplasma spp , and aerobic bacteria, notably Neisseria ovis . In goats, mycoplasmal infections are most common, although aerobic bacteria also have been isolated. Clinical Findings: One or both eyes may be affected. In cattle, dry, dusty environmental conditions; shipping stress; bright sunlight; and irritants such as pollens, grasses, and flies tend to predispose to and exacerbate the disease. Flies also serve as vectors. The initial signs are photophobia, blepharospasm, and excessive lacrimation; later, the ocular discharge may become mucopurulent. Conjunctivitis, with or without varying degrees of keratitis, is always present. In sheep and goats, concurrent polyarthritis may be present. In goats, mammary gland and uterine infection may also occur simultaneously with keratoconjunctivitis. Lesions: Lesions vary in severity. In cattle, one or more small ulcers occur near the center of the cornea (but occasionally near the limbus), which are often preceded by cloudiness of the central cornea. Initially, the cornea is clear around the lesion, but within a few hours a faint haze appears that subsequently becomes more dense. About 1 wk after the lesion first appears, blood vessels begin to invade the cornea (adventitious vascularization) from the limbus toward the ulcer. Diagnosis: In all species, presumptive diagnosis is based on ocular signs and concurrent systemic disease. It is important to distinguish that the lesions are not due to foreign bodies or parasites (see eyeworms of large animals , above Eyeworms of Large Animals) In IBR, upper respiratory signs and conjunctivitis predominate, while keratitis accompanied by ulceration is rare. In bovine malignant catarrhal fever, respiratory signs are prominent with primary uveitis and associated keratitis. Prevention and Treatment: Separation of infected animals from normal animals is beneficial when possible. Ultraviolet radiation from sunlight may enhance disease (particularly in cattle); therefore, affected animals should be provided with shade. Moraxella bovis bacterins are available and can be administered before the beginning of fly season. cattle should not be vaccinated during an outbreak with M bovis . Oxytetracycline is generally considered the drug of choice for systemic therapy because it is concentrated in corneal tissue. It cannot, however, be injected in the subconjunctiva because it will cause conjunctival necrosis. topical application is often not cost-effective or practical. Effective antibiotics for topical ophthalmic use include triple antibiotic, gentamicin, and a combination oxytetracycline/polymyxin B ointment. For sheep and goats, in which chlamydial and mycoplasmal infections are most likely, respectively, topical tetracycline, oxytetracycline/polymyxin B, or erythromycin ointments are the treatments of choice.

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Neoplasia Of The Eye And Associated Structures: Introduction The different tissues of the eye and associated structures can develop primary neoplasms or can be the site of metastatic neoplasms. Ophthalmic neoplasms vary in frequency and importance in different species. Cattle The most frequent ophthalmic neoplasms in cattle are the squamous cell carcinoma complex and the orbital infiltration associated with lymphosarcoma ( Bovine Leukosis: Introduction). The latter, with extensive invasion of the orbital structures, results in progressive exophthalmia, reduced ocular mobility, exposure keratitis, and corneal ulcerations that can lead to perforation. It occurs most often in Herefords and rarely in other breeds. The etiology is multifactorial with heritability, sunlight, nutrition, and perhaps viral involvement. The cancerous or precancerous lesions are bilateral or multiple in the same eye in ~28% of cases. Ultraviolet radiation and a high plane of nutrition are contributing influences. The lesions usually begin as benign, smooth, white plaques on the conjunctival surfaces; they may progress to a papilloma and then a squamous cell carcinoma, or go directly to the malignant stage. Diagnosis usually is made by the typical clinical appearance but can be confirmed rapidly by cytologic examination of impression smears. The intraocular tumor invasion must be differentiated from severely disorganized eyes after trauma or infectious keratoconjunctivitis ( Infectious Keratoconjunctivitis: Introduction). Surgical excision is indicated for small lesions or for debulking the larger lesions before cryotherapy or hyperthermia. For advanced lesions confined to the globe, enucleation is recommended. Owners of problem herds should be advised of the heritability factor, and affected animals and their offspring culled to decrease the incidence of the tumor. Otitis Externa: Introduction Otitis externa is an acute or chronic inflammation of the epithelium of the external auditory meatus, sometimes involving the pinna. It is characterized by erythema, increased discharges or desquamation of the epithelium, and varying degrees of pain and pruritus. It is the most common disease of the ear canal in dogs and cats, and it usually has a multifactorial etiology. It is occasionally seen in rabbits, in which it is usually due to the mite Psoroptes cuniculi . It is uncommon in large animals. Clinical Findings and Diagnosis: Unless all the causes are identified and treated, recurrence may be expected. For animals with unilateral signs, the unaffected ear should be examined first. The presence of many neutrophils phagocytizing bacteria confirms the pathogenic nature of the organisms. The yeast Malassezia canis is found in low numbers in the ear canals of many normal dogs and cats. Because yeasts colonize the surface of the ear canal, they are most easily found adhered to clumps of exfoliated squamous cells. No more than two or three organisms should be present on any aggregate of cells from a normal animal. Ear swab smears should be examined for eggs, larvae, or adults of the ear mite Otodectes cynotis because a small population of mites may be missed on otoscopic examination. Similarly, smears from rabbits' and goats' ears should be examined for Psoroptes cuniculi . Rarely, refractory ceruminous otitis externa may be associated with localized proliferation of Demodex sp in the external ear canals of dogs and cats. Failure to use systemic antimicrobial therapy is an important perpetuating cause of chronic ear disease in dogs. When unidentified yeasts or hyphal organisms are seen in significant numbers in cytologic smears, the species should be identified through culture. Histopathologic changes associated with chronic otitis externa are often nonspecific. Histopathologic evidence of a hypersensitivity response may support a recommendation for intradermal allergy testing or for a hypoallergenic diet trial. Additionally, biopsies from animals with chronic, obstructive, unilateral otitis externa may reveal whether neoplastic changes are present. Radiography of the osseous bullae is indicated when proliferative tissues prevent adequate visualization of the tympanic membrane, when otitis media is suspected as a cause of relapsing bacterial otitis externa, and when neurologic signs accompany otitis externa. Treatment: Underlying primary, predisposing, and perpetuating causes should be identified and corrected. In animals with chronic or painful acute otitis externa, proper cleaning of the ear canals requires general anesthesia. The ears may be flushed with an antibacterial cleansing solution such as chlorhexidine or polyhydroxydine or with a ceruminolytic solution such as dioctyl sodium sulfosuccinate (DSS). If the tympanic membrane is ruptured, detergents and DSS are contraindicated; milder cleansers (eg, saline, carbamide peroxide) should be used to flush the ear.

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Therapy should be specific and simple. In treatment of acute bacterial otitis externa, antibacterial agents in combination with corticosteroids should be used. The corticosteroids reduce exudation, pain, and swelling, and decrease glandular secretions. The least potent corticosteroid that will reduce the inflammation should be used; many times, this can be accomplished with hydrocortisone. Bacterial superinfections develop in some animals treated with fungicidal agents or inappropriate antibacterials, and fungal overgrowth develops in some treated with antibacterial agents. When such infections arise, treatment should be with antibacterial and antifungal drugs. Animals with recurring bacterial otitis externa and a history of infection with Otodectes cynotis should be treated with a topical product that contains antibacterial and antiparasitic agents to ensure that undetected low-grade parasitic infections are eliminated. Substances that are usually not irritating in normal ear canals may cause irritation in an ear that is already inflamed. This is particularly true of propylene glycol. Powders form irritating concretions within the ear canal and should not be used. Otitis Media And Interna: Introduction Otitis media, inflammation of the middle ear structures, is usually due to extension of infection from the external ear canal or to penetration of the tympanic membrane by a foreign object. It occurs in all species but is most common in dogs, cats, and rabbits. Extension of infection through the auditory tube occurs in dogs, cats, and pigs. Hematogenous spread of infection to these areas is possible but rare. Otitis media can lead to otitis interna and inflammation of the inner ear structures and can result in loss of equilibrium and deafness. Clinical Findings and Diagnosis: The signs of otitis media and otitis externa ( Otitis Externa: Introduction) may be similar. Head shaking, rubbing the affected ear on the floor, and rotating the head toward the affected side are usually present. The ear is usually painful, with a discharge and inflammatory changes in the ear canal. Because the facial and sympathetic nerves course through the middle ear, facial nerve paralysis or Horner's syndrome (miosis, ptosis, enophthalmos, and protrusion of the nictitans), or both, may be present on the same side as the otitis media. The animal with otitis interna may circle and fall toward the affected side and will have generalized incoordination that may be severe enough to cause difficulty in rising and ambulating. Nystagmus may also be seen with otitis interna and is characterized as a spontaneous, horizontal to rotary type, with the fast phase away from the affected side. Otitis media should be suspected in cases of severe purulent otitis externa. Otitis interna should be strongly suspected if peripheral vestibular signs are present. Treatment and Prognosis: Otitis media with an intact tympanum usually responds well to systemic antibiotic therapy; however, if chronic otitis externa exists and the tympanum is ruptured, the chances of successful treatment are reduced. If facial and sympathetic nerve deficits develop, they may persist even after the infection has been cleared. Otitis interna usually responds well to long-term antibiotic therapy, but some neurologic deficits (eg, incoordination, head tilt, deafness) may persist for life. Animals recovering from otitis interna should be given adequate time to adapt to any persistent neurologic deficiencies. Tumors Of The Ear Canal: Introduction These tumors may arise from any of the structures lining or supporting the ear canal, including the squamous epithelium, the ceruminous or sebaceous glands, or the mesenchymal tissues. They are more likely to arise in the external ear canal and auditory meatus than in the middle and inner ear cavities. They are relatively uncommon compared with cutaneous tumors elsewhere on the body. Signs include chronic otic discharges and odors, swelling or abscesses around the ears, deafness, and signs of middle or inner ear involvement, including head tilt, ataxia, nystagmus, or Horner's syndrome. Because the signs associated with tumors of the ear canal often mimic those seen in chronic otitis externa, lesions may be advanced by the time a definitive diagnosis is made. Squamous cell carcinomas are most frequent on the pinnae and are the most common tumor of the middle and inner ear. The lesions are usually ulcerated. When present in the middle and inner ears of cats, signs include facial paralysis, ataxia, head tilt, nystagmus, and Horner's syndrome. Prognosis is poor. Treatment consists of early surgical intervention combined with radiation therapy to slow the progress of local disease. For ceruminous gland tumors, see Ceruminous Gland Tumors.

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Generalized disease Actinobacillosis: Introduction Actinobacillosis is caused by gram-negative coccobacilli that belong to the genus Actinobacillus . It almost always involves soft tissue, including lymph nodes through which the organisms frequently spread, but also may involve adjacent bony tissue. Other species of bacteria may be present at the site of infection. In general, therapy should involve surgical debridement and lavage (when possible), and oral potassium iodide (food safety issues have limited the usefulness of this product) or an antimicrobial agent to which the pathogen is susceptible and that reaches therapeutic concentrations in active form at the site of infection. It has been recommended that this organism be classified as Haemophilus actinomycetemcomitans based on the similarity of its DNA with other bacteria belonging to the genus Haemophilus . Actinobacillus lignieresii is the etiologic agent of wooden tongue, primarily seen in cattle but also in sheep, horses, pigs, and dogs. Wooden tongue is characterized as a hard, tumorous abscess of the tongue.

Pus from the abscesses may contain small colonies of organisms surrounded by club-like processes of calcium phosphate. The combination of bacteria and club-like processes have the appearance of grayish white “sulfur granules” that are <1 mm in diameter. The organism is part of the normal flora of the mucous membranes of the animal's upper GI tract. It causes disease by gaining access to adjacent soft tissue via penetrating wounds and causing localized infections or spreading, via the lymphatics, to other tissues and organs. Although the disease caused by this organism is distributed worldwide, it is sporadic in its occurrence and, as such, is difficult to prevent. Treatment involves surgical debridement (when possible), and potassium iodide administered orally (should not be used in food-producing animals) or systemically administered antibacterial agents such as the tetracyclines, erythromycin, or tilmicosin. Actinomycosis: Introduction Actinomycosis is a disease process caused by gram-positive rods belonging to the genus Actinomyces . Unlike Mycobacterium or Nocardia spp , Actinomyces are acid-fast negative. These organisms are normal flora of the oral and nasopharyngeal mucous membranes. As a rule, treatment of actinomycosis should include surgical debridement (when possible) and antibacterial therapy. Actinomyces spp are susceptible to the β-lactam antimicrobial agents such as penicillins and cephalosporins but are resistant to sulfas. For animals allergic to penicillin, tetracyclines and erythromycin are reasonable alternatives. Actinomyces bovis is the etiologic agent of lumpy jaw in cattle.

Lumpy jaw is characterized as a swelling with draining tracts resulting from a chronic, progressive, indurated, granulomatous, suppurative abscess that most frequently involves the mandible, the maxillae, or other bony tissues in the head.

Disease occurs when A bovis is introduced to underlying soft tissue, via penetrating wounds of the oral mucosa from wire or coarse hay or sticks, and spreads to adjacent bone. Involvement of adjacent bone frequently results in facial distortion, loose teeth (making chewing difficult), and dyspnea from swelling into the nasal cavity. Culture results and histopathologic analysis of involved tissue can further confirm the diagnosis. Iodine treatment (tincture of iodine applied topically) has been used successfully in the past but is no longer recommended due to food safety issues. Actinomyces (Corynebacterium) pyogenes is the etiologic agent associated with a number of disease entities, primarily in cattle but also in goats, sheep, and pigs. These include acute and chronic suppurative mastitis, suppurative pneumonia (usually as a sequelae of acute bovine respiratory disease caused by Pasteurella haemolytica or P multocida ), septicemia, vegetative endocarditis, endometritis, septic arthritis, wound infections including umbilical infections, seminal vesiculitis (bulls and boars), and summer mastitis. Amyloidosis: Introduction Amyloidosis is a condition characterized by the excessive, extracellular deposition of inert protein fibrils. This material, called amyloid, may be deposited in a localized fashion or may be widely distributed throughout the body where it can cause damage by displacement of normal cells. If critical organs such as the kidneys, liver, or heart are involved, the disease may be fatal. Amyloidosis can affect all domestic mammals, and minor, asymptomatic deposition of amyloid is common in aged animals.
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Amyloid consists of inert fibrils derived from a large variety of precursor proteins, and amyloid can be classified on the basis of these fibril proteins. The most common form of amyloid, AA amyloid, develops as a sequela of chronic inflammatory diseases, chronic bacterial infections, and malignant tumors. It is a common cause of death in horses aggressively immunized for antiserum production. The AA fibrils are derived from serum amyloid A protein, a major acutephase protein produced by hepatocytes. AA amyloid is commonly deposited in parenchymal organs and may not cause clinical signs. The spleen is commonly affected. If the kidneys are involved then the presence of amyloid in glomeruli may lead to proteinuria, eventually resulting in renal failure. In contrast, AL amyloid (monoclonal immunoglobulin) consists of partially degraded immunoglobulin light chains. Its deposition results from the overproduction of monoclonal light chains in animals with multiple myeloma. It tends to be deposited in mesenchymal tissues, especially nervous tissues and joints. There are many recognized forms of hereditary amyloidoses, one of which has been described in Abyssinian cats. There is no specific therapy that can prevent the development of amyloidosis or promote the resorption of fibrils. Obviously, animals with conditions such as chronic abscesses or multiple myeloma should be treated to reduce the availability of fibril precursor protein. Amyloidosis is readily recognized at necropsy and in histologic sections by its affinity for Congo red dye. Anthrax: Introduction (Splenic fever, Charbon, Milzbrand) Anthrax is an acute, febrile disease of virtually all warm-blooded animals, including man. Etiology and Epidemiology: Bacillus anthracis is a gram-positive, nonmotile, spore-forming bacterium (4-8 × 1-1.5 µm). Strain virulence is associated with the presence of two plasmids (pX01 and pX02) that carry the genes coding for toxin and capsule production, respectively. Bacillus produces an edema toxin (an adenylate cyclase) and a lethal toxin (probably a metalloprotease). Both toxins gain entry to target cells by competitive binding with a third protein, protective antigen, that has a membrane translocation function. The toxins and the capsule are the primary virulence factors of the anthrax bacillus. Outbreaks of anthrax commonly are associated with neutral or alkaline, calcareous soils that serve as “incubator areas” for the organisms. Clinical Findings: Death may occur in cattle, sheep, or goats without any previous evidence of illness. There may be bloody discharges from the natural body openings. Lesions: Rigor mortis is frequently absent or incomplete. Dark blood may ooze from the mouth, nostrils, and anus with marked bloating and rapid body decomposition. The liver, kidneys, and lymph nodes usually are congested and enlarged. In pigs with chronic anthrax, the lesions usually are restricted to the tonsils, cervical lymph nodes, and surrounding tissues. The area around involved lymphatic tissues generally is gelatinous and edematous. Diagnosis: Anthrax must be differentiated from other conditions that cause sudden death. In cattle and sheep, clostridial infections, bloat, and lightning stroke may be confused with anthrax. Also, acute leptospirosis, bacillary hemoglobinuria, anaplasmosis, and acute poisonings by bracken fern, sweet clover, and lead must be considered in cattle. Treatment and Control: When a soil-borne outbreak occurs, it is best to use antibiotics for the sick animals and to immunize all apparently well animals in the herd and on surrounding premises. Anthrax in livestock can be controlled largely by annual vaccination of all grazing animals in the endemic area and implementation of control measures during outbreaks. Animals should not be vaccinated within 2 mo of anticipated slaughter. Because this is a live vaccine, antibiotics should not be administered within 1 wk of vaccination. Clostridial Diseases: Introduction Clostridial diseases can be divided into two categories: 1) those in which the organisms actively invade and reproduce in the tissues of the host with the production of toxins that enhance the spread of infection and are responsible for death (sometimes referred to as the gas-gangrene group); and 2) those characterized by toxemia resulting from the absorption of toxins produced by organisms within the digestive system (the enterotoxemias), in devitalized tissue (tetanus), or in food or carrion outside the body (botulism). If treatment for diseases in the first category is attempted, large doses of antibiotic are indicated to establish effective levels in the center of necrotic tissue where clostridia are found.
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Bacillary Hemoglobinuria (Red water disease) This acute, infectious, toxemic disease is caused by Clostridium haemolyticum ( C novyi type D). It affects primarily cattle but has also been found in sheep and rarely in dogs. Etiology: Clostridium haemolyticum is a soil-borne organism that may be found naturally in the GI tract of cattle. It can survive for long periods in contaminated soil or in bones from carcasses of animals that had been infected. After ingestion, latent spores ultimately become lodged in the liver. The incubation period is extremely variable, and the onset depends on the presence of a locus of anaerobiosis in the liver. Such a nidus for germination is most often caused by fluke infection, much less often by high nitrate content of the diet, accidental liver puncture, liver biopsy, or any other cause of localized necrosis. When conditions for anaerobiosis are favorable, the spores germinate, and the resulting vegetative cells multiply and produce β toxin (phospholipase C), which causes intravascular hemolysis and its sequelae, including hemolytic anemia and hemoglobinuria. Clinical Findings: Cattle may be found dead without premonitory signs. Usually, there is a sudden onset of severe depression, fever, abdominal pain, dyspnea, dysentery, and hemoglobinuria. Edema of the brisket may occur. Hgb and RBC levels are quite low. The duration of clinical signs varies from ~12 hr in pregnant cows to ~3-4 days in other cattle. The mortality in untreated animals is ~95%. Lesions: Dehydration, anemia, and sometimes subcutaneous edema are present. There is bloody fluid in the abdominal and thoracic cavities. An anemic infarct in the liver is virtually pathognomonic; it is slightly elevated, lighter in color than the surrounding tissue, and outlined by a bluish red zone of congestion. Diagnosis: The general clinical picture usually permits a diagnosis. The most striking sign is the typical port-wine-colored urine, which foams freely when voided or on agitation. The normal size and consistency of the spleen serve to exclude anthrax and anaplasmosis. Control: Early treatment with penicillin or broad-spectrum antibiotics is essential. Clostridium haemolyticum bacterin prepared from whole cultures confers immunity for ~6 mo. Big Head infectious disease, caused by Clostridium novyi , C sordellii , or rarely C chauvoei , is characterized by a nongaseous, nonhemorrhagic, edematous swelling of the head, face, and neck of young rams. Treatment is with broad-spectrum antibiotics or penicillin. Infectious Necrotic Hepatitis (Clostridium novyi [oedematiens] infection, Black disease) This acute, infectious disease of sheep is sometimes seen in cattle and is rare in pigs and horses. Etiology and Pathogenesis: The etiologic agent, Clostridium novyi type B, is soil-borne and frequently present in the intestines of herbivores; it may be present on skin surfaces and is a potential source of wound infections. Fecal contamination of pasture by carrier animals is the most important source of infection. The organism multiplies in areas of liver necrosis caused by migration of liver flukes and produces a powerful necrotizing toxin. The lethal and necrotizing toxins (primarily α toxin) damage hepatic parenchyma, thereby permitting the bacteria to multiply and produce a lethal amount of toxin. Clinical Findings: Usually, death is sudden with no well-defined signs. Affected animals tend to lag behind the flock, assume sternal recumbency, and die within a few hours. Most cases occur in the summer and early fall when liver fluke infection is at its height. Lesions: The most characteristic lesions are the grayish yellow necrotic foci in the liver that often follow the migratory tracks of the young flukes. Other common findings are an enlarged pericardial sac filled with straw-colored fluid, and excess fluid in the peritoneal and thoracic cavities. Usually, there is extensive rupture of the capillaries in the subcutaneous tissue, which causes the adjacent skin to turn black (hence the common name, black disease). Control: The incidence may be lowered by reducing the numbers of snails, usually Lymnaea spp , that act as intermediate hosts for the liver flukes or by otherwise reducing the fluke infection of sheep. Active immunization with C novyi toxoid is more effective. Long-term immunity is produced by one vaccination. After this, only new introductions to the flock (lambs and sheep brought in from other areas) need to be vaccinated.
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Malignant Edema This acute, generally fatal toxemia of cattle, horses, sheep, goats, and pigs is usually caused by Clostridium septicum , often accompanied by other clostridial species. Etiology: Clostridium septicum is found in soil and intestinal contents of animals (including man) throughout the world. Infection ordinarily occurs through contamination of wounds containing devitalized tissue, soil, or some other tissue-debilitant. Wounds caused by accident, castration, docking, insanitary vaccination, and parturition may become infected. Clinical Findings and Diagnosis: General signs, such as anorexia, intoxication, and high fever, as well as local lesions, develop within a few hours to a few days after predisposing injury. The local lesions are soft swellings that pit on pressure and extend rapidly because of the formation of large quantities of exudate that infiltrates the subcutaneous and intramuscular connective tissue of the affected areas. The muscle in such areas is dark brown to black. Accumulations of gas are uncommon. Severe edema of the head of rams occurs after infection of wounds inflicted by fighting. Horses and pigs are susceptible to malignant edema but not to blackleg.

( Clostridium septicum also causes braxy in sheep, a highly fatal infection characterized by toxemia and inflammation of the abomasal wall. This disease seems to be confined mostly to European sheep fed on “frosted” pasture.) Control: Bacterins are used for immunization. In endemic areas, animals should be vaccinated before they are castrated, dehorned, or docked. Calves should be vaccinated at ~2 mo of age. Botulism (Lamziekte) This rapidly fatal motor paralysis is caused by ingestion of the toxin of Clostridium botulinum . Etiology: Botulism is an intoxication, not an infection, and results from ingestion of toxin in food. Like tetanus toxin, botulinum toxin is a zinc-binding metalloprotease that cleaves specific proteins in synaptic vesicles. Dogs, cats, and pigs are comparatively resistant to all types of botulinum toxin when administered orally. Most botulism in cattle occurs in South Africa, where a combination of extensive agriculture, phosphorus deficiency in soil, and C botulinum type D in animals creates conditions ideal for the disease. Botulism in sheep has been encountered in Australia, associated not with phosphorus deficiency as in cattle, but with protein and carbohydrate deficiency, which results in sheep eating carcasses of rabbits and other small animals found on the range. Toxicoinfectious botulism is the name given the disease in which C botulinum grows in tissues of a living animal and produces toxins there. The toxins are liberated from the lesions and cause typical botulism. This has been suggested as a means of producing the shaker foal syndrome. Clinical Findings and Lesions: The signs of botulism are caused by muscle paralysis and include progressive motor paralysis, disturbed vision, difficulty in chewing and swallowing, and generalized progressive weakness. Death is usually due to respiratory or cardiac paralysis. The toxin prevents release of acetylcholine at motor end-plates. Passage of impulses down the motor nerves and contractility of muscles are not greatly hindered; only the passage of impulses from nerves to motor end-plates is affected. No characteristic lesions develop, and pathologic changes may be ascribed to the general paralytic action of toxin, particularly in the muscles of the respiratory system, rather than to the specific effect of toxin on any particular organ. Major clinical findings included drooling, inability to urinate, dysphagia, and sternal recumbency that progressed to lateral recumbency just before death. Skin sensation is usually normal, and withdrawal reflexes of the limbs are weak. Initially, clinical signs resemble second-stage milk fever ( Parturient Paresis In Cows: Introduction), but the cows do not respond to calcium therapy. In the shaker foal syndrome, foals are usually <4 wk old. They may be found dead without premonitory signs; most often, they exhibit signs of progressive symmetrical motor paralysis. Stilted gait, muscular tremors, and the inability to stand for >4-5 min are salient features. Other clinical signs include dysphagia, constipation, mydriasis, and frequent urination. As the disease progresses, dyspnea with extension of the head and neck, tachycardia, and respiratory arrest occur. Death occurs most often 24-72 hr after the onset of clinical signs. The most consistent necropsy findings are pulmonary edema and congestion and excessive pericardial fluid, which contains free-floating strands of fibrin. Diagnosis: The diagnosis is made by eliminating other causes of motor paralysis. Filtrates of the stomach and intestinal contents should be tested for toxicity in mice, but a negative answer is unreliable. Clostridia-associated Enterocolitis in Horses
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Clostridium difficile and C perfringens have been implicated in this acute, sporadic disease of horses characterized by diarrhea and colic. Because of uncertainty about the etiology, the condition is also referred to as idiopathic colitis. See also Clostridia-associated Enterocolitis. Etiology: The factors that trigger disease are not known, but it is presumed that some alteration in the normal flora permits excessive multiplication of the bacteria, which produce toxins capable of causing intestinal damage and systemic effects. Predisposing factors that have been suggested include change in diet and antibiotic therapy. Other host factors that may determine whether disease develops include age, immunity, and presence or absence of intestinal receptors for the clostridial toxins. Lesions: The characteristic lesion is a necrotizing enterocolitis. There is severe loss of colonic and cecal mucosal epithelial cells, hemorrhagic colitis and typhlitis, and thrombosis in capillaries of the intestinal mucosa. Diagnosis: Clinical features of the disease are similar to those of acute salmonellosis ( Salmonellosis: Introduction , Salmonellosis , Intestinal Salmonellosis , Salmonellosis) and Potomac horse fever ( Potomac Horse Fever). A definitive diagnosis depends on demonstration of toxins of C perfringens or C difficile in feces or intestinal fluid, as well as on recovery of large numbers of the bacteria through anaerobic culture. Demonstration of large numbers of large, grampositive rods in a fecal smear may be used as a presumptive indication of clostridia-associated enterocolitis. Enterotoxemias: Overview (Clostridium perfringens infection) Five types (A, B, C, D, and E) have been identified, but type E is of questionable significance in disease. Enterotoxemia Caused by Clostridium perfringens Types B and C Infection with types B and C causes severe enteritis, dysentery, toxemia, and high mortality in young lambs, calves, pigs, and foals. Types B and C both produce the highly necrotizing and lethal β toxin that is responsible for the severe intestinal damage. This toxin is sensitive to proteolytic enzymes, and disease is associated with inhibition of proteolysis in the intestine. Sow colostrum, which contains a trypsin inhibitor, has been suggested as a factor in the susceptibility of young piglets. Lamb dysentery: C perfringens type B in lambs up to 3 wk of age. Calf enterotoxemia: types B and C in well-fed calves up to 1 mo. Pig enterotoxemia: type C in piglets during the first few days of life. Foal enterotoxemia: type B in foals in the first week of life. Struck: type C in adult sheep. Goat enterotoxemia: type C in adult goats. Clinical Findings: Lamb dysentery is an acute disease of lambs <3 wk old. Lesions: Hemorrhagic enteritis with ulceration of the mucosa is the major lesion in all species. Control: Treatment is usually ineffective because of the severity of the disease. Type D Enterotoxemia (Pulpy kidney disease, Overeating disease) Etiology: The causative agent is C perfringens type D. However, predisposing factors also are essential; the most common of these is the ingestion of excessive amounts of feed or milk in the very young and of grain in feedlot lambs. In young lambs, the disease usually is restricted to the single lambs, because a ewe with twins seldom gives enough milk to allow enterotoxemia to develop. In the feedlot, the disease usually occurs in lambs switched rapidly to high-grain diets. As the starch intake increases, it provides a suitable medium for growth of the causative bacteria, which produce ε toxin. A major effect of the toxin is to cause vascular damage, particularly of capillaries in the brain. Clinical Findings: Usually, sudden deaths in the best-conditioned lambs are the first indication of enterotoxemia. In some cases, excitement, incoordination, and convulsions occur before death. Opisthotonos, circling, and pushing the head against fixed objects are common signs of CNS involvement; frequently, hyperglycemia or glycosuria is seen. Type D enterotoxemia occasionally occurs in young horses that have overeaten. Lesions: Necropsy may reveal only a few hyperemic areas on the intestine and a fluid-filled pericardial sac. The rumen and abomasum contain an abundance of feed, and undigested feed often is found in the ileum. Edema and malacia can be detected microscopically in the basal ganglia and cerebellum of lambs. Rapid postmortem autolysis of the kidneys has led to the popular name, pulpy kidney disease; however pulpy kidneys are by no means always found in affected young lambs and are seldom found in affected goats or cattle. Diagnosis:
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A presumptive diagnosis of enterotoxemia is based on sudden, convulsive deaths in lambs on carbohydrate-rich feed. Chloroform, added at one drop for each 10 mL of intestinal fluid, will stabilize any toxin present. Control: If the disease occurs consistently in young lambs on a property, ewe immunization probably is the most satisfactory method of control. Enterotoxemia in feedlot lambs can be controlled by reducing the amount of concentrate in the diet. When alumprecipitated toxoids or bacterins are used, the injection should be given at such a site that the cold abscesses, which commonly develop at the site of injection, can be removed easily during normal dressing and not blemish the carcass. Tetanus Tetanus toxemia is caused by a specific neurotoxin produced by Clostridium tetani in necrotic tissue. Almost all mammals are susceptible to this disease, although dogs are relatively resistant, and cats seem much more resistant than any other domestic or laboratory mammal. Birds are quite resistant; the lethal dose for pigeons and chickens is 10,000-300,000 times greater (on a body weight basis) than that for horses. Horses are the most sensitive of all species Etiology and Pathogenesis: Clostridium tetani , an anaerobe with terminal, spherical spores, is found in soil and intestinal tracts. In most cases, it is introduced into the tissues through wounds, particularly deep puncture wounds, that provide a suitable anaerobic environment. Often in lambs, however, and sometimes in other species, it follows docking or castration. Suitable conditions for multiplication occur when a small amount of soil or a foreign object causes tissue necrosis. The bacteria remain localized in the necrotic tissue at the original site of infection and multiply. As bacterial cells undergo autolysis, the potent neurotoxin is released. The neurotoxin is a zinc-binding protease that cleaves synaptobrevin, a vesicleassociated membrane protein. Usually, toxin is absorbed by the motor nerves in the area and passes up the nerve tract to the spinal cord, where it causes ascending tetanus. The toxin causes spasmodic, tonic contractions of the voluntary muscles by interfering with the release of neurotransmitters from presynaptic nerve endings. If more toxin is released at the site of the infection than the surrounding nerves can take up, the excess is carried off by the lymph to the bloodstream and thus to the CNS, where it causes descending tetanus. Even minor stimulation of the affected animal may trigger the characteristic muscular spasms. The spasms may be so severe as to cause bone fractures. Spasms affecting the larynx, diaphragm, and intercostal muscles lead to respiratory failure. Involvement of the autonomic nervous system results in cardiac arrhythmias, tachycardia, and hypertension. Clinical Findings: The incubation period varies from one to several weeks but usually averages 10-14 days. Spasms of head muscles cause difficulty in prehension and mastication of food, hence the common name, lockjaw. In horses, the ears are erect, the tail stiff and extended, the anterior nares dilated, and the third eyelid prolapsed. Walking, turning, and backing are difficult. Spasms of the neck and back muscles cause extension of the head and neck, while stiffness of the leg muscles causes the animal to assume a “sawhorse” stance. Sweating is common. General spasms disturb circulation and respiration, which results in increased heart rate, rapid breathing, and congestion of mucous membranes. Sheep, goats, and pigs often fall to the ground and exhibit opisthotonos when startled. Consciousness is not affected. Usually, the temperature remains slightly above normal, but it may rise to 108-110°F (42-43°C) toward the end of a fatal attack. Control: Active immunization can be accomplished with tetanus toxoid. Mares should be vaccinated during the last 6 wk of pregnancy and the foals vaccinated at 5-8 wk of age. In high-risk areas, foals may be given tetanus antitoxin immediately after birth and every 2-3 wk until they are 3 mo old, at which time they can be given toxoid. When administered in the early stages of the disease, curariform agents, tranquilizers, or barbiturate sedatives, in conjunction with 300,000 IU of tetanus antitoxin b.i.d., have been effective in the treatment of horses. Good results have been obtained in horses by injecting 50,000 IU of tetanus antitoxin directly into the subarachnoid space through the cisterna magna. The horse should be placed in a quiet, darkened box stall with feeding and watering devices high enough to allow their use without lowering the head. Slings may be useful for horses having difficulty standing or rising. The same approach as described for horses is used in treatment of dogs and cats, except that caution must be exercised in the IV administration of antitoxin because the equine antitoxin may induce anaphylaxis. A combination of chlorpromazine and phenobarbital may be used to reduce hyperesthetic reactions and convulsions. Erysipelas: Introduction Erysipelothrix rhusiopathiae (insidiosa) is distributed worldwide and can live in water, soil, decaying organic matter, slime on the bodies of fish, and in carcasses, even after processing. It causes swine erysipelas in its various forms; nonsuppurative arthritis in lambs and less frequently in calves and kids; postdipping lameness in sheep; uncommonly, jointill in goats ( Joint-ill); and acute septicemia in turkeys, ducks, and occasionally geese and other birds (see Erysipelas:

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Introduction , Swine Erysipelas ). In man, the infection is usually localized and is termed erysipeloid. (It should not be confused with erysipelas in man, a superficial cellulitis caused by group A β-hemolytic streptococci.)

It is resistant to certain commonly used antiseptics, such as formaldehyde, phenol, hydrogen peroxide, and alcohol, but is readily destroyed by caustic soda and hypochlorites. It is very sensitive to penicillin or ceftiofur but less so to the tetracyclines. Swine Erysipelas Clinical Findings: Acute septicemia, the skin (subacute) form, chronic arthritis, and vegetative endocarditis may occur in sequence, or separately. Pigs with acute septicemia may die suddenly without previous signs. This occurs most frequently in finishing pigs (100-200 lb [45-90 kg]). Acutely infected pigs are febrile (104-108°F [40-42°C]), walk stiffly on their toes, and lie on their sternums separately rather than piling in groups. They squeal plaintively when handled and may shift weight from foot to foot when standing. Skin discoloration may vary from widespread erythema and purplish discoloration of the ears, snout, and abdomen, to diamond-shaped skin lesions almost anywhere on the body, but particularly the lateral and dorsal parts. The lesions may occur as pink or light-purple areas of varying size that become raised and firm to the touch within 2-3 days of illness.

They may disappear or progress to a more chronic type of lesion such as diamond-skin disease. If untreated, necrosis and separation of large areas of skin can occur, but more commonly, the tips of the ears and tail may become necrotic and slough. Clinical disease is usually sporadic, and affects individuals or small groups, but sometimes larger outbreaks occur. Mortality is 0-100%, and death may occur up to 6 days after the first signs of illness. Acutely affected pregnant sows may abort, probably due to the fever, and suckling sows may show agalactia. Untreated pigs may develop chronic arthritis or vegetative valvular endocarditis; such lesions may also occur in pigs with no previous signs of septicemia. Valvular endocarditis is most common in mature or young adult pigs and is frequently manifested by death, usually from embolism. Chronic arthritis, the most common form of chronic infection, produces mild to severe lameness; the affected joints may be difficult to detect but tend to become visibly enlarged and firm. Mortality in chronic cases is low, but growth rate is retarded. Lesions: In acute infection, in addition to skin lesions, lymph nodes are usually enlarged and congested, the spleen is swollen, and the lungs are edematous and congested. Petechiae may be found in the kidneys, heart, and occasionally elsewhere. In chronic cases, there may be erosion of the articular cartilage, and ankylosis may result. Diagnosis: Acute erysipelas is difficult to diagnose in pigs showing only fever, poor appetite, and listlessness; however, because erysipelas responds extremely well to penicillin, a marked improvement within 24 hr supports the diagnosis. Prevention and Treatment: Killed bacterins or, in some countries, live-culture immunizing strains of low virulence for pigs are used. Penicillin is the drug of choice in acutely affected pigs, and it has been used concurrently with antiserum. Treatment of chronic infection is ineffective, and such pigs should be culled. Nonsuppurative Polyarthritis in Lambs This is an acute or, more commonly, chronic arthritis of one or more of the joints, usually of the limbs in lambs. Calves and kids also are affected sometimes. Etiology: The infective agent, Erysipelothrix rhusiopathiae , usually enters the body through wounds in young lambs, sometimes through the navel but more commonly after docking and castration. After a transient septicemia, the organism localizes in joints, without leaving evidence of infection at the site of entry. Clinical Findings: In the acute form, the characteristic lesion is a nonsuppurative arthritis manifested by heat and pain but only slight swelling of the joint tissues.
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In the chronic form, signs usually are not seen until lambs are 2-6 mo of age. Typically, several joints are affected and cause the lambs to have a stiff gait. Diagnosis: In outbreaks after docking and castration, a presumptive diagnosis can be made from the history and clinical signs. In sporadic cases, isolation and identification of the organism from affected joints should be attempted. The disease must be distinguished from polyarthritis due to other bacteria (eg, streptococcal joint-ill), white muscle disease, and other causes of lameness. Prevention and Treatment: Penicillin given early in acute disease is the best therapy but is of no value in the chronic form. Foot-and-mouth Disease: Introduction Foot-and-mouth disease (FMD) is a highly infectious viral infection of cattle, pigs, sheep, goats, buffalo, and artiodactyl wildlife species. It is characterized by fever; vesicles in the mouth and on the muzzle, teats, and feet; and death in young animals.

All species of deer and antelope, elephant, and giraffe are susceptible to FMD, but camels are resistant to natural infection, and the smaller camelids such as alpacas and llamas, although susceptible, are probably of no epidemiological significance. Etiology: FMD is caused by an aphthovirus of the family Picornaviridae. The virus is quickly inactivated outside the pH range of 6.0-9.0 and by desiccation and temperatures > 56°C, although residual virus may survive a considerable time when associated with animal protein (for instance, a proportion of FMD virus in infected milk will survive pasteurization at 72°C for 15 sec). The FMD virus is resistant to lipid solvents such as ether and chloroform. Because of the sensitivity of the virus to acid and alkaline pH, sodium hydroxide, sodium carbonate, and citric or acetic acid are effective disinfectants. Transmission, Epidemiology, and Pathogenesis: Transmission of FMD is generally by contact between susceptible and infected animals. Infected animals have a large amount of aerosol virus in their exhaled air, which can infect other animals via the respiratory or oral routes. All excretions and secretions from the infected animal contain virus, and virus may be present in milk and semen for up to 4 days before clinical signs appear. Aerosol FMD virus can spread a considerable distance as a plume, depending on weather conditions, particularly when the relative humidity is >60% and when the topography of the surface over which it is dispersing does not cause turbulence. Ruminants that have recovered from infection and vaccinated ruminants that have contact with live FMD virus can remain infected and carry the virus in the pharyngeal region—for up to 2½ years in cattle, 9 mo in sheep, and probably lifelong in the African buffalo. Clinical Findings: The incubation period for FMD is 2-14 days, depending on the infecting dose, susceptibility of the host, and strain of virus. After the incubation period, a fever of up to 107°F (41.5°C) develops, the animal is anorexic and salivates and stamps its feet as vesicles develop on the tongue, dental pad, gums, lips, and on the coronary band and interdigital cleft of the feet. Vesicles may also appear on the teats and udder, particularly of lactating cows and sows, and on areas of skin subject to pressure and trauma, such as the legs of pigs. Young calves, lambs, kids, and piglets may die before showing any vesicles because of virus-induced damage to the developing cells of the myocardium. Vesicles in the mouth, even when severe, usually heal within 7 days, although recovery of the tongue papillae takes longer. Diagnosis: In cattle and pigs, the clinical signs of FMD are indistinguishable from those of vesicular stomatitis ( Vesicular Stomatitis: Introduction), and in pigs from those of swine vesicular disease ( Swine Vesicular Disease: Introduction) and vesicular exanthema ( Vesicular Exanthema Of Swine: Introduction). Treatment and Control: Many countries free of FMD have a policy of slaughter of all affected and in-contact susceptible animals and strict restrictions on movement of animals and vehicles around infected premises. After slaughter, the carcasses are either burned or buried on or close to the premises, and the buildings are thoroughly washed and disinfected with mild acid or alkali and by fumigation. Tracing is carried out to identify the source of the outbreak and premises to which FMD virus could have already been transmitted by infected animals or animal products, contaminated vehicles or people, or aerosol. In areas or countries free of FMD in which this is not possible, control is by movement restriction, quarantine of affected premises, and vaccination around (and possibly within) the affected premises. This has the disadvantage that many carrier animals may remain after the outbreak, and quarantine may not be sufficiently long to prevent their subsequent movement. FMD in the
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unvaccinated population is high and climatic conditions are suitable for aerosol transmission of the virus. FMD vaccine is a killed preparation and, at best, affords good protection against challenge for 4-6 mo. Cryptococcosis This systemic fungal disease may affect the respiratory tract, CNS, eyes, and skin (particularly of the face and neck of cats). The fungus is found in soil and fowl manure, especially in pigeon droppings. Transmission is by inhalation of spores or contamination of wounds. Cryptococcosis is most common in dogs and cats but also occurs in cattle, horses, sheep, goats, birds, and wild animals. Clinical Findings and Lesions: Bovine cryptococcosis has been associated only with cases of mastitis, and many cows in a herd may be infected. Affected cows have anorexia, decreased milk flow, swelling and firmness of affected quarters, and enlarged supramammary lymph nodes. The milk becomes viscid, mucoid, and gray-white, or it may be watery with flakes. In cats, upper respiratory signs are most common and include sneezing; mucopurulent, serous, or hemorrhagic unilateral or bilateral chronic nasal discharge; polyp-like mass(es) in the nostril; and a firm, subcutaneous swelling over the bridge of the nose. Cutaneous lesions are also common and are characterized by papules and nodules that are fluctuant to firm. Larger lesions tend to ulcerate, leaving a raw surface with a serous exudate. Neurologic signs associated with cryptococcosis of the CNS may include depression, changes in temperament, seizures, circling, paresis, and blindness. Ocular abnormalities may also occur, including dilated unresponsive pupils and blindness due to exudative retinal detachment, granulomatous chorioretinitis, panophthalmitis, and optic neuritis. In contrast to cats, dogs tend to have severe disseminated disease, and most have CNS or ocular involvement. Clinical signs are usually related to meningoencephalitis, optic neuritis, and granulomatous chorioretinitis. Few dogs have been reported with lesions in the nasal cavity. About 50% of dogs have lesions in the respiratory tract, usually the lungs, and most have granulomas throughout the body. The lesion is usually composed of aggregates of encapsulated organisms within a connective tissue reticulum. The cellular response is primarily macrophages and giant cells with a few plasma cells and lymphocytes. Epithelioid giant cells and areas of caseation necrosis are less common than with the other systemic mycoses. Diagnosis: The most rapid method of diagnosis is cytologic evaluation of nasal exudate, skin exudate, CSF, or samples obtained by paracentesis of the aqueous or vitreous chambers of the eye or by impression smears of nasal or cutaneous masses. Gram's stain is most useful; the organism retains the crystal violet while the capsule stains lightly red with safranin.

The capsule does not stain. The best stain for Cryptococcus is Mayer's mucicarmine because of its ability to stain the capsule. Immunofluorescent staining can also be used. The large capsule and thin cell wall of Cryptococcus differentiate it from Blastomyces. Treatment: Amphotericin has been used to successfully treat dogs and cats. Flucytosine can be used alone or in combination with amphotericin. However, when flucytosine is used alone, drug resistance may develop, so combination therapy with amphotericin is recommended. Treatment with orally administered ketoconazole, itraconazole, or fluconazole has become more popular than amphotericin B and flucytosine. Ketoconazole has been used to successfully treat cats with cryptococcosis. Ketoconazole has been used less commonly to treat infected dogs, and the response has not been as consistent as in cats. Leptospirosis: Introduction Infections may be asymptomatic or cause various signs, including fever, icterus, hemoglobinuria, renal failure, infertility, abortion, and death. After acute infection, leptospires frequently localize in the kidneys or reproductive organs and are shed in the urine, sometimes in large numbers for months or years. Because the organisms survive in surface waters for extended periods, the disease is often waterborne. Infection is commonly acquired by contact of skin or mucous membrane with urine and, to a lesser extent, by intake of urine-contaminated feed or water. If shedder animals are introduced into a herd previously free of the disease, leptospires are rapidly disseminated. Abortions and stillbirths may occur, most frequently during the middle or last third of gestation. The microscopic agglutination test (MAT) is the most commonly used serologic test for diagnosis of leptospirosis. It measures both IgM and IgG antibodies; IgM antibodies usually appear 6-12 days after infection, and IgG after 2-3 wk. MAT titers rise rapidly, then generally decline over several months to moderate levels that may persist for weeks to years. Demonstration of leptospires in urine or tissues is helpful in diagnosis. Leptospirosis in Cattle (Redwater of calves) Clinical Findings:
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Calves may have fever, anorexia, and dyspnea, and in Leptospira pomona infections, icterus, hemoglobinuria, and anemia. Body temperature may rise suddenly to 105-106°F (40.5-41°C). Hemoglobinuria rarely lasts longer than 48-72 hr. Icterus clears rapidly and is followed by anemia. The RBC begin to increase in number by 4-5 days and return to normal 710 days later. However, Leptospira hardjo infections usually do not cause hemolytic anemia, which makes diagnosis more difficult. Morbidity and mortality are higher in calves than in adult cattle. The milk is thick, yellow, and blood-tinged; it may contain clots, although there is little evidence of mammary inflammation. Milk production returns to normal in 10-14 days, even in the absence of treatment. Abortion and stillbirths, which are common in Leptospira pomona infections and sporadic in Leptospira hardjo infections, generally occur 3-10 wk after initial infection. The abortions are more common during the third trimester. An abortion storm in a breeding herd is often the first indication that leptospirosis exists, because the mild initial signs often pass unnoticed. Calves reared by previously infected cows are protected by colostral antibodies for up to 6 mo. The calves generally have an antibody titer similar to that of their dams. Lesions: In the acute form, anemia, icterus, hemoglobinuria, and submucosal hemorrhages are prominent. The kidneys are swollen, with multifocal petechial and ecchymotic hemorrhages that become pale with time. Petechiae in other organs are seen in fulminating cases; however, in the more prevalent Leptospira hardjo infections, the lesions are primarily restricted to the kidneys. Diagnosis: In herd evaluation, sera should be obtained from various age groups. Isolation of the causative agent constitutes the most definitive diagnostic method, but because leptospires are difficult to culture, it is not commonly performed. Elimination of brucellosis, campylobacteriosis, and trichomoniasis as the cause of an abortion outbreak is suggestive of leptospirosis. Treatment: Chlortetracycline and oxytetracycline have been reported to be successful if given early. When leptospirosis is diagnosed in pregnant beef cows during the early epizootic phase, further abortions can be prevented by prompt vaccination of the entire herd and simultaneous treatment of all animals with appropriate antibiotics. The antibiotic reduces the number of leptospires in the kidneys and other tissues, at least during treatment, and provides a measure of protection until immunity is induced by vaccination. In dairy herds, generally only the sick animals should be treated with antibiotics because the loss of market milk after treatment must be considered. Prevention: Annual vaccinations, confinement rearing, and chemoprophylaxis are used for control. Bacterins generally confer protection against abortions and death and significantly reduce renal infections, although some infections do occur. Leptospirosis in Sheep Prevalence of leptospirosis in sheep is lower than that in cattle, possibly due to less intensive husbandry methods and the tendency of sheep to avoid contact with surface water. Leptospirosis in Pigs Although pomona was the serovar most commonly found in pigs, recent serologic surveys indicate bratislava is the most widespread. Abortions occurring 2-4 wk before term are the most common manifestation of leptospirosis in pigs. Piglets produced at term may be dead or weak and may die soon after birth. Differential diagnoses include brucellosis, parvovirus, and SMEDI (stillbirth, mummification, embryonic death, and infertility). Leptospirosis in Dogs The most common serovars infecting dogs were reported to be canicola and icterohaemorrhagiae in older studies Clinical Findings: The incubation period is 4-12 days. Nonspecific signs such as fever, depression, anorexia, and generalized pain may be seen during this time. Vasculitis, thrombocytopenia, and a coagulopathy may develop. Within a few days, additional signs of uremia, such as dehydration, vomiting, and oral ulceration, are seen. Hematologic abnormalities include leukocytosis, lymphopenia, monocytosis, and thrombocytopenia. Serum chemistry may reveal azotemia and electrolyte disturbances secondary to the renal failure, including hyponatremia, hypochloremia, and hyperphosphatemia. Serum levels of hepatic enzymes (AST, ALT, alkaline phosphatase) and serum bilirubin increase if the liver is affected. Urine sediment usually contains RBC, WBC, and granular casts. Isosthenuria, proteinuria, and glucosuria reflect tubular damage. Lesions: In acute disease, the kidneys or liver, or both, are swollen. Hemorrhages may be present in any organ. Diagnosis:
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Diagnosis is based on demonstration of leptospires in urine or tissues (or both) and serology, in conjunction with typical clinical and laboratory abnormalities. Treatment: Renal failure and liver disease are treated with fluid therapy and other supportive measures to maintain normal fluid, electrolyte, and acid-base balance. Antibiotic therapy consists of penicillin, tetracycline, or doxcycline to eliminate leptospiremia, followed by tetracycline or doxycycline to eliminate the renal carrier phase. Tetracycyline should be used with caution in azotemic animals. The fluoroquinolone antibiotics such as enrofloxacin also appear to be leptospirocidal. Listeriosis: Introduction (Listerellosis, Circling disease) Listeriosis is a sporadic bacterial infection that affects a wide range of animals, including man and birds. Encephalitis or meningoencephalitis in adult ruminants is the most frequently recognized form. Etiology and Epidemiology: Listeria monocytogenes is a small, motile, gram-positive, nonspore-forming, extremely resistant, diphtheroid coccobacillus that grows under a wide temperature range, 39-111°F (4-44°C). Its ability to grow at 4°C is an important diagnostic aid (in the “cold enrichment” method) for isolation of the organism from brain tissue (but not from placental or fetal tissues). Primary isolation is enhanced under microaerophilic conditions. It is a ubiquitous saprophyte that lives in a plant-soil environment and has been isolated from ≥42 species of domestic and wild mammals and 22 species of birds, as well as fish, crustaceans, insects, sewage, water, silage and other feedstuffs, milk, cheese, meconium, feces, and soil. Grazing animals ingest the organism and further contaminate vegetation and soil. Animal-to-animal transmission occurs via the fecal-oral route. Listeriosis is primarily a winter-spring disease of feedlot or housed ruminants. The less acidic pH of spoiled silage enhances multiplication of L monocytogenes . Removal or change of silage in the ration often stops the spread of listeriosis; feeding the same silage months later may result in new cases. Pathogenesis: Listeria that are ingested or inhaled tend to cause septicemia, abortion, and latent infection. Those that gain entry to tissues have a predilection to localize in the intestinal wall, medulla oblongata, and placenta or to cause encephalitis via minute wounds in buccal mucosa or via inhalation or the conjunctiva. The various manifestations of infection occur in all susceptible species and are associated with characteristic clinical syndromes: abortion and perinatal mortality in all species, encephalitis or meningoencephalitis in adult ruminants, septicemia in neonatal ruminants and monogastric animals, and septicemia with myocardial or hepatic necrosis (or both) in poultry (see Listeriosis: Introduction , Listeriosis). Listeric encephalitis affects sheep, cattle, goats, and occasionally pigs. It is essentially a localized infection of the brain stem that occurs when L monocytogenes ascends the trigeminal nerve. Clinical signs vary according to the function of damaged neurons but often are unilateral and include facial paralysis and circling. Septicemic or visceral listeriosis is most common in monogastrics, including pigs, dogs, cats, domestic and wild rabbits, and many other small mammals. This form is also found in young ruminants before the rumen is functional. Though rare, septicemia has been reported in older domestic ruminants and deer. The septicemic form affects organs other than the brain, the principal lesion being focal hepatic necrosis. The uterus of all domestic animals, especially ruminants, is susceptible to infection with L monocytogenes at all stages of pregnancy, which can result in placentitis, metritis, fetal infection and death, abortion, stillbirths, neonatal deaths, and possibly viable carriers. The metritis has little or no effect on subsequent reproduction; however, listeria may be shed for ≥1 mo via the vagina and milk. Clinical Findings: Encephalitis is the most readily recognized form of listeriosis in ruminants. The course in sheep and goats is rapid, and death may occur 24-48 hr after onset of signs; however, the recovery rate can be up to 30%.

In cattle, the course is less acute, and the recovery rate approaches 50%. Lesions are localized in the brain stem, and the signs indicate dysfunction of the third to seventh cranial nerves. Initially, affected animals are anorectic, depressed, and disoriented. They may propel themselves into corners, lean against stationary objects, or circle toward the affected side. Facial paralysis with a drooping ear, deviated muzzle, flaccid lip, and lowered eyelid often develops on the affected side, as well as lack of a menace response and profuse, almost continuous, salivation; food material often becomes impacted in the cheek. Listeriosis is relatively uncommon in pigs.

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Listeric abortion usually occurs in the last trimester without premonitory signs. Fetuses usually die in utero, but stillbirths and neonatal deaths occur. The abortion rate varies and has been up to 20% in sheep flocks. Encephalitis and abortion usually do not occur simultaneously in the same herd or flock. Lesions: In listeric encephalitis, there are few gross lesions except for some congestion of meninges. In septicemic listeriosis, small necrotic foci may be found in any organ, especially the liver. In aborted fetuses, there is slight to marked autolysis, clear to blood-tinged fluid in the serous cavities, and numerous small necrotic foci (0.5-2 µm) in the liver, especially in the right half. Diagnosis: Samples of lumbosacral CSF can be collected under local anesthesia. In cases of listeriosis, the CSF has an increased protein concentration (0.6-2.0 g/L [normal 0.3 g/L]) and a mild pleocytosis composed of large mononuclear cells. Listeriosis can be confirmed only by isolation and identification of L monocytogenes . Specimens of choice are brain from animals with CNS involvement and aborted placenta and fetus. Listeriosis can be differentiated from pregnancy toxemia in ewes ( Pregnancy Toxemia In Ewes: Introduction) or ketosis in cattle ( Ketosis In Cattle: Introduction) by careful clinical examination, CSF changes, and 3-OH butyrate concentrations well below 3.0 mmol/L. Furthermore, pregnancy toxemia or ketosis, and facial and ear paralysis are absent. In cattle, the unilateral signs of trigeminal and facial paralysis (when present) help to differentiate listeriosis from bovine spongiform encephalopathy ( Bovine Spongiform Encephalopathy: Introduction), thromboembolic encephalitis ( Haemophilus Somnus Disease complex: Introduction), polioencephalomalacia ( Polioencephalomalacia: Introduction), sporadic bovine encephalomyelitis ( Sporadic Bovine Encephalomyelitis: Introduction), and lead poisoning ( Lead Poisoning: Introduction). Rabies ( Rabies: Introduction) must always be considered in the differential diagnosis of listeriosis. Treatment and Control: Listeria monocytogenes is susceptible to penicillin (the drug of choice), ceftiofur, erythromycin, and trimethoprim/sulfonamide. Zoonotic Risk: In cases with encephalitis, L monocytogenes is usually confined to the brain and presents little risk of transmission unless the brain is removed. Pregnant animals (including women) should be protected from infection because of danger to the fetus. Infected milk is a hazard because Listeria may survive certain forms of pasteurization. Neosporosis: Introduction Neosporosis has been recognized in dogs, cattle, sheep, goats, deer, horses, and experimentally rodents and cats. Etiology: Neospora caninum is an obligate intracellular protozoan parasite that has been confused previously with Toxoplasma gondii . Only asexual stages are known, and they resemble T gondii . The complete life cycle of N caninum is unknown, but it can be transmitted transplacentally in dogs, cattle, goats, sheep, and cats, and subsequent offspring may be affected. Tachyzoites are 5-7 × 1-5 µm, depending on the stage of division. They divide by endodyogeny. Tachyzoites are found in myocytes, neural cells, dermal cells, macrophages, and other cells. Tissue cysts up to 100 µm in diameter are found in neural cells; the cyst wall is amorphous and up to 4 µm thick. Cysts have no septa and enclose slender 7 × 1.5 µm bradyzoites. Clinical Findings and Lesions: In dogs, both pups and older dogs are affected. Not all littermates are affected. Most severe infections are in young pups, which typically develop an ascending paralysis of the limbs, particularly the hindlimbs. The paralysis is often progressive and results in rigid contracture of the muscles of affected limbs. In some dogs, only neural signs are seen. The syndrome of polyradiculoneuromyositis appears typical of neosporosis. Ulcerative dermatitis, hepatitis, pneumonia, and encephalitis may also occur. In dairy cattle, N caninum is a major cause of abortion in many countries, particularly in the USA. Calves may be aborted, stillborn, born underweight, weak, or paralyzed, or they may become paralyzed within 4 wk of birth. Nonsuppurative encephalitis is the main lesion in aborted fetal tissues. Abortion can occur throughout gestation, and some cows may abort again; dams of these calves are clinically normal. Diagnosis: An immunoperoxidase test using specific antibodies can identify N caninum in tissue sections or biopsy specimens. An indirect fluorescent antibody test can be used to detect antibodies. Treatment and Control: Drugs used to treat toxoplasmosis (sulfadiazine, daraprim, clindamycin) show some success in treating neosporosis. Until the definitive host and the sources of infections are identified, control is not possible. There is no vaccine.

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Peritonitis: Introduction Inflammation of the peritoneum may be acute or chronic, local or diffuse, and most commonly is secondary to contamination of the peritoneal cavity. Etiology: Primary peritonitis is infrequent. It may be caused by infectious agents such as feline infectious peritonitis virus ( Feline Infectious Peritonitis And Pleuritis: Introduction ), Nocardia spp , or Mycobacterium spp . to the peritoneal cavity is generally by the hematogenous route. Progression of primary peritonitis tends to be chronic (days to weeks). Secondary peritonitis is often acute and results in rapid, progressive, systemic illness. It is most commonly associated with GI perforation or dehiscence of visceral wound closure, or with perforation of other infected viscera (eg, prostatic or hepatic abscess, pyometra). Penetrating abdominal injuries may lacerate viscera or inoculate the peritoneal cavity with foreign material and microorganisms. Peritonitis may also occur secondary to chemical irritants (eg, bile, urine) and to other disease processes that allow transmural migration of bacteria (eg, neoplasia, visceral ischemia). Peritonitis from chemical irritation or foreign bodies (eg, sponge) may be septic or nonseptic. Septic peritonitis may remain localized if the omentum or mesentery contains the septic process, which sometimes results in formation of an abdominal abscess. Microorganisms associated with septic peritonitis reflect the source of contamination. A mixed bacterial population is seen in GI perforation (coliforms, anaerobes), whereas perforation of nongastrointestinal viscera (eg, gallbladder, uterus, prostate) are usually associated with one organism ( Escherichia coli ). In horses, Streptococcus equi and Rhodococcus(Corynebacterium) equi may be associated with peritonitis. Clinical Findings: Signs vary depending on the type of peritonitis (primary or secondary) and the presence of bacterial infection. Pyrexia is common but may be suppressed by prostaglandin inhibitors. Abdominal distention, which may be inapparent, usually is due to accumulation of peritoneal exudate and may be accompanied by hemorrhage, septicemia, toxemia, paralytic ileus, shock, and adhesions. Icterus may be present in generalized bile peritonitis. In small animals, anorexia and depression are often accompanied by vomiting, and feces may not be passed. Dehydration, hypovolemia, and sepsis may result in hypothermia and death due to loss of extravascular fluid volume. In horses, clinical signs include severe colic, ileus, distended intestines on rectal examination, gastric reflux, and occasionally diarrhea. The horse is restless and may lie down and roll intermittently. Tachycardia, weak pulse, poor peripheral perfusion, and pyrexia are common. Septic peritonitis is frequently fatal, despite intensive treatment. Treatment: Initial treatment must be directed toward stabilization of the metabolic consequences of peritonitis. Replacement fluids, electrolytes, plasma, or whole blood may be necessary to maintain cardiac output. Broad-spectrum antimicrobial therapy should be initiated, usually by a parenteral route. Aminoglycoside or quinoline antibiotics are efficacious against gramnegative organisms, and penicillins or cephalosporins are efficacious against gram positive organisms. Once the animal is stabilized, surgery is done to explore the abdomen and to repair any defects (eg, a ruptured viscus). Toxoplasmosis: Introduction Toxoplasma gondii is a protozoan parasite that infects most species of warm-blooded animals, including birds and man, throughout the world. Etiology and Pathogenesis: Members of the cat family are the only known definitive hosts for T gondii and, therefore, serve as the main reservoir. Three infective stages of T gondii have been identified: tachyzoites (the rapidly multiplying form), bradyzoites (tissue cyst form), and sporozoites (within oocysts). In unexposed cats after ingestion of uncooked meat containing tissue cysts, T gondii initiates enteroepithelial replication. Bradyzoites are released from tissue cysts by digestion in the stomach and small intestine, invade intestinal epithelium, and undergo sexual replication, culminating in the release of oocysts (10 µm diameter) in the feces. Oocysts are first seen in the feces at 3 days after infection and may be released for up to 20 days after infection. After exposure to air for 24 hr, oocysts sporulate, become infective, and may persist in the environment for up to 1 yr. Cats generally develop immunity to T gondii after the initial infection and, therefore, only shed oocysts once in their lifetime. In all warm-blooded animals, after ingestion of uncooked meat containing tissue cysts (carnivores) or feed contaminated with cat feces containing oocysts (herbivores), T gondii initiates extraintestinal replication. Bradyzoites and sporozoites, respectively, are released and infect intestinal epithelium. After several rounds of epithelial replication, tachyzoites emerge and disseminate via the bloodstream and lymph. Tachyzoites infect tissues throughout the body and replicate intracellularly until the cells burst, causing tissue necrosis. Tachyzoites measure 4-8 × 2-4 µm in diameter and stain with Giemsa. Young and immunocompromised animals may succumb to generalized toxoplasmosis at this stage. Older animals mount a powerful cell-mediated immune response to the tachyzoites (mediated by cytokines) and control the infection, driving the tachyzoites into the tissue cyst or bradyzoite stage. Tissue cysts are usually seen in neurons and in cardiac and skeletal muscle. Individual cysts are 50-150 µm in diameter and consist of an argyrophilic wall enclosing hundreds of sporozoites that stain well with periodic acid-Schiff stain. Tissue cysts remain viable in the host for many years.
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Clinical Findings: The tachyzoite is the stage responsible for tissue damage; therefore, clinical signs depend on the number of tachyzoites released, the ability of the host immune system to limit tachyzoite spread, and the organs damaged by the tachyzoites. Because adult immunocompetent animals control tachyzoite spread efficiently, toxoplasmosis is usually a subclinical illness. However, in young animals, particularly puppies, kittens, and piglets, tachyzoites spread systemically and cause interstitial pneumonia, myocarditis, hepatic necrosis, meningoencephalomyelitis, chorioretinitis, lymphadenopathy, and myositis. The corresponding clinical signs include fever, diarrhea, cough, dyspnea, icterus, seizures, and death. Toxoplasma gondii is also an important cause of abortion and stillbirth in sheep and sometimes in pigs and goats. After infection of a pregnant ewe, tachyzoites spread via the bloodstream to placental cotyledons, causing necrosis. Tachyzoites may also spread to the fetus, causing necrosis in multiple organs. Finally, immunocompromised adult animals (eg, cats infected with feline immunodeficiency virus) are extremely susceptible to developing acute generalized toxoplasmosis. Diagnosis: During T gondii infection, IgM antibodies appear early but generally do not persist past 3 mo after infection. Therefore, increased IgM titers (>1:256) are consistent with recent infection. In contrast, IgG antibodies appear by the fourth week after infection and may remain increased for years during subclinical infection. Thus, to be useful, IgG titers must be measured in paired sera from the acute and convalescent stages (3-4 wk apart) and must show a 4-fold increase in titer. Additionally, CSF and aqueous humor may be analyzed for the presence of tachyzoites or anti- T gondii antibodies. Microscopical examination of tissue sections may reveal the presence of tachyzoites, bradyzoites, or both. Toxoplasma gondii is morphologically similar to other protozoan parasites and must be differentiated from Sarcocystis sp (in cattle), Sarcocystis neurona (in horses), and Neospora caninum (in dogs). Treatment: For animals other than man, treatment is seldom warranted. Clindamycin is the treatment of choice for dogs and cats, at 10-40 mg/kg and 25-50 mg/kg respectively, for 14-21 days. Prevention and Zoonotic Risk: Toxoplasma gondii is an important zoonotic agent. Toxoplasmosis is a major concern for people with immune system dysfunction (eg, people infected with human immunodeficiency virus). In these individuals, toxoplasmosis usually presents as meningoencephalitis and results from the emergence of T gondii from tissue cysts located in the brain as immunity wanes rather than from primary T gondii infection. Toxoplasmosis is also a major concern for pregnant women because tachyzoites can migrate transplacentally and cause birth defects in human fetuses. All infective forms of T gondii are heat labile and are destroyed by dry heat at 150°F (65°C), boiling water, iodine, and ammonia. Therefore, toxoplasmosis can easily be prevented by several simple measures: All meat should be cooked thoroughly. Uncooked meat should not be fed to pet cats. Because it takes up to 24 hr for oocysts to become infective after exposure to air, litter boxes should be cleaned daily. Individuals should wash thoroughly after handling cat feces. Pregnant women should avoid handling cats and cleaning litter boxes. Tuberculosis: Introduction Tuberculosis (TB) is an infectious, granulomatous disease caused by acid-fast bacilli of the genus Mycobacterium . Etiology: Three main types of tubercle bacilli are recognized: human, bovine, and avian, respectively, M tuberculosis , M bovis , and M avium complex ( M avium-intracellulare-scrofulaceum ). The three types differ in cultural characteristics and pathogenicity. The two mammalian types are more closely related to each other than to the avian type. All three types may produce infection in host species other than their own. Mycobacterium tuberculosis is most specific; it rarely produces progressive disease in the lower animals other than nonhuman primates and occasionally in dogs, pigs, and birds. Mycobacterium bovis can cause progressive disease in most warm-blooded vertebrates, including man. Mycobacterium avium complex is the only species of consequence in birds, but it is also pathogenic for pigs, cattle, sheep, deer, mink, dogs, cats, and some cold-blooded animals. Pathogenesis: Inhalation of infected droplets expelled from infected lungs is the usual route of infection, although ingestion, particularly via contaminated milk, also occurs. Intrauterine and coital methods of infection are recognized less commonly. Inhaled bacilli are phagocytosed by alveolar macrophages that may either clear the infection or allow the mycobacteria to proliferate. In the latter instance, a primary focus may form, provoked by cytokines associated with a hypersensitivity reaction that consists of dead and degenerate macrophages surrounded by epithelioid cells, granulocytes, lymphocytes, and later, giant cells. The purulent to caseous, necrotic center may calcify, and the lesion may become surrounded by granulation tissue and a fibrous capsule to form the classic “tubercle.” The primary focus plus similar lesions formed in the regional lymph node is known as the “primary complex.” In alimentary forms of disease, the primary focus may be found in the pharynx or mesenteric lymph node or, less commonly, in the tonsil or intestine. The primary complex seldom heals in animals and may progress slowly or rapidly. Dissemination through vascular and lymphatic channels may be generalized and rapidly fatal, as in acute miliary TB. Nodular lesions may form in many organs,
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including the pleura, peritoneum, liver, kidney, skeleton, mammary glands, reproductive tract, and CNS. A prolonged, chronic course may also ensue, with lesions usually having a more localized pattern of distribution. Clinical Findings: Superficial lymph node enlargement may be a useful diagnostic sign when present. In pigs, lesions caused by M avium are most often seen in lymph nodes associated with the GI tract, although generalized disease does not occur. Diagnosis: The single most important diagnostic test for TB is the intradermal tuberculin test. Diagnosis on clinical signs alone is very difficult, even in advanced cases. Radiography is useful in nonhuman primates and small animals. Necropsy findings of the classical “tuberculous” granulomas are often very suggestive of the disease.

The delayed-type hypersensitivity response of the host, responsible for much of the pathology of TB, is fundamental to the tuberculin skin test that is widely used for diagnosis in large animals. The single intradermal (SID) test involves inoculation of mycobacterial antigen prepared from a filtrate of cultures of either M bovis or M tuberculosis . Purified protein derivative (PPD) preparations of the mycobacteria improve specificity.

In a reactor, the antigen stimulates a local infiltrate of inflammatory cells and causes skin swelling that can be detected by palpation and measured by calipers. The reaction is read between 48 and 72 hr for maximum sensitivity and at 96 hr for maximum specificity. Test sites used vary in sensitivity and between countries and include the neck region, anal or caudal fold at the tail base, and vulval lip. Control: The main reservoirs of infection are man and cattle; The three principal approaches to the control of TB are test and slaughter, test and segregation, and chemotherapy. The test and slaughter policy is the only one assured of eradicating TB and relies on the slaughter of reactors to the tuberculin test. In an affected herd, testing every 3 mo is recommended to rid the herd of individuals that can disseminate infection. Test and slaughter used only in the final stages of eradication. Treatment of cases of TB has been attempted using drugs that have had some success in man, eg, isoniazid, streptomycin, and para-aminosalicylic acid. Efficacy is limited, and there are overriding arguments against therapy, based on the removal of infected animals, zoonotic risks, and the danger of encouraging drug resistance. Treatment is therefore not advisable and is illegal in some countries. The BCG (bacille Calmette-Guérin) vaccine, sometimes used to control TB in man, has proved to be poor at protecting most animal species, and inoculation often provokes a severe local granulomatous reaction. Vesicular Stomatitis: Introduction Vesicular stomatitis is characterized by fever and vesicles on the mucous membranes of the mouth, epithelium of the tongue, teats, soles of the feet, coronary band, and occasionally other parts of the body. Cattle, horses, and pigs are naturally susceptible; sheep and goats are infected occasionally. Etiology and Epidemiology: The rod-shaped viruses belong to the rhabdovirus group There is no cross-immunity between the two serotypes or between the viruses of vesicular stomatitis, foot-and-mouth disease, vesicular exanthema, and swine vesicular disease. It is not as contagious as foot-and-mouth disease. The virus can spread rapidly in a herd, and up to 90% of the animals show clinical signs, and nearly all develop antibodies. Vesicular stomatitis usually occurs epidemically in temperate regions and endemically in warmer regions. Clinical Findings: The incubation period is 2-8 days, or possibly longer. Frequently, excessive salivation is the first sign. Examination of the mouth may reveal blanched, raised vesicles. The lesions vary in size; some are no larger than a pea, while others may involve the entire surface of the tongue. In horses, the lesions are principally confined to the upper surface of the tongue but may involve the inner surface of the lips, angles of the mouth, and the gums. In natural infections of pigs, foot lesions are frequent, and lameness often is the first sign observed. Body temperature may rise immediately before, or simultaneously

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with, the appearance of vesicles. Ordinarily, there are no complications and the disease is self-limiting, with recovery in ~2 wk. Diagnosis: When vesicular stomatitis affects horses under natural conditions, there is no serious diagnostic problem because horses are not susceptible to foot-and-mouth disease. Diagnosis is made on the distribution and character of the lesions, and the disease may be differentiated from horsepox by the absence of papules and pustules. Treatment and Control: Suspected cases should be brought immediately to the attention of state or federal authorities. There is no specific treatment. Vaccines are available in some Latin American countries. Equine Infectious Anemia: Introduction (Swamp fever) Equine infectious anemia (EIA) is an acute or chronic viral disease of Equidae, found wherever there are horses. Epidemiology and Transmission: In acute cases, the virus is in blood and all tissues and discharges. It persists in WBC of all infected horses for life and is quite stable in serum but is readily inactivated by common disinfectants that contain detergent. Ordinarily, the disease is detected only sporadically, but it may spread in epidemic form from obviously ill horses when bloodsucking flies are abundant or if contaminated needles or surgical instruments are used. Mares may infect their foals in utero. Clinical Findings: EIA is characterized by intermittent fever, depression, progressive weakness, weight loss, edema, and progressive or transitory anemia;

it tends to become an inapparent infection but occasionally results in death. In horses with active disease, the PCV and platelet count are decreased and monocytes are increased. In chronic infections, blood may contain WBC with stainable iron and have increased gamma globulin. Lesions: In acute cases, the spleen and splenic lymph nodes are enlarged. Microscopically, there is proliferation of reticuloendothelial cells in many organs, and periportal and perisinusoidal collections of round cells in the liver with accumulations of hemosiderin in Kupffer's cells. Diagnosis: Clinical diagnosis should be confirmed by the immunodiffusion or Coggins test, a simple and highly accurate serologic test to detect infection. EIA should be suspected if a horse has a history of weight loss accompanied by periodic fever, or if several horses in a group develop similar signs after introduction of new animals into a herd or death of a horse on pasture. Treatment and Control: No specific treatment or vaccine is available. General supportive therapy may help in an individual case, but an infected horse, especially one exhibiting clinical signs, should be considered a likely source of infection for other horses. Whenever a diagnosis is established, the infected horse should be promptly isolated from other horses and maintained in isolation if it is not to be euthanized. Because the horse fly is an important vector, stabling during the fly season helps to prevent spread of infection. Septicemia In Foals: Introduction Septicemia is a systemic disease involving the presence of bacteria or their toxins, or both, in the blood. Bacterial infection accounts for nearly one third of all foal mortality. Septicemia is the second most common problem of the equine neonate, second only to failure of passive transfer of maternal antibodies. The predominant bacteria involved in neonatal sepsis are the gram-negative organisms Escherichia coli , Klebsiella spp , Enterobacter spp , Actinobacillus spp , and Pseudomonas spp . Streptococcus spp is the most frequently isolated gram-positive organism, but it usually occurs in a mixed infection. The major risk factor that foals have after parturition is failure to receive adequate colostral antibodies. Foals in septic shock are severely depressed, recumbent, dehydrated, and tachycardic. Their mucous membranes are muddy, and hypotension, which manifests clinically as cold extremities, thready pulses, and poor capillary refill times, is evident. Foals may be hyper- or hypothermic. If the foal is to survive, sepsis must be recognized before it reaches this stage. The mare's udder is often distended with milk, indicating that the foal is not nursing at a normal frequency. The bacteria spread hematogenously to different organs, such as the lungs, intestines, CNS, and bone and joints. Septic foals are often neutropenic with a high ratio of band to segmented neutrophils. The neutrophils may exhibit toxic changes, which is highly suggestive of sepsis. Foals <24 hr old are often hypoglycemic. Fibrinogen levels >600 mg/dL in a

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foal <24 hr old is indicative of an in utero infection. Hypoxemia and a mixed respiratory and metabolic acidosis may be present on an arterial blood gas analysis. Because of the high correlation between failure of passive transfer of antibodies and septicemia, serum IgG levels should be measured in any questionably sick equine neonate. IgG levels of <200 mg/dL indicate complete failure of passive transfer of maternal antibodies. IgG levels of >800 mg/dL are optimal. Differential diagnoses include neonatal maladjustment syndrome ( Neonatal Maladjustment Syndrome: Introduction), hypoglycemia, hypothermia, neonatal isoerythrolysis (Extracorpuscular Abnormalities), white muscle disease ( Nutritional Myopathy of Calves and Lambs), prematurity, and uroperitoneum. In all cases of neonatal sepsis, immunologic support, in the form of IV plasma transfusions to raise the IgG levels to >800 mg/dL is important. Antibiotics are important to eliminate the infection. Foals suspected of being septic should be placed on broad-spectrum antibiotics active against both gram-positive and gram-negative organisms; 95% of cultured organisms are sensitive to a combination of amikacin sulfate and sodium ampicillin. Effective IV fluid therapy is needed to combat endotoxic shock. Lactated Ringer's plus 5% dextrose (120 mL/kg/day) is a good maintenance solution. Bicarbonate should not be used in cases of respiratory acidosis because it can increase CO2 levels. If the foal survives the initial problems, it has the potential of becoming a healthy and useful adult. African Swine Fever: Introduction African swine fever (ASF) is a highly contagious hemorrhagic disease of pigs that produces a wide range of clinical signs and lesions that closely resemble those of hog cholera ( Hog Cholera: Introduction). Etiology and Epidemiology: ASF virus is a large, enveloped DNA virus that replicates primarily in cells of the monoculear phagocytic system. It is currently classified as the only member of a family called African swine fever-like viruses. The virus is highly resistant to a wide pH range and to a freeze/thaw cycle and can remain infectious for many months at room temperature or when stored at 4°C. Although ASF virus can be adapted to grow in cells from different species, it does not replicate readily in any species other than swine. The disease is limited to all breeds and types of domestic pigs and European wild boar. Transmission and Pathogenesis: ASF virus is maintained in Africa by a natural cycle of transmission between wart hogs and the soft tick vector Ornithodoros moubata , which inhabits wart hog burrows and from which it is unlikely ever to be eliminated. The spread of virus from the wildlife reservoirs to domestic pigs can be either by the bite of an infected soft tick or by ingestion of wart hog tissues. Virulent viruses produce acute disease, and all body fluids and tissues contain large amounts of infectious virus from the onset of clinical disease until death. Pigs infected with less virulent isolates can transmit virus to susceptible pigs up to 1 mo after infection; blood is infectious up to 6 wk, and transmission can occur if blood is shed. The primary route of infection is the upper respiratory tract, and virus replicates in the tonsil and lymph nodes draining the head and neck; generalized infection rapidly follows via the bloodstream. High concentrations of virus are then present in all tissues. The factors that produce the hemorrhagic lesions are not defined, but the severe disruptions to the blood clotting mechanism play a major role. Virus is excreted mainly from the upper respiratory tract and is also present in secretions and excretions containing blood. Pigs that survive infection with the less virulent isolates are probably persistently infected for life and have circulating antibody, although they do not excrete virus or transmit virus to their offspring in utero. Their role in the epidemiology of the disease is not known, but they are resistant to disease when challenged with related virus genotypes. This challenge virus may replicate and be transmitted, either directly or indirectly, to other pigs. Clinical Findings and Lesions: Peracute, acute, subacute, and chronic forms occur, and mortality rates vary from 0 to 100%, depending on the virulence of the virus with which pigs are infected. Acute disease is characterized by a short incubation period of 5-7 days, followed by high fever (up to 42°C) and death in 7-10 days. The least variable clinical signs are loss of appetite, depression, and recumbency; other signs include hyperemia of the skin of the ears, abdomen, and legs; respiratory distress; vomiting; bleeding from the nose or rectum; and sometimes diarrhea. Abortion is sometimes the first event seen in an outbreak. The severity and distribution of the lesions also vary according to virulence of the virus. Hemorrhages occur predominantly in lymph nodes, kidneys (most frequently as petechiae), and heart; hemorrhages in other organs are variable in incidence and distribution. Diagnosis: ASF cannot be differentiated from hog cholera by either clinical or postmortem examination. Virus can be isolated by inoculation of primary cultures of pig monocytes, in which it produces hemadsorption of pig red cells to the surface of infected cells. Hog cholera virus does not replicate in these cells. Viral antigen can be detected in infected tissue smears or sections by staining with labelled antibodies (immunofluorescence), and viral DNA by the polymerase chain reaction or by hybridization of nucleic acid probes to tissue sections. The most appropriate tests for detecting antibody in serum or tissue

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fluids are the ELISA test, indirect immunofluorescence, and counterimmunoelectrophoresis; a number of other useful tests are available. Control: There is no treatment, and all attempts to develop a vaccine have been unsuccessful. Pigs that recover from infection with less virulent viral isolates are resistant to challenge with viruses of a different genotype in the absence of neutralizing antibody. Prevention therefore depends on ensuring that neither infected live pigs nor pig meat products are introduced into areas free of ASF. All successful eradication programs have involved the rapid diagnosis, slaughter, and disposal of all animals on infected premises. Edema Disease: Introduction ( Escherichia coli enterotoxemia) Edema disease is a peracute toxemia caused by specific serotypes of Escherichia coli that affects primarily healthy, rapidly growing nursery piglets. Etiology and Pathogenesis: Specific virulence factors are required, including the presence of adhesive fimbriae that promote small intestinal colonization, and a toxin initially entitled EDP or “edema disease principle.” The source of the infection is thought to be either the environment or the sow, and it is assumed that piglets become infected during nursing. A genetic susceptibility to edema disease has been previously suggested. Colonization of the small intestine, perhaps due to a genetic mechanism similar to that of F4 (K88) fimbriae, has been suggested as a potential factor in disease pathogenesis. Clinical Findings and Lesions: Clinical signs range from peracute death to CNS involvement with ataxia and recumbency. Edema disease usually occurs 1-2 wk after weaning and typically involves the healthiest animals in a group. Periocular edema, swelling of the facial region, open-mouth breathing, and anorexia are common. Edema disease is primarily a disease of the vasculature, and gross lesions consist of subcutaneous edema and edema in the submucosa of the stomach, particularly in the glandular cardia region. The edema fluid is usually gelatinous and may extend into the mesocolon. Fibrin strands may be found in the peritoneal cavity, and serous fluid may be found in both the pleural and peritoneal cavity. Microscopically, a degenerative angiopathy affecting arteries and arterioles is seen. Necrosis of the smooth muscle cells in the tunica media is present; however, thrombosis is not a feature. Lesions of focal encephalomalacia in the brain stem are characteristic and thought to be the result of vascular damage, leading to edema and ischemia. Diagnosis: The clinical history of peracute death in healthy, well-conditioned piglets, along with visual observation of periocular edema and extensive edema of the stomach and mesocolon, are helpful in diagnosis. Histopathologic evidence of focal encephalomalacia in the brain stem assists in differentiation of edema disease from other acute toxemias such as water deprivation toxicosis. Treatment and Control: Treatment and control can be frustrating. Porcine Reproductive And Respiratory Syndrome: Introduction Due to the initial inability to determine the cause, the syndrome was called “mystery swine disease.” Etiology and Epidemiology: The etiologic agent is a virus in the group Arteriviridae. The primary vector for transmission of the virus is the infected pig. Contact transmission has been demonstrated experimentally, and the spread of virus from infected seedstock originating from a single source has been described. Controlled studies have indicated that infected swine may be long-term carriers, capable of shedding virus for 3-4 mo. Aerosol transmission of the virus has been considered to be a potential route of transmission, particularly under conditions of high humidity, low temperatures, and low wind speeds. The role of fomites in transmission of the virus is not clear; however, the virus can be excreted in the urine and feces of infected pigs. Clinical Findings: PRRS appears to have two distinct clinical phases: reproductive failure and postweaning respiratory diseases. The reproductive phase of the disease includes increases in the number of stillborn piglets, mummified fetuses, premature farrowings, and weak-born pigs. Stillbirths and mummies may increase up to 25-35%, and abortions can exceed 10%. Anorexia and agalactia are evident in lactating sows and result in increased (30-50%) preweaning mortality. Suckling piglets develop a characteristic thumping respiratory pattern, and histopathologic examination of lung tissue reveals a severe, necrotizing, interstitial pneumonia. PRRS is capable of crossing the placenta in the third and possibly second trimester of gestation. Infection with PRRS virus results in destruction of mature alveolar macrophages, which has led to the hypothesis that infection results in the suppression of the immune system; however, controlled studies indicated that the virus may actually enhance specific parameters of the immune response.
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Diagnosis: The most commonly used tests are the ELISA or the indirect fluorescent antibody test. These tests measure IgG antibodies to PRRS virus. Treatment and Control: Currently, there are no effective treatment programs for acute PRRS. Attempts to reduce fever using nonsteroidal antiinflammatory drugs, or appetite stimulants (B vitamins) appear to have minimal benefit. Finally, a recently available commercial vaccine, licensed for use in piglets 3-18 wk old and in nonpregnant sows 3-4 wk before breeding, has been effective in controlling outbreaks and preventing economic losses. The vaccine is not approved for use in pregnant sows, boars, or herds that are negative for PRRS virus. Swine Vesicular Disease: Introduction Swine vesicular disease (SVD) is typically a transient disease of pigs in which vesicular lesions appear in the mouth and on the feet. It does not cause severe production losses but is of major economic importance because it must be differentiated from foot-and-mouth disease, eradication is costly, and embargoes on export of pigs and pork products are often imposed on nations not free of SVD. Pigs are said to be the only natural host. Etiology: The causal agent is an enterovirus of the Picornaviridae family. Clinical Findings and Lesions: The primary signs are vesicular lesions in the mouth, on the lips or snout, and on the feet, especially the coronary band. The lesions may be mild or inapparent, especially when pigs are kept on soft bedding. The lesions are similar to those of foot-and-mouth disease ( Foot-and-mouth Disease: Introduction), vesicular exanthema of swine ( Vesicular Exanthema Of Swine: Introduction), and vesicular stomatitis ( Vesicular Stomatitis: Introduction); however, the pig does not lose condition, and the lesions heal rapidly. Diagnosis: ELISA is the test of choice, and monoclonal antibody is used to increase specificity; passage in swine tissue culture may often be required. Control: Any suspected outbreak should be reported to the proper authorities. Trichinellosis: Introduction (Trichinosis) Trichinellosis is a parasitic disease of public health importance caused by the nematode Trichinella spiralis . Human infections are established by consumption of insufficiently cooked infected meat, usually pork or bear, although other species have been implicated. Most mammals are susceptible. Etiology and Epidemiology: Trichinella spp are considered to be a complex of five species, with eight genotypes (T1 to T8) that have been identified by DNA analysis. Trichinella spiralis (T1) is the most common species affecting man and domestic animals in most temperate regions; it has high infectivity for pigs and rodents and low resistance to freezing. The other species include T nativa (T2)—found in arctic carnivores, with low infectivity for rats and pigs and resistant to freezing; T nelsoni (T7)— found primarily in wild carnivores in the southern hemisphere, including Africa, with low infectivity for rats and pigs and relatively low virulence; T pseudospiralis (T4)—lacks the cyst in muscle and is primarily a parasite of birds; T britovi (T3) —recently described in southern Europe and similar to T nelsoni in biologic characteristics. Infection occurs by ingestion of larvae encysted in muscle. The cyst wall is digested in the stomach, and the liberated larvae penetrate into the duodenal and jejunal mucosa. Within ~4 days, the larvae develop into sexually mature adults. After mating, the females (3-4 mm) penetrate deeper into the mucosa and discharge living larvae (up to 1,500) over 4-16 wk. After reproduction, the adult worms die and usually are digested. The young larvae (0.1 mm) migrate into the lymphatics and are carried via the portal system to the peripheral circulation and reach striated muscle where they penetrate individual muscle cells. They grow rapidly (to 1 mm) and begin to coil within the cell, usually one per cell. Capsule formation begins ~15 days after infection and is completed by 4-8 wk, at which time the larvae are infective. The cell degenerates as the larva grows, and then calcification occurs (at different rates in various hosts). Larvae may remain viable in the cysts for years, and their development continues only if ingested by another suitable host. The diaphragm, tongue, masseter, and intercostal muscles are among those most heavily involved in pigs.

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If larvae pass through the intestine and are eliminated in the feces before maturation, they are infective to other animals. Clinical Findings and Diagnosis: Most infections in domestic and wild animals go undiagnosed. Microscopical examination of a muscle biopsy sample (usually tongue) may confirm but not necessarily rule out trichinellosis. Control: Treatment is generally impractical in animals. Freezing pork at an appropriate temperature for an appropriate time is also effective (5°F [-15°C] for 20 days, -9.4°F [-23°C] for 10 days, or -22°F [-30°C] for 6 days). Freezing cannot be relied upon to kill trichinae in meat other than pork. Bluetongue: Introduction Etiology and Transmission: Bluetongue virus is the prototype virus of the genus Orbivirus , family Reoviridae. The distribution of the disease is limited by the culicoid insect vector that serves as the principal means of transmission between ruminant species. The viruses are biologically transmitted between ruminants by the biting midge Culicoides variipennis sonorensis , in the USA. Cattle develop prolonged viremias lasting for as long as 70-90 days. The viruses have an affinity for RBC and survive in the infected cattle until the cells are catabolized. Thus, cattle serve as reservoirs for the virus. Semen that contains RBC or WBC infected with bluetongue virus may infect susceptible cattle. Clinical Findings: The usual incubation period in sheep is 5-10 days. In chronological sequence of appearance, clinical signs include dyspnea with panting; hyperemia of the lips, muzzle, and ears; pyrexia (reaching 107.5°F [42°C]); depression; and inflammation, erosions, and ulceration of the oral mucous membranes, particularly the dental pad. Other signs include swollen cyanotic tongue, lameness due to coronitis and widespread muscle necrosis, torticollis, vomiting, pneumonia, conjunctivitis, and alopecia. Cattle more commonly have inapparent infections. The rare clinical case in cattle is characterized by vesicular and ulcerative lesions in the oral cavity, hyperesthesia, and a vesicular and ulcerative dermatitis. These lesions are mediated by an IgE hypersensitivity reaction. The malformations include hydranencephaly or porencephaly, which results in ataxia and blindness at birth. Diagnosis: Clinical signs are presumptive, and confirmation is based on identification of virus by isolation in embryonated chicken eggs, susceptible sheep, or cell cultures, or by polymerase chain reaction (PCR) technology. Bluetongue viremia is associated with RBC, and the virus can coexist with high neutralizing antibody titers. Affected sheep have increased CK levels, which often appear before signs of stiffness and are associated with muscle necrosis. On necropsy, lesions include mucosal erosions and ulceration, coronitis, hemorrhage in the pulmonary aorta, and necrosis of the striated muscles. Prevention and Control: Vaccines are widely used only in southern Africa. The modified live virus vaccines should not be used during the vector seasons because the culicoid vectors may pick up the vaccine virus and transmit it to other animals. There is mounting evidence that vaccine viruses may reassort with field strains, giving rise to new virus strains. Pregnant ewes should not be vaccinated during the first 100 days of gestation; otherwise, fetal malformations may occur. Passive immunity in lambs may last 4-6 mo. Control of vectors by using ear tags with insecticides, controlling water levels by raising or lowering the levels in lagoons every week, or moving animals into barns during the evening hours tends to lower the risk of culicoid exposure and subsequent bluetongue infection. Bovine Leukosis: Introduction (Lymphosarcoma, Malignant lymphoma, Leukemia) The term leukosis indicates a malignant proliferation of leukocyte-forming tissue. Because lymphoid tumors predominate in cattle, lymphosarcoma and malignant lymphoma are synonymous with bovine leukosis. Sometimes, the disease is called leukemia, but the presence of malignant cells in blood is not a consistent finding. Four clinicopathologic syndromes are recognized: calf, thymic, skin, and adult. The first three forms are called sporadic leukosis because there is no evidence that they are contagious. The adult form, also known as enzootic leukosis, is caused by the bovine leukosis virus (BLV). Sporadic leukosis occurs worldwide, whereas the geographic distribution of enzootic leukosis is directly related to prevalence of BLV. Transmission, Epidemiology, and Pathogenesis: Transmission of BLV occurs primarily by transfer of blood lymphocytes between animals. Insects may act as mechanical vectors of blood, but trauma, use of common bleeding needles, and surgical procedures probably are more common mechanisms of transmission. BLV can be transmitted to fetuses in utero, but usually <10% of calves from infected dams carry the virus at birth. Most BLV infections are asymptomatic and can be recognized only by a serological test that detects viral-specific antibody. The animal becomes seropositive 4-12 wk after exposure. Clinical Findings:
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In the calf form of leukosis, which affects animals <6 mo old, generalized lymphadenopathy and widespread tumor metastasis involve most organ systems and bone marrow. The thymic form typically occurs in animals 6-8 mo old. The tumor is usually confined to the thymus and results in a diffuse swelling of the ventral neck. Neoplastic tissue may also extend into the thorax, and metastasis to local lymph nodes is not uncommon. Lesions posterior to the diaphragm are uncommon. Skin leukosis, the only nonfatal lymphoid tumor in cattle, is seen in young adults. The superficial cutaneous tumors are present only a few weeks and, after the lesions regress, recurrence is rare.

Enzootic leukosis is a disease of mature cattle, and most cases occur in animals that are 4-8 yr old. The tissues most commonly affected include lymph nodes, abomasum, heart, spleen, kidneys, uterus, spinal meninges, and retrobulbar lymphatic tissue. Diagnosis: A presumptive diagnosis of leukosis can be made if there is clinical evidence of lymphadenopathy or tumor in a commonly affected tissue. Sometimes, leukemia can be demonstrated in the calf form, but thymic and skin cases are usually aleukemic. The serological test is not appropriate for calf, thymic, and skin leukosis, because the sporadic forms are not caused by BLV. Control: There is no treatment for leukosis or for BLV infection in individual animals. Virus can be eliminated from a herd if all cattle are tested serologically at 2- to 3-mo intervals, and positive animals removed immediately. Caprine Arthritis And Encephalitis: Introduction Caprine arthritis and encephalitis (CAE) virus infection is manifested clinically as polyarthritis in adult goats and less commonly as progressive paresis (leukoencephalomyelitis) in kids. Subclinical or clinical interstitial pneumonia, indurative mastitis (“hard udder”), and chronic wasting have also been attributed to infection with this virus. Most CAE virus infections, however, are subclinical. Infection with the CAE virus decreases the lifetime productivity of dairy goats and is a barrier to exportation of goats from North America. Under natural conditions, the CAE virus appears to be host-specific. In countries such as Canada, Norway, Switzerland, France, and the USA, seroprevalence of CAE virus is >65%. Etiology, Epidemiology, and Pathogenesis: The CAE virus is an enveloped, single-stranded RNA lentivirus in the family Retroviridae. Other lentiviruses include the progressive pneumonia virus of sheep, the equine infectious anemia virus, and the feline and human immunodeficiency viruses. The infection is widespread in dairy goat breeds but uncommon in meat- and fiber-producing goats. This has been attributed to a heritable predisposition to infection in dairy breeds. The chief mode of spread of CAE is through ingestion of virus-infected goat colostrum or milk by kids. The feeding of pooled colostrum or milk to kids is a particularly risky practice, because a few infected does will spread the virus to a large number of kids. The pathogenesis of CAE is not fully understood. Virus-infected macrophages present in colostrum and milk are taken up intact through the gut mucosa. Infection is subsequently spread throughout the body via infected mononuclear cells. Infection induces a strong humoral and cell-mediated immune response, but neither is protective. Clinical Findings: Arthritis is the syndrome exhibited by adult goats infected with the CAE virus. Clinical signs include joint capsule distension and varying degrees of lameness. The carpal joints are most frequently involved. The onset of arthritis may be sudden or insidious, but the clinical course is always progressive. Affected goats lose condition and usually have poor hair coats. Encephalomyelitis is generally seen in kids 2-4 mo old but has been described in older kids and adult goats. Affected kids initially exhibit lameness, ataxia, and hindlimb placing deficits.

Hypertonia and hyperreflexia are also common. Over time, signs progress to paraparesis or tetraparesis and paralysis. Depression, head tilt, circling, opisthotonos, torticollis, and paddling have also been seen in affected goats. The “hard udder” syndrome attributed to CAE virus infection is characterized by a firm, swollen mammary gland and agalactia at the time of parturition. Milk quality is usually unaffected. Lesions: Pathologic lesions of CAE virus infection are generally described as lymhoproliferative with degenerative mononuclear cell infiltration. Lesions in joints are characterized by thickening of the joint capsule and marked proliferation of synovial
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villi. In chronic cases, soft-tissue calcification involving joint capsules, tendon sheaths, and bursae is not uncommon. Severe cartilaginous destruction, rupture of ligaments and tendons, and periarticular osteophyte formation have also been described in advanced cases. Microscopic features of articular lesions include synovial cell hyperplasia, subsynovial mononuclear cell infiltration, villous hypertrophy, synovial edema, and synovial necrosis. On gross examination, lungs of affected goats are firm and gray-pink with multiple, small, white foci, and do not collapse. The bronchial lymph nodes are invariably enlarged. Histological findings include chronic interstitial pneumonia with mononuclear cell infiltration in alveolar septae and in perivascular and peribronchial regions. Diagnosis: A presumptive diagnosis can be based on clinical signs and history. Traumatic arthritis, and infectious arthritis caused by Mycoplasma spp , are differential diagnoses for arthritis induced by CAE virus. Differential diagnoses for the progressive paresis and paralysis exhibited by young kids should include enzootic ataxia, spinal cord abscess, cerebrospinal nematodiasis, spinal cord trauma, and congenital anomalies of the spinal cord and vertebral column. If neurologic examination indicates brain involvement, polioencephalomalacia, listeriosis, and rabies should be considered as possible causes. The pulmonary form of caseous lymphadenitis may have a similar clinical presentation to the pulmonary form of CAE. Serologic tests available for diagnosis are the agar gel immunodiffusion (AGID) and ELISA. In general, the ELISA is more sensitive than the AGID, but the latter test is more widely available in North America. Treatment and Control: There are no specific treatments for any of the clinical syndromes associated with CAE virus infection. However, supportive treatments may benefit individual goats. The condition of goats with the arthritic form of CAE may be improved with regular foot trimming, use of additional bedding, and administration of nonsteroidal anti-inflammatory drugs such as phenylbutazone or aspirin. Goats with encephalomyelitis can be maintained for weeks with good nursing care. Antimicrobial therapy is indicated to treat secondary bacterial infections that may complicate the interstitial pneumonia or indurative mastitis components of CAE virus infection. Colisepticemia: Introduction (Septicemic colibacillosis, Septicemic disease) Septicemia caused by Escherichia coli is a common diseases of calves, and to a lesser extent lambs, <1 wk old. It may present with signs of acute septicemia or as a chronic bacteremia with localization. Etiology and Epidemiology: Colisepticemia occurs during the first week of life, most commonly between 2 and 5 days of age. Chronic disease with localization can occur up to 2 wk of age. The disease is usually sporadic and is more common in dairy than beef calves. Transmission and Pathogenesis: Invasion occurs primarily through the nasal and oropharyngeal mucosa but can also occur across the intestine or via the umbilicus and umbilical veins. There is a period of subclinical bacteremia which, with virulent strains, is followed by rapid development of septicemia and death from endotoxemic shock. A more prolonged course, with localization of infection, polyarthritis, meningitis, and less commonly uveitis and nephritis, occurs with less virulent strains. Chronic disease also occurs in calves that have acquired marginal levels of circulating immunoglobulin. In groups of calves, transmission is by direct nose-to-nose contact, urinary and respiratory aerosols, or as the result of navel-sucking or fecal-oral contact. Clinical Findings and Diagnosis: In the acute disease, the clinical course is short (3-8 hr), and signs are related to the development of septic shock. Pyrexia is not prominent, and the rectal temperature may be subnormal. Listlessness and an early loss of interest in sucking are followed by depression, poor response to external stimuli, collapse, recumbency, and coma. There is tachycardia, a poor pulse pressure, and a prolonged capillary refill time. The feces are loose and mucoid, but severe diarrhea is not seen in uncomplicated cases. Mortality approaches 100%. With a more prolonged clinical course, the infection may localize. Polyarthritis and meningitis are common; tremor, hyperesthesia, opisthotonos, and convulsions are seen occasionally, but stupor and coma are more common. A moderate but significant leukocytosis and neutrophilia are seen early, but a marked leukopenia is present in the terminal stages. There are increased inflammatory cells and protein in joint fluid, and the CSF shows pleocytosis and an increased protein concentration; organisms may be evident on microscopical examination. As with colisepticemia, the primary determinant of these infections is a failure of passive transfer of immunoglobulins. The diagnosis is based on history and clinical findings, demonstration of a severe deficiency of circulating IgG, and ultimately, demonstration of the organism in the blood or tissues. Zinc sulfate or total protein estimation can be used for rapid estimation of IgG ( Nutritional Requirements , Beef Cattle). Treatment: Treatment requires aggressive use of antibiotics. Because there is no time for sensitivity testing, the initial choice should be a bactericidal drug (eg, an aminoglycoside) that has a high probability of efficacy against gram-negative organisms. Antibacterial therapy should be coupled with aggressive fluid, drug, and other therapy for endotoxic shock. Control and Prevention:
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Calves that acquire adequate concentrations of immunoglobulin from colostrum are resistant to colisepticemia. Therefore, prevention depends primarily on developing management practices that ensure an adequate and early intake of colostrum. Where natural colostrum is not available for a newborn calf, commercial colostrum substitutes containing 25 g IgG will provide sufficient immunoglobulin for protection against colisepticemia if fed early in the absorptive period. Plasma containing at least 4 g and preferably 8 g IgG, administered parenterally, will provide some protection for older calves that have not been fed colostrum and are unable to absorb immunoglobulins from the intestine. To minimize transmission, calves reared indoors should be in separate pens (without contact) or reared in calf hutches. Haemophilus Somnus Disease complex: Introduction (Thrombotic meningoencephalitis, TME) Haemophilus somnus can cause an acute, usually fatal septicemic disease that can involve the nervous, musculoskeletal, circulatory, and respiratory systems, either singly or together. The reproductive system is often affected but usually without the other systems being clinically involved. The disease may be characterized by fever, severe depression, ataxia, weakness, blindness, coma, and death within several hours to several days. It occurs sporadically in individual beef and dairy cattle and is found nearly worldwide. Etiology: Haemophilus somnus is a gram-negative, nonmotile, nonsporeforming, pleomorphic coccobacillus that requires an enriched medium and a microaerophilic atmosphere for culture. Transmission, Epidemiology, and Pathogenesis: The organism may colonize the respiratory tract, presumably after inhalation, and is frequently found in urine. Several disease syndromes caused by H somnus have been recognized, including thrombomeningoencephalitis (TME [probably the most commonly recognized but still relatively infrequent disease]), fibrinopurulent bronchopneumonia (frequent in cattle diagnosed with shipping fever in some regions), fibrinous pleuritis, and polyarthritis. Myocardial and skeletal muscle necrosis occur. Suppurative vaginitis, cervicitis, and endometritis have been documented in cows infected experimentally and naturally after breeding, and the organism is a cause of sporadic abortion. Strains of H somnus that cause disease adhere to the endothelium of vessels, resulting in contraction, exposure of collagen, platelet adhesion, and thrombosis. TME results when this occurs in the brain and associated membranes, after invasion of the organism into the bloodstream of susceptible cattle. Strains may adhere to endothelium in vessels of the pleura, myocardium, synovium, or a variety of other tissues and produce inflammation in those sites (eg, infections of the larynx and middle ear have been recorded). The susceptibility of individual animals and variations in the preference of strains of the organism for vessels in different tissues may be important in the development of the form of disease, but the mechanisms involved are incompletely understood. Reproductive problems may not necessarily be preceded by bacteremia, but the pathogenesis is poorly defined. Clinical Findings: A fever as high as 108°F (42°C) is often the first sign of disease; however, this usually falls to normal or subnormal within hours. Other findings are determined by the system(s) involved and may include rapid respiration, stiffness, knuckling at the fetlocks, severe depression, ataxia, paralysis, and opisthotonos, followed by coma and death within several hours. Affected animals may be blind, and retinal hemorrhages with gray foci of retinal necrosis are sometimes seen. Signs such as hypersensitivity, convulsions, excitement, nystagmus, and circling occur inconsistently and may be related to the regions of the CNS affected in the course of disease development. Occasionally, animals are found dead, indicating a rapidly fatal course. A marked change in the total and differential WBC count is common; leukopenia and neutropenia occur in severe, usually acute, fatal disease, while neutrophilia may be present in less severe disease. In TME, the total cell count of the CSF is markedly increased, and neutrophils predominate. Lesions: The lesions are characterized by vascular thrombosis and infarction of the surrounding tissue. Randomly distributed red to brown foci of necrosis with hemorrhage on the surface and cut sections of the brain and spinal cord, retina, skeletal muscle, myocardium, kidney, intestine, and spleen are characteristic. Blood-borne infections are not usually associated with abortion. A fatal endometritis may follow abortion and, as in other tissues, lesions in the uterus and placenta usually consist of a vasculitis and thrombosis. Diagnosis: Presumptive diagnosis is based on clinical signs and examination and culture of the affected tissues. Treatment often interferes with recovery of the organism. Differential diagnoses of TME include polioencephalomalacia, hypovitaminosis A, acute lead poisoning, rabies, pseudorabies, and listerial meningoencephalitis. Treatment and Control:

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Clinically affected animals should be separated and treated immediately with penicillin and streptomycin or with oxytetracycline. Treatment is most effective in the early stages of disease. Once the animal becomes recumbent, the prognosis is grave. Malignant Catarrhal Fever: Introduction (Malignant head catarrh, Snotsiekte, Catarrhal fever, Gangrenous coryza) Malignant catarrhal fever (MCF) is an acute, sporadic, infectious disease of cattle and some other Bovidae and Cervidae characterized by low morbidity and extremely high mortality, although on occasions, morbidity can be high, particularly in susceptible species such as Pere David's deer and Bali cattle. Etiology: While MCF is a single clinicopathologic entity, there are at least two distinct but related agents that can cause the disease naturally. One, alcelaphine herpesvirus 1 (AHV-1), which is carried inapparently by wildebeest ( Connochaetes taurinus and C gnou ), is prevalent in Africa and in zoological parks and is responsible for “wildebeest-derived” MCF (WDMCF). The other principal cause is the “sheep-associated” agent of MCF. While the sheep-associated agent has not been isolated, molecular and serologic evidence indicate it is similar to AHV-1. It has been designated ovine herpesvirus 2 (OHV-2). It occurs worldwide in both wild and domestic sheep and goat species, usually without causing disease. Transmission and Epidemiology: MCF usually occurs in adults. Susceptibility to MCF among deer varies: wapiti and red deer are much more susceptible than cattle; Pere David's, sika, and white-tailed deer are highly susceptible. Disease has not been reported in fallow deer, which suggests they are resistant. Susceptible ruminants are “end hosts,” which develop clinical MCF after an incubation period of 3 wk to 6 mo. In such animals, the virus is cell-associated, and horizontal transmission is believed to be rare. Pathogenesis: The most plausible current hypothesis is that development of the disease hinges on infection of immunoregulatory, large, granular lymphocytes, with “natural-killer” (NK) activity. The normal MCF reaction has the characteristics of a Tlymphocyte hyperplasia, a polyclonal response resulting from deregulation of the T lymphocytes. It is suggested that the necrotizing process of the terminal phase of the disease is an autoimmune phenomenon arising through the expression of NK-like activity of certain immune system cells. Clinical Findings: MCF can take peracute, acute (“head and eye”), subacute, or chronic forms. Deer often have the peracute disease with sudden death, usually preceded by evidence of disseminated intravascular coagulation. Dyspnea also may be present. Acute disease is the most common in cattle and wild Bovidae. This form is characterized by fever, depression, enlarged lymph nodes, serous nasal and ocular discharges, erosions of the buccal papillae, ophthalmia, and diarrhea (sometimes hemorrhagic). Additional signs include inflammatory and erosive lesions in the mucosa of the upper respiratory tract that lead to profuse mucopurulent nasal discharge with encrustation of the muzzle, ulceration of the oral mucosa, salivation, and mucopurulent conjunctivitis with corneal opacity that begins at the corneoscleral junction and progresses centripetally. Some animals show CNS signs such as excitability, hyperesthesia, and muscular tremors. Occasionally, these may progress to convulsions or an aggressiveness suggestive of rabies. The course of the “head and eye” form can last for up to 2 wk. In chronic MCF, inanition develops. Recovery is rare. The hemogram may show lymphocytosis followed by lymphopenia. Lesions: Lesions are widespread and usually affect all organs, but their severity and nature vary considerably. The principal changes that characterize MCF are epithelial necrosis (GI, respiratory, or urinary) associated with mucosal or dermal lymphoid inflammation, lymphoproliferation, interstitial infiltration of nonlymphoid tissues, and vasculitis. In deer, hemorrhage into the lumen of the ileum, cecum, and colon may be prominent, together with ecchymoses in the colonic serosa. Most lymph nodes are hyperplastic and the paracortex is prominent, but hemorrhage and necrosis may occur terminally. A prominent feature is interstitial infiltration of organs by lymphocytes, especially heart, liver, adrenal gland, meninges, CNS perivascular spaces, and kidney; in the kidney, it can be detected grossly as white, raised foci under the capsule. The rete mirabilis is a tissue of choice to demonstrate vascular lesions. Diagnosis: Confirmation relies on histologic examination, especially the demonstration of multisystemic lymphoid infiltration, disseminated vasculitis, and degenerative epithelial lesions. The polymerase chain reaction (PCR) can be used to detect and amplify MCF virus-specific DNA segments in tissues of animals clinically infected with MCF or in virus carriers. It is the most sensitive test for detecting asymptomatic virus carriers and, when properly applied, is highly specific. Differential diagnoses include rinderpest, bluetongue, vesicular diseases, East Coast cattle fever ( Theileria parva ), infectious bovine rhinotracheitis, bovine viral diarrhea-mucosal disease, shipping fever, and when there are nervous signs, rabies and the tickborne encephalitides. When farmed red deer are affected, yersiniosis must be excluded. Treatment and Control: Survival is rare. Antibiotics or sulfonamides to control secondary bacterial infection and supportive therapy (fluids) may be worthwhile in valuable animals, but if these survive, they will likely remain virus carriers.
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Paratuberculosis: Introduction (Johne's disease) Paratuberculosis is a chronic, contagious enteritis characterized by persistent and progressive diarrhea, weight loss, debilitation, and eventually death. Etiology and Pathogenesis: The causative organism is Mycobacterium avium paratuberculosis , formerly known as M paratuberculosis or M johnei. The organism is quite resistant and can survive on pasture for >1 yr, but sunlight, alkaline soils, and drying reduce its survival rate. It is shed in large numbers in feces of infected animals, and infection is acquired by ingestion of contaminated feed and water. Introduction of the disease into a clean herd is usually by subclinically infected carriers. The organism can also be present in colostrum and milk of infected cows, and intrauterine infections have also been described. After ingestion, the bacteria infect macrophages in the mucosa of the lower small intestine and in associated lymph nodes. Most animals will eliminate infection by an early cell-mediated immune response that encourages microbicidal activity in macrophages. In susceptible animals, the organisms multiply and provoke a chronic enteritis that leads to clinical disease. Clinical Findings: The disease is characterized by weight loss and diarrhea, but initial signs are variable and often vague. Diarrhea may be intermittent; it is typically thick, does not contain blood, mucus, or epithelial debris; and is passed without tenesmus. Over weeks or months, the diarrhea becomes more severe, there is further weight loss, coat color may fade, and ventral and intermandibular edema may develop. In dairy cattle, milk yield may drop or fail to reach expected levels. Animals are alert, and temperature and appetite are usually normal, although thirst may be increased. The disease is progressive and ultimately terminates in emaciation and death. Most cases occur in cattle 2-6 yr old. The protein-losing enteropathy leads to low concentrations of total protein and albumin in plasma, although gamma globulin levels are normal. In infected groups, the mortality rate may be only ~1%, but up to 50% of animals may have subclinical infection with associated production losses. The disease in sheep and goats is similar, but diarrhea is not a common feature, and advanced cases may shed wool easily. In deer, the course of the disease can be more rapid. Lesions: Some strains of the organism cause yellow-orange mucosal pigmentation. Lesions may extend proximally and distally to the jejunum and colon. Sheep, goats, and deer sometimes develop foci of caseation with calcification in the intestinal wall and lymph nodes. Diagnosis: There is no single, good test for paratuberculosis, and a combination of tests is often used. Diagnosis for a group of animals is easier than in an individual. Fecal culture is highly specific but not highly sensitive because animals may shed organisms intermittently, and repeated testing may be necessary to confirm infection. ELISA has quite high sensitivity, and specificity is improved by pre-absorbance of sera with M phlei . Necropsy with histopathologic examination of intestine and lymph nodes is usually effective for diagnosis. Control: No satisfactory treatment is known. Control requires good sanitation and management. Herds with confirmed cases should be tested to determine the extent of infection, and positive animals sent to slaughter. Calfhood (<1 mo of age) vaccination can be effective in reducing disease incidence but does not eliminate infection. Pasteurellosis of Sheep And Goats: Introduction Pasteurella organisms are nonmotile, nonsporeforming, aerobic, fermentative, gram-negative coccobacilli. Pasteurella haemolytica is the species most often associated with disease. It is the primary agent involved in respiratory disease, septicemia, arthritis, meningitis, and mastitis, and it may also be an important secondary invader in ruminant respiratory diseases of ruminants. Sixteen serotypes of P haemolytica are currently recognized on the basis of capsular antigens; 12 of the serotypes are classified under biotype A, and 4 under biotype T. Biotype A is most commonly associated with pneumonic pasteurellosis ( Pasteurella Pneumonia), while biotype T mainly causes septicemia and systemic pasteurellosis (see Systemic Pasteurellosis) in young, weaned sheep. Pneumonic pasteurellosis can also be caused primarily or secondarily by P multocida in sheep and goats, and outbreaks worldwide lead to high mortality and great economic loss. Both P haemolytica biotypes and P multocida are common commensal organisms of the tonsils and nasopharynx of healthy sheep and goats. Systemic Pasteurellosis The systemic form of pasteurellosis is caused by P haemolytica biotype T. Systemic pasteurellosis results when the organism moves from the tonsils to the lungs and passes into the blood. This results in septicemia or localization of the infection in one or more tissue such as the joints, udder, meninges, or lungs. Systemic pasteurellosis is most common in young, weaned sheep (~6 mo old) during the late fall and winter after transport or a sudden feed change, but it can occur in sheep of any age throughout the year. Sheep with septicemia often die quickly without premonitory signs. In some animals,
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pyrexia, dullness or coma, recumbency, dyspnea, and a frothy discharge from the mouth may be noted before death. Diagnosis is often based on clinical findings of sudden death, isolation of P haemolytica biotype T from a range of tissues, and gross and histopathologic findings. Lesions include subcutaneous hemorrhage; epithelial necrosis of the tongue, pharynx, esophagus, or occasionally the abomasum and intestine; enlargement of tonsils and retropharyngeal lymph nodes; and peracute, multifocal, embolic, necrotizing lesions in the lung and liver associated with bacteria of a consistent morphology. Rinderpest: Introduction (Cattle plague) Rinderpest is a disease of cloven-hoofed animals characterized by fever, necrotic stomatitis, gastroenteritis, lymphoid necrosis, and high mortality. Etiology and Epidemiology: The cause is a morbillivirus closely related to the viruses of peste des petits ruminants ( Peste Des Petits Ruminants: Introduction), canine distemper ( Canine Distemper: Introduction), and measles. Sera from recovered or vaccinated cattle cross-react with all rinderpest viral strains in neutralization tests, but minor antigenic differences have been demonstrated. The virus is fragile and rapidly inactivated by heat and light but remains viable for long periods in chilled or frozen tissues. In epidemic form, rinderpest is the most lethal plague known in cattle. In endemic areas, young cattle become infected after maternal immunity disappears and before vaccine immunity begins, with possible auxiliary cycles in sheep, goats, and wild ungulates. In epidemic areas, the virus infects most susceptible animals and tends to limit itself unless the population is large enough to support endemicity. In endemic areas, morbidity is low and clinical signs are often mild; in epidemics, morbidity is often 100% and mortality up to 90%. Transmission and Pathogenesis: The virus is present in small amounts in nasal secretions of affected animals 1-2 days before fever; levels are high in secretions and excretions during the first week of clinical disease and decrease rapidly as animals develop antibody and begin to recover. Transmission requires direct or close indirect contact; infection is via the nasopharynx. There is no carrier state; the virus maintains itself by continuous transmission among susceptible animals. After primary growth in lymph nodes associated with the nasopharynx, the virus proliferates throughout the lymphoid tissue and spreads via the blood to the mucosae of the GI and upper respiratory tracts. Tissue damage is caused by viral cytopathology. Clinical Findings: An incubation period of 3-15 days is followed by fever, anorexia, and depression. Oculonasal discharge develops 1-2 days later. Within 2-3 days, pinpoint necrotic lesions, which rapidly enlarge to form cheesy plaques, appear on the gums, buccal mucosa, and tongue. The hard and soft palates are often affected.

The oculonasal discharge becomes mucopurulent, and the muzzle becomes dry and cracked. Diarrhea, the final clinical sign, may be watery and contain blood, mucus, and mucous membrane. Animals show severe abdominal pain, thirst, and dyspnea and may die from dehydration. Convalescence is prolonged and may be complicated by concurrent infections due to immunosuppression. Lesions: Gross pathological changes are evident throughout the GI and upper respiratory tracts, either as areas of necrosis and erosion, or congestion and hemorrhage, the latter causing classical “zebra-striping” in the rectum. Lymph nodes may be enlarged and edematous, with white necrotic foci in the Peyer's patches. Histological examination reveals lymphoid and epithelial necrosis with viral syncytia and intracytoplasmic inclusions. Diagnosis: In areas where the disease is uncommon or absent, laboratory tests must be used to differentiate rinderpest from bovine viral diarrhea in particular, as well as East Coast fever, foot-and-mouth disease, infectious bovine rhinotracheitis, and malignant catarrhal fever. ELISA, for detecting viral antigens or serum antibodies, is also a valuable diagnostic test. Control: Treatment usually is not attempted, but supportive nursing care with fluid and antibiotics may aid recovery of valuable animals. Active immunity is usually lifelong; maternal immunity lasts 6-11 mo. Control in endemic areas is by immunization of all cattle and domestic buffalo >1 yr old with attenuated cell culture vaccine. Tick-borne Fever: Introduction Tick-borne fever (TBF) is a febrile disease of domestic and free-living ruminants in the temperate regions of Europe. It is transmitted by the hard tick Ixodes ricinus. The main hosts are sheep and cattle, but goats and deer are also susceptible. Etiology: The causative agent is now classified as a member of the order Rickettsiales in the genus Ehrlichia or Cytoecetes as Ehrlichia (Cytoecetes) phagocytophila ).
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The organism infects eosinophils, neutrophils, and monocytes, in that order. Cytoplasmic inclusions are visible as grayish blue bodies in Giemsa-stained blood smears and may contain one or more rickettsial particles of variable size and shape. The disease is transmitted by the tick I ricinus . Infections do not appear to pass from the adult female to the larva via the egg. The rickettsiae can survive in infected ticks for long periods and, because I ricinus can survive unfed for >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:
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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 <1 wk. This may be accompanied by serous nasal discharge, mucopurulent ocular discharge, and anorexia. GI and respiratory signs may follow and are usually complicated by secondary bacterial infections. An acute encephalomyelitis may occur in association with or immediately after the systemic disease, or in the absence of systemic manifestations. Hyperkeratosis of the footpads (“hardpad” disease) and epithelium of the nasal plane may be seen. Neurologic signs are frequently seen in those dogs with hyperkeratosis. CNS signs include 1) localized involuntary twitching of a muscle or group of muscles (myoclonus, chorea, flexor spasm, hyperkinesia), such as in the leg or facial muscles; 2) paresis or paralysis, often beginning in the hindlimbs evident as ataxia, followed by ascending paresis and paralysis; and 3) convulsions characterized by salivation and chewing movements of the jaw (petit mal, “chewing-gum fits”). The seizures become more frequent and severe, and the dog may then fall on its side and paddle its legs; involuntary urination and defecation (grand mal seizure, epileptiform convulsion) often occur. A dog may exhibit any or all of these neurologic signs in addition to others in the course of the disease. Infection may be mild and inapparent or lead to severe disease manifest by most of the above signs. The course of the systemic disease may be as short as 10 days, but the onset of neurologic signs may be delayed for several weeks or months. Chronic distemper encephalitis (old dog encephalitis, [ODE]), a condition often marked by ataxia, compulsive movements such as head pressing or continual pacing, and incoordinated hypermetria, may occur in adult dogs without a history of signs related to systemic canine distemper. Convulsions and neuromuscular twitching (chorea) do not seem to occur with ODE. Although canine distemper antigen has been detected in the brain of dogs with ODE by fluorescent antibody staining, dogs with ODE are not infectious and replication-competent virus has not been isolated. The disease is caused by an inflammatory reaction associated with persistent canine distemper virus infection in the CNS. Lesions: Thymic atrophy is a consistent postmortem finding in young puppies. Hyperkeratosis of the nose and foot pads may be present. Depending on the degree of secondary bacterial infection, bronchopneumonia, enteritis, and skin pustules may also be present. Histologically, canine distemper virus produces necrosis of lymphatic tissues, interstitial pneumonia, and cytoplasmic and intranuclear inclusion bodies in respiratory, urinary, and GI epithelium. Lesions found in the brain of dogs with neurologic complications include neuronal degeneration, gliosis, demyelination, perivascular cuffing, nonsuppurative leptomeningitis, and intranuclear inclusion bodies predominately within glial cells. Diagnosis: Distemper should be considered in the diagnosis of any febrile condition in puppies with multisystemic manifestations. While the typical clinical case is not difficult to diagnose, the characteristic signs sometimes fail to appear until late in the disease. The clinical picture may be modified by concurrent toxoplasmosis, neosporosis, coccidiosis, parasitoses, and numerous viral and bacterial infections. Distemper is sometimes confused with other systemic infections such as leptospirosis, infectious canine hepatitis, or Rocky Mountain spotted fever. Intoxicants such as lead or organophosphates can cause simultaneous GI or neurologic sequelae. A febrile catarrhal illness with neurologic sequelae justifies a clinical diagnosis of distemper. Treatment: Treatments are directed at limiting secondary bacterial invasion, supporting the fluid balance and overall well-being of the dog, and controlling nervous manifestations. No one treatment is specific or uniformly successful. Unfortunately, treatment for neurologic manifestations of distemper are unsuccessful. If the neurologic signs are progressive or severe, the owner should be appropriately advised. Prevention: Successful immunization of pups with canine distemper modified live virus (MLV) vaccines depends on the lack of interference by maternal antibody. To overcome this barrier, pups are vaccinated with MLV vaccine when 6 wk old and at 2- to 4-wk intervals until 16 wk old. Measles virus induces immunity to canine distemper virus in the presence of relatively greater levels of maternal distemper antibody. Feline Infectious Peritonitis And Pleuritis: Introduction (Feline coronaviral vasculitis) Feline infectious peritonitis (FIP) is a contagious viral disease of domestic and wild cats worldwide. It is immunologically mediated and induced by systemic infection with the feline coronavirus. The disease is progressive and manifests clinically as either an effusive (serositis or wet) or noneffusive (granulomatous or dry) form. A distinct clinical form of noneffusive FIP affecting only the eyes or brain (or both) may occur. Mortality, even with therapy, approaches 100%. Etiology: The etiologic agent of FIP is a coronavirus, FIPV; it is antigenically related to and serologically cross-reacts (by current ELISA and immunofluorescent antibody tests) with a subgroup of mammalian coronaviruses, including the transmissible gastroenteritis virus of swine, the human coronavirus 229-E, the canine coronavirus, and the feline enteric coronavirus. Feline Enteric Coronavirus: Introduction FIPV and the canine coronavirus are very closely related antigenically and may
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be host range mutants; some strains of canine coronavirus can induce an FIP-like disease in cats. FIPV is fairly stable in the environment and once dry can survive for several weeks. The virus is destroyed by most household disinfectants, particularly household bleach at a 1:32 dilution. Transmission, Epidemiology, and Pathogenesis: Most FIPV infections probably result from ingestion of the virus; however, aerosol transmission is also possible. Close contact with an infected cat or its excreta, most likely feces and saliva, is required for virus transmission. Transplacental transmission is suggested by the occasional observation of FIP in stillborn kittens, but the frequency with which this occurs is unknown. Many cats with FIP, perhaps 20-25% or more, are co-infected with leukemia virus (FeLV); FeLV potently suppress cell-mediated immunity, which is required for resistance to FIP. Cats of all ages and either sex can contract the disease, but incidence is highest in cats 6 mo to 2 yr old, decreased in cats 5-13 yr old, and increased in those 14-15 yr old. Kittens raised in infected colonies may contract the virus from their mothers or asymptomatic carriers when their maternal immunity wanes at 5-10 wk of age. These kittens typically may develop FIP weeks or months after they are placed in new homes. The prevalence of clinical FIP is relatively low, probably 1-2% or less in clinic populations. However, losses are often sporadic and unpredictable, and morbidity and mortality may be greatly increased, sometimes up to 35% or more in some breeding catteries and households with multiple cats. Generally, the morbidity rate in cattery-bred kittens does not exceed 10%. The prevalence of FIPV infection in the general cat population is difficult to determine because current serologic tests for detecting FIPV antibodies cannot discriminate between FIPV and other feline coronaviruses that do not produce disease and that may be more prevalent. About 5-12% of cats seropositive for coronavirus develop classical FIP. After ingestion of virus or aerosol exposure, FIPV initially replicates in tonsil or intestinal epithelium and then is transported via macrophages and monocytes to primary target organs such as liver, spleen, and visceral lymph nodes. The development of FIP, and the particular clinical form of disease (ie, effusive or noneffusive) depends on the intrinsic immune responses of the cat. Cats with a strong humoral immunity and a weak or absent cell-mediated immune response against FIPV develop a persistent viremia and effusive FIP. The effusive disease results from widespread formation and deposition of immune complexes in blood vessels and complement activation leading to vasculitis, vessel damage, and leakage of serum and protein into body cavities. Cats with partial cell-mediated immune responses along with humoral immunity develop the more chronic noneffusive FIP, which is characterized by immune-mediated (delayed hypersensitivity-like) granulomatous, frequently perivascular, lesions in abdominal viscera, lungs, eyes, and brain. Cats with strong cell-mediated immune responses with or without humoral responses either can completely recover or become persistently infected, asymptomatic carriers. Clinical Findings: The acute or primary infection often is asymptomatic, but in some cases, fever of unknown origin, conjunctivitis, and other upper respiratory signs and diarrhea may occur. This stage may last several days or weeks or longer before signs of effusive or noneffusive FIP develop. Cats with effusive FIP are often presented after the owner notices progressive distension of the abdomen due to ascites. About one-third of cats with effusive FIP have pleural involvement and dyspnea often accompanied by chronic fluctuating fever (39-41°C and lasting 2-5 wk), anorexia, weight loss, and depression. Cats with noneffusive FIP may have a history of vague illness, including chronic fever, malaise, weight loss, and occasionally major organ system failure (renal, hepatic). Overt ocular and CNS signs may occur simultaneously or independently. About 50% of all cats with noneffusive FIP have signs related to intra-abdominal involvement (kidney, liver, spleen, pancreas, lymph nodes); about 60% of cases exhibit either CNS or ocular signs, or both; and about 15% present with ocular signs only. Only 10-15% of noneffusive cases have lesions of the pleural cavity. Ocular disease may manifest as a bilateral anterior uveitis with iritis or iridocyclitis, hyphema, aqueous flare, hypopyon, or keratic precipitates in the anterior chamber. Posterior chamber involvement may include chorioretinitis with subretinal fluid exudation or hemorrhage and secondary bullous or linear retinal detachment. Fundic lesions may include perivascular cuffing, engorgement of retinal veins, and retinal hemorrhage. Involvement of the CNS in the noneffusive form may cause focal or diffuse lesions in the brain or spinal cord. About 40% of dry FIP cases have CNS signs occurring either singly (25%) or in combination with other organ involvement. Clinical signs are variable and may reflect primary spinal cord, cranial, or cerebellar disease. The most common neurologic signs, in order of decreasing frequency, are posterior incoordination and paresis progressing into a generalized ataxia, dorsal hyperesthesia, convulsions, and personality changes. Lesions: In classic effusive FIP, there is diffuse peritonitis or pleuritis (or both) characterized grossly by variable amounts of viscous abdominal or thoracic fluid, deposition of grey-white exudate, and disseminated necrotic plaques (0.5-3.0 mm) on the visceral and parietal peritoneum and/or pleura. Fibrinous adhesions, particularly between the liver and diaphragm and between loops of bowel, can occur in protracted cases; occasionally, the omentum may be contracted into the anterior abdomen as a thickened mass of fibrinous adhesions. Histologically, lesions are characterized by perivascular necrosis and fibrinonecrotizing or pyogranulomatous inflammation; FIPV particles are seen within macrophages at the periphery of lesions.
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Gross lesions in noneffusive FIP consist of multiple, gray-white, raised nodules (0.5-2 cm or larger) in kidneys, visceral lymph nodes, liver, intestines, lungs, eyes, and brain. Histologically, the lesions are perivascular granulomas or pyogranulomas with systemic vasculitis or thrombovasculitis. Ocular lesions may affect either anterior or posterior chambers causing anterior uveitis and iridocyclitis or chorioretinitis, retinitis, retinal hemorrhage and detachment, and optic neuritis. Lesions in the CNS affect the brain and spinal cord and can cause either focal granulomatous masses or more diffuse fibrinonecrotizing or pyogranulomatous meningitis and ependymitis. Obstructive hydrocephalus occasionally occurs when CSF flow is obstructed by inflammatory exudate. Diagnosis: Presumptive diagnosis of FIP is based on history, clinical signs, and results of laboratory tests. Diagnosis of effusive FIP is based largely on analysis of the characteristic exudate. The fluid typically is sterile, viscous or ropey, and yellow to straw-colored; it may contain fibrin strands, has a high specific gravity (1.017-1.047) and high protein content (5-12 g/dL), and is composed of variable amounts of mixed inflammatory cells (1,600 to 25,000/µL). Mixtures of neutrophils, lymphocytes, macrophages, and fewer Mesolithic cells in a granular, eosinophilic, proteinaceous background are seen on Wright's-stained smears. Protein determinations and electrophoresis of the exudate may be useful in diagnosis: gamma globulin >32% is reported to be 100% predictive of FIP, whereas an albumin content >48% or an albumin to globulin ratio > 0.81 reportedly is 100% predictive in ruling out FIP. About 50% of cats with effusive FIP (and up to 70% of cats with noneffusive FIP) have an increased total plasma protein (>7.8 g/dL), often with hyperglobulinemia (>4.6 g/dL) and a hypergammaglobulinemia. Serologic tests (ELISA, immunofluorescent antibody) that detect antibodies against coronaviral proteins are not specific for FIPV and also detect antibodies against feline enteric coronavirus. The coronavirus titer in cats with FIP is usually increased (1:100 to 1:3200); some cats with clinical FIP have no or very low titers. Noneffusive FIP is a greater diagnostic challenge. Serum protein abnormalities in debilitated cats with nonresponsive fever, weight loss, multisystemic signs (including ocular and CNS signs), and increased coronavirus titers are suggestive of noneffusive FIP. A thorough ophthalmic examination is indicated because nearly 40% of noneffusive cases have ocular lesions. Other ancillary laboratory tests may be helpful; clinical chemistries may indicate organ dysfunction in liver, kidney, or pancreas. In cases of neurologic disease with diffuse meningeal involvement, CSF analysis may show increased protein content (90 to 2,000 mg/dL) and increased numbers of cells (90 to 9,250 cells/µL), predominantly neutrophils. The most definitive antemortem diagnostic technique is laparotomy and organ punch biopsy of lesions with subsequent demonstration of typical histopathologic changes. FIP should be considered in the differential diagnosis of any condition that causes peritoneal or thoracic fluid accumulation and in any chronic wasting disease of cats. Effusive FIP with peritoneal involvement should be differentiated from ascites due to congestive heart failure or hypoproteinemia (renal and liver disease, glomerulonephritis, malabsorption, parasitism), bacterial peritonitis, pansteatitis, toxoplasmosis, tuberculosis, pregnancy, and trauma. Differential diagnosis of effusive FIP with pleural effusion includes cardiac insufficiency, neoplasia (lymphoma), pyothorax, chylothorax, cryptococcosis, lung lobe torsion, diaphragmatic hernia, and trauma (hemothorax). Differential diagnosis of noneffusive FIP includes neoplasia and other systemic infectious diseases such as toxoplasmosis, nocardiosis, actinomycosis, tuberculosis, and deep mycotic disease (cryptococcosis, coccidioidomycosis, histoplasmosis, blastomycosis). Treatment: There is no known treatment that can cure FIP once clinical signs arise. Although spontaneous remission in treated cats has been reported, it is uncommon. Most cats with clinical FIP die several weeks or months after diagnosis. Treatment with anti-inflammatory and immunosuppressive drugs, along with supportive care, can make the cat more comfortable; in some cats (probably ≤10%), therapy may extend survival time by several months. Treatment of FIP is best advised in cats that are in good physical condition, are still eating, have no neurologic signs, and that do not have concurrent FeLV-induced malignancy or bone marrow suppression. Conventional treatment of FIP using glucocorticoids and cytotoxic agents is aimed at suppressing inflammation and immune (particularly antibody) responses, thus decreasing the severity of the immune complex disease and the vasculitis. The most effective treatments are combinations of prednisolone and cyclophosphamide Because this cytotoxic therapy may suppress bone marrow cells, the hemogram should be monitored weekly, and the cat observed carefully for signs of sepsis. Supportive therapy for FIP is important and includes broad-spectrum antibiotics, adequate nutrition and fluid intake, and high doses of ascorbic acid (125-250 mg, b.i.d.). The use of low doses of aspirin (10 mg/kg every 48-72 hr) may be useful as an anti-inflammatory and possibly antithrombotic agent when used along with the steroids and cytotoxic agents. Prevention and Control: An intranasal, modified live virus vaccine to help prevent FIP is available. Because FIP in the general cat population is a relatively rare disease, the need to immunize individual pet cats that live mostly or entirely indoors is equivocal. Feline Leukemia Virus And Related Diseases: Introduction (Feline lymphoma and leukemia, Lymphosarcoma)

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Despite the widespread use of vaccines, feline leukemia virus (FeLV) remains one of the most important causes of morbidity and mortality in cats. It causes a variety of malignancies, but persistent infection can also cause severe immunosuppression and profound anemia. Etiology and Epidemiology: FeLV is a retrovirus in the family Oncovirinae. Other oncoviruses include feline sarcoma virus, mouse leukemia viruses, and two human T-lymphotropic viruses. Although oncogenesis is one of their more dramatic effects, oncoviruses cause many other diseases, including degenerative, proliferative, and immunological disorders. There are three main FeLV subgroups of clinical importance. Subgroup A viruses are found in all naturally infected cats. FeLV-A, the original, archetypical form of the virus, is efficiently transmitted among cats. FeLV-A viruses tend to be less pathogenic than viruses of the other subgroups, but some strains cause severe immunosuppression. Almost all naturally infected cats are originally infected by FeLV-A. Within the infected cat, FeLV-A is sometimes altered to produce FeLV-B and FeLV-C viruses. FeLV-B is found in ~50% of naturally infected cats, along with FeLV-A. The FeLV-A and FeLV-B together are more frequently associated with neoplastic diseases than is FeLV-A alone. FeLV-C viruses are isolated from only 1% of naturally infected cats, along with FeLV-A and sometimes both FeLV-A and FeLV-B. The presence of FeLV-C in an infected cat is strongly associated with the development of erythroid hypoplasia and consequent severe anemia. Infection rates are highest in catteries and multicat households, especially when cats have access to the outdoors. In the USA, 1-2% of healthy stray urban cats are persistently viremic. Not surprisingly, much higher percentages of sick, “at risk” cats are found to be infected. Persistently infected, healthy cats are the major reservoir of FeLV. Carriers excrete large quantities of virus in saliva. Lesser amounts of virus are excreted in tears, urine, and feces. Oronasal contact with infectious saliva or urine is the most likely mode of transmission. Nose-to-nose contact, mutual grooming, and shared litter trays and food dishes facilitate transmission. Bite wounds from infected cats are an efficient mode of transmission but occur relatively infrequently in cats kept indoors 100% of the time. Bites may be a more important mode of transmission in indoor-outdoor cats. Age resistance is significant. Because FeLV is a fragile, enveloped virus and because of age resistance, horizontal transmission between adults usually requires prolonged, intimate contact. Pathogenesis: After oronasal inoculation, the virus first replicates in oropharyngeal lymphoid tissue. From there, virus is carried in blood mononuclear cells to spleen, lymph nodes, epithelial cells of the intestine and bladder, salivary glands, and bone marrow. Virus later appears in secretions and excretions of these tissues and in peripheral blood leukocytes and platelets. Viremia is usually evident 2-4 wk after infection. The acute stage of FeLV infection (2-6 wk after infection) is rarely detected. It is typically characterized by mild fever, malaise, lymphadenopathy, and blood cytopenias. In ≥70% of adult cats, viremia and virus shedding are transient, lasting only 1-16 wk. A few cats continue to shed virus in secretions for several weeks to months after they cease to be viremic. Virus may persist in bone marrow for a longer period, but even this latent, or sequestered, infection usually disappears within 6 mo. Some FeLV-exposed cats (≤30%) fail to mount an adequate immune response and go on to become persistently (ie, permanently) viremic. Persistently viremic cats develop fatal diseases after a variable time period. In a group of persistently FeLV-positive cats, 50% die within ~1 yr; 83% of infected healthy cats die within 3½ yr of detection of their infection. Disorders Caused by FeLV: FeLV-related disorders are numerous and include immunosuppression, neoplasia, anemia, immune-mediated diseases, reproductive problems, and enteritis. The immunosuppression caused by FeLV is similar to that caused by feline immunodeficiency virus. There is an increased susceptibility to bacterial, fungal, protozoal, and other viral infections. The incidence of feline infectious peritonitis is increased in FeLV-infected cat colonies. Numbers of neutrophils and lymphocytes in the peripheral blood of affected cats may be reduced, and those cells that are present may be dysfunctional. Many FeLV-positive cats have low blood concentrations of complement; this contributes to FeLV-associated immunodeficiency and oncogenicity because complement is vital for some forms of antibody-mediated tumor cell lysis. Infusion of complement-rich serum can cause lymphoma regression in some cats. Much of the immunodeficiency caused by FeLV is thought to be due to the high degree of viral antigenemia. Lymphoid or myeloid tumors (eg, lymphoma, lymphoid leukemia, erythremic myelosis) develop in up to 30% of cats persistently infected with FeLV. FeLV-negative (ie, nonviremic) cats can also develop these tumors. Lymphoma is the most frequently diagnosed malignancy of cats. Most American cats with mediastinal, multicentric, or spinal forms of lymphoma are FeLV-positive. Renal and GI forms of lymphoma are more likely to be found in FeLV-negative cats. The anemia caused by FeLV is usually nonregenerative and normochromic. There is frequently an idiosyncratic macrocytosis. About 10% of FeLV-related anemias are hemolytic and regenerative. This form of anemia may be associated with hemobartonellosis or immune-mediated hemolysis, or both. Immune complexes formed in the presence of moderate antigen excess can cause systemic vasculitis, glomerulonephritis, polyarthritis, and a variety of other immune disorders. In FeLV-infected cats, immune complexes form

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under conditions of antigen excess, because FeLV antigens are abundant and anti-FeLV IgG antibodies are sparse. These conditions are ideal for the development of immune-mediated disease. Reproductive problems are common; 68-73% of infertile queens have been reported to be FeLV-positive, and 60% of queens that abort are FeLV-positive (although abortion is a relatively uncommon cause of feline infertility). Fetal death, resorption, and placental involution may occur in the middle trimester of pregnancy, presumably as a result of in utero infection of fetuses by virus transported across the placenta in maternal leukocytes. Occasionally, infected queens give birth to live, viremic kittens. Some of these may carry their infection into later life. Latently infected (ie, nonviremic) queens may pass virus on to their kittens in milk. Enteritis may develop, and it resembles feline panleukopenia both clinically and histopathologically. Clinical signs include anorexia, depression, vomiting, and diarrhea (which may be bloody). Because of the concurrent immunosuppression associated with FeLV infection, septicemia may develop. Recent evidence suggests that FeLV and feline panleukopenia virus may act synergistically to produce this syndrome. Other disorders may also develop. FeLV occasionally causes a neuropathy leading to anisocoria and hindlimb paralysis. Certain FeLV-induced lymphomas can produce identical clinical signs. If antineoplastic therapy is planned, it is important to distinguish neoplasia from neuropathy. Diagnosis: The ELISA test detects antigenemia rather than viremia. All ELISA-positive cats should have an indirect immunofluorescence assay (IFA) test done to confirm their status. The vast majority of IFA-positive cats are persistently viremic and have a poor long-term prognosis. Diagnosis of FeLV-induced neoplasia is similar to that of other tumors. Bone marrow examination may reveal leukemic involvement, even when the peripheral blood appears normal. Biopsy and histopathologic examination of abnormal tissues is often necessary for diagnostic confirmation. Treatment: Ideally, an FeLV-infected cat would be identified early and treated to eradicate its retroviral infection before FeLVrelated diseases had time to develop. Unfortunately, eradication of retroviral infections at any stage of disease is extremely difficult. Most infected cats are persistently viremic by the time their infection is diagnosed. Antiviral drugs based on nucleoside analogs have, in general, been of little benefit in the management of FeLV-infected cats. Although AZT (3'-azido-3'-deoxythymidine), at 20 mg/kg, PO, t.i.d., can prevent the development of persistent viremia if given shortly after viral inoculation, it is of little benefit when given to persistently viremic cats. Unfortunately, both AZT and PMEA (9-[2-phosphonylmethoxyethyl]adenine) cause adverse hematologic effects. FeLV-induced lymphoid malignancies can be treated using combinations of antineoplastic drugs; most protocols include prednisone, vincristine, and cyclophosphamide. Many FeLV-positive cats remain completely healthy for years. Prevention and Control: FeLV vaccines are intended to protect cats against FeLV infection or, at least, to prevent persistent viremia. Types of vaccines include killed whole virus, subunit, and genetically engineered. The following guidelines for vaccine use have been recommended: 1) Only healthy, febrile cats should be vaccinated. 2) Cats from a high-risk or unknown background should be tested for FeLV before vaccination. 3) All cats at risk of exposure to FeLV should be vaccinated. 4) FeLVpositive and FeLV-negative cats should be kept separated, even if the FeLV-negative cats have been vaccinated. 5) Although it may be preferable to use the same brand of vaccine for primary inoculations and boosters, use of a different brand for booster vaccinations should still produce an anamnestic response. This is because gp70 (SU) is the immunogen in all currently available vaccines. 6) Vaccines that prevent infection entirely are preferable to those that just prevent persistent viremia. 7) The brand of vaccine should be selected on the basis of clear research data. The preventable fraction should be mentioned in the vaccine manufacturers' product information. Feline Panleukopenia: Introduction (Feline infectious enteritis, Feline distemper) Feline panleukopenia is a highly contagious, often fatal, viral disease of cats; it is most severe in kittens. Nowadays, the disease is seen relatively uncommonly by veterinarians, presumably as a consequence of the widespread use of effective vaccines. However, infection rates remain high in feral, unvaccinated feline populations. Etiology, Transmission, and Pathogenesis: The causative parvovirus (feline panleukopenia virus [FPV]) infects and destroys actively dividing cells of all Felids and some members of related families (raccoon, mink, coatimundi, and kinkajou). Antigenically, FPV is indistinguishable from mink enteritis virus and is closely related to canine parvovirus type 2. Rapidly dividing cells in bone marrow, lymphoid tissues, intestinal epithelium, and in very young animals, cerebellum and retina are most affected. In pregnant queens, the virus may spread transplacentally to infect rapidly dividing embryonic or fetal cells, which leads to embryonic death, mummification, abortion, and stillbirth. Alternatively, infection of kittens in the perinatal period may destroy the germinal epithelium of the cerebellum, which leads to cerebellar hypoplasia, incoordination, and tremor. Feline cerebellar

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ataxia has become a relatively rare diagnosis, because most queens provide protective passive immunity to their kittens during the period of susceptibility. Virus particles are abundant in all secretions and excretions during the acute phase of illness and may be shed in the feces of survivors for up to 6 wk after recovery. The virus is extremely resistant to inactivation; it may survive ≥1 yr in a suitable environment and can be transported via fomites (eg, shoes, clothing, food bowls). However, it can be destroyed by a 6% solution of bleach (aqueous sodium hypochlorite). Cats are infected via the oronasal route by exposure to infected animals or their secretions or to fomites. Clinical Findings: Most infections are subclinical, as evidenced by the high seroprevalence of anti-FPV antibodies among unvaccinated, healthy cats. Those cats that do manifest signs of illness are usually <1 yr old. Typically, fever (104-107°F), depression, and anorexia develop after an incubation period of 2-7 days. Vomiting may develop 1-2 days after the onset of fever; it is usually bilious and unrelated to eating. Diarrhea tends to begin a little later. Extreme dehydration develops rapidly, even in the face of continued drinking. Physical examination reveals severe depression, dehydration, and sometimes abdominal pain. Abdominal palpation may induce vomiting. Thickened, turgid intestinal loops and mesenteric lymphadenopathy may be palpable. The duration of illness seldom exceeds 5-7 days. Indeed, young kittens with peracute panleukopenia often die within 24 hr of the onset of observed clinical signs. Mortality is high, especially in young kittens; losses of 25-90% are typical. Lesions: There may be few gross lesions in peracute cases, although typically, dehydration and emaciation are marked. The earliest changes are edema and necrosis of the thymus and mesenteric lymph nodes. The bone marrow may appear semifluid and fatty. The bowel walls are usually thickened and turgid; excessive gas may be present in some bowel loops. The serosal surfaces of severely affected bowel loops may be hyperemic, with ecchymotic or petechial hemorrhages. The liver, kidneys, and spleen may appear slightly swollen. Degeneration of hepatocytes and renal tubular epithelial cells is seen. Diagnosis: Neutropenia is a more consistent feature of FPV infection than is lymphopenia. Lymphopenia is most likely to be seen during the period of viremia (2-7 days after infection). Total WBC counts of ≤2000 cells/µL are associated with a poor prognosis. During recovery from infection, there is typically a rebound neutrophilia with a marked left shift. Diagnosis can be confirmed by showing the presence of FPV antigen in feces. The CITE® canine parvovirus test kit appears to detect FPV antigen during the acute phase of infection. Differential diagnoses include other causes of profound depression, panleukopenia, and GI signs. Salmonellosis, feline leukemia virus (FeLV), and feline immunodeficiency virus infections should be considered. There is recent evidence to suggest that the panleukopenia-like syndrome previously associated with FeLV infection is in fact caused by concurrent FeLV and FPV infections. Treatment and Prevention: Successful treatment of acute cases requires careful monitoring, vigorous fluid therapy, and supportive care. Electrolyte disturbances, acidosis, hypoglycemia, hypoproteinemia, anemia, and systemic infections commonly develop in severely ill cats infected with FPV, appropriate treatment should be administered. In addition to vigorous crystalloid infusion, transfusion of plasma or whole blood from an immune cat will help support plasma oncotic pressure, as well as provide some passive immunity. Parenteral, broad-spectrum antibiotic therapy is appropriate; however, nephrotoxic drugs (eg, gentamicin, amikacin) should be avoided or used with great care in dehydrated cats. Antiemetic therapy (eg, metoclopramide) may provide some relief and allow earlier enteral feeding. Parenteral nutrition may be beneficial in some cases. Excellent inactivated and modified live vaccines are available for prevention of FPV infection. Live vaccines should not be given to cats that are pregnant, immunosuppressed, or sick, or to kittens <4 wk old. Infectious Canine Hepatitis: Introduction Infectious canine hepatitis (ICH) is a worldwide, contagious disease of dogs with signs that vary from a slight fever and congestion of the mucous membranes to severe depression, marked leukopenia, and prolonged bleeding time. It also occurs in foxes, wolves, coyotes, and bears; other carnivores may become infected without developing clinical illness. Etiology and Pathogenesis: ICH is caused by a nonenveloped DNA virus, canine adenovirus 1 (CAV-1), which is antigenically related only to CAV-2 (one of the causes of infectious canine tracheobronchitis, Infectious Tracheobronchitis of Dogs). CAV-1 is resistant to lipid solvents and survives outside the host for weeks or months, but a 1-3% solution of sodium hypochlorite (household bleach) is an effective disinfectant. Ingestion of urine, feces, or saliva of infected dogs is the main route of infection. Recovered dogs shed virus in their urine for ≥6 mo. Initial infection occurs in the tonsillar crypts and Peyer's patches, followed by viremia and infection of endothelial cells in many tissues. Liver, kidneys, spleen, and lungs are the main target organs. Chronic kidney lesions and corneal clouding (“blue eye”) result from immune-complex reactions after recovery from acute or subclinical disease.
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Clinical Findings: Signs vary from a slight fever to death. The mortality rate is highest in very young dogs. The incubation period is 4-9 days. The first sign is a fever of >104°F (40°C), which lasts 1-6 days and is usually biphasic. If the fever is of short duration, leukopenia may be the only other sign, but if it persists for >1 day, acute illness develops. Tachycardia out of proportion to the fever may occur. On the day after the initial temperature rise, leukopenia develops and persists throughout the febrile period. The degree of leukopenia varies and seems to be correlated with the severity of illness. Signs are apathy, anorexia, thirst, conjunctivitis, serous discharge from the eyes and nose, and occasionally abdominal pain and vomiting. Intense hyperemia or petechiae of the oral mucosa, as well as enlarged tonsils, may be seen. There may be subcutaneous edema of the head, neck, and trunk. Clotting time is directly correlated with the severity of illness. It may be difficult to control hemorrhage, which is manifest by bleeding around deciduous teeth and by spontaneous hematomas, because of underlying disseminated intravascular coagulation. Respiratory signs usually are not seen in dogs with ICH; however, CAV-1 has been recovered from dogs with signs of infectious tracheobronchitis and from dogs with respiratory signs induced by exposure to the nebulated isolate. On recovery, dogs eat well but regain weight slowly. Seven to 10 days after the acute signs disappear, ~25% of recovered dogs develop bilateral corneal opacity, which usually disappears spontaneously. In mild cases of ICH, transient corneal opacity may be the only sign of disease. Chronic hepatitis may develop in dogs having low levels of passive antibody when exposed. Lesions: Endothelial damage results in “paintbrush” hemorrhages on the gastric serosa, lymph nodes, thymus, pancreas, and subcutaneous tissues. Hepatic cell necrosis produces a variegated color change in the liver, which may be normal in size or swollen. The gallbladder wall may be edematous and thickened; edema of the thymus may be found. Grayish white foci may be seen in the kidney cortex. Diagnosis: Usually, the abrupt onset and bleeding suggest ICH. Clinical evidence is not always sufficient to differentiate ICH from distemper ( Canine Distemper: Introduction), although the gross changes in the liver and gallbladder are more conclusive. Treatment: Blood transfusions may be necessary in severely ill dogs. In addition, 5% dextrose in isotonic saline should be given, preferably IV. In dogs with prolonged clotting time, SC administration of fluids may be dangerous. A broad-spectrum antibiotic should be given. Because tetracyclines may cause discoloration of the teeth during tooth development, they should not be used in puppies before their permanent teeth erupt. Although the transient corneal opacity (which may occur during the course of ICH or be associated with vaccination with attenuated CAV-1 vaccines) usually requires no treatment, atropine ophthalmic ointment may alleviate the painful ciliary spasm that is sometimes associated with it. The dog should be protected against bright light if corneal clouding occurs. Systemic corticosteroids are generally contraindicated for treatment of corneal opacity associated with ICH. Prevention: Modified live virus vaccines are available and are often combined with other vaccines. Vaccination against ICH is recommended at the time of canine distemper vaccinations. Annual revaccination against ICH is often practiced. Canine Ehrlichiosis The classical disease is an acute to chronic disease that is caused by infection of mononuclear cells by Ehrlichia canis and is transmitted by the brown dog tick, Rhipicephalus sanguineus . Ehrlichia platys is the cause of infectious cyclic thrombocytopenia and infects only platelets; it results in minimal if any hemorrhagic tendencies in dogs. The discussion below primarily describes infection in dogs caused by E canis . Etiology: The causative agent is seen rarely, appearing as colonies of coccoid bodies in the cytoplasm of usually monocytes. The brown dog tick ( Rhipicephalus sanguineus ) is the primary vector and reservoir and may transmit the disease for up to 5 mo after engorgement. Blood transfusions, or other means by which infected WBC are transferred, also transmit the disease. Clinical Findings: Signs arise from the involvement of the hemic and lymphoreticular systems and commonly progress from acute to chronic, depending on the strain of organism and immune status of the host. In acute cases, there is reticuloendothelial hyperplasia, fever, generalized lymphadenopathy, splenomegaly, and thrombocytopenia. Variable signs of anorexia, depression, loss of stamina, stiffness and reluctance to walk, edema of the limbs or scrotum, and coughing or dyspnea may occur. Most acute cases occur in the warmer months, coincident with the greatest activity of the tick vector. In the acute phases, the hemogram is usually normal but may reflect a mild normocytic, normochromic anemia; leukopenia; or mild leukocytosis. Thrombocytopenia is common, but petechiae may not be evident, and platelets may not be obviously decreased on a blood smear. Vasculitis and immune-mediated mechanisms induce a thrombocytopenia and hemorrhagic tendencies. Lymph node aspiration reveals hyperplasia.
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In the acute stage, death is rare; spontaneous recovery may occur, the dog may remain asymptomatic, or chronic disease may ensue. In chronic cases, the bone marrow becomes hypoplastic (a unique feature of E canis infection), and lymphocytes and plasmacytes infiltrate various organs. Depending on which organs are affected, and to what degree, signs are variable and appear without regard to season. Clinical findings may include marked splenomegaly, glomerulonephritis, renal failure, interstitial pneumonitis, anterior uveitis, and meningitis with associated cerebellar ataxia, depression, paresis, and hyperesthesia. Severe weight loss is a prominent finding. The hemogram is usually markedly abnormal in the chronic state. Frequently, severe thrombocytopenia may cause hemorrhagic diathesis. In dolichocephalic breeds, epistaxis is common. Hematuria, melena, and petechiae and ecchymoses of the skin and mucous membranes occur in all breeds. Variably severe pancytopenia (mature leukopenia, nonregenerative anemia, thrombocytopenia, or any combination thereof) may occur. Aspiration cytology reveals reactive lymph nodes and, usually, marked plasmacytosis. Frequently, polyclonal, or occasionally monoclonal, hypergammaglobulinemia occurs. Lesions: During the acute stage, lesions generally are nonspecific, but splenomegaly and heavy, discolored lungs are common. Histologically, there is lymphoreticular hyperplasia, and lymphocytic and plasmacytic perivascular cuffing. In chronic cases, these lesions may be accompanied by widespread hemorrhage and increased mononuclear cell infiltration of organs. Diagnosis: Because thrombocytopenia is a relatively consistent finding, a platelet count is an important screening test. Clinical diagnosis is confirmed by demonstrating the organisms within WBC, although this can be fortuitous. Low numbers of organisms make demonstration difficult, except in the acute phase before treatment. More commonly, a diagnosis is made by a combination of clinical signs, positive indirect serum fluorescent antibody (FA) titer, and response to treatment. The antibody response may be delayed up to 28 days; thus, serologic testing may not be a reliable diagnostic tool early in the course of the disease. During the acute stage, differential diagnoses include other causes of fever and lymphadenomegaly (eg, Rocky Mountain spotted fever, brucellosis, blastomycosis, endocarditis); immune-mediated diseases, especially thrombocytopenia and systemic lupus erythematosus; and lymphosarcoma. During the chronic stage, differential diagnoses include estrogen toxicity, myelophthisis, immune-mediated pancytopenia, and other multisystemic diseases associated with specific organ dysfunction (eg, glomerulonephritis). Treatment: The drug of choice for all forms of ehrlichiosis is tetracycline. Because of better intracellular penetration, doxycycline (5-10 mg/kg, PO or IV, daily for 10-14 days) is effective in some cases in which tetracycline fails. Two doses of imidocarb dipropionate (5-7 mg/kg, IM), 2 wk apart, are variably effective against both ehrlichiosis and babesiosis; however, the drug is not approved for use in the USA. In acute cases, the temperature returns to normal within 24-48 hr after treatment, and the dog becomes more active and begins to eat. In chronic cases, the hematologic abnormalities may persist for 3-6 mo, although clinical response occurs much sooner. Prevention: Prevention is enhanced by controlling ticks and using indirect FA-negative blood donors. Tetracycline (6.6 mg/kg, PO, daily) is an effective preventive in kennels in which ehrlichiosis is endemic. Rocky Mountain Spotted Fever (Tick fever) Rocky Mountain spotted fever (RMSF) is a disease of man, dogs, and other small mammals that is caused by Rickettsia rickettsii . Because Dermacentor andersoni and D variabilis transmit the disease, >80% of the cases occur in dogs that frequent the outdoors. Because of their susceptibility, dogs are an excellent sentinel of R rickettsii . Direct transmission from dogs to man has not been reported. Clinical Findings: Early signs may include any combination of fever (up to 105°F [40.5°C]), anorexia, lymphadenopathy, polyarthritis, coughing or dyspnea, abdominal pain, and edema of the face or extremities. Petechiation occurs in the most severe cases, if at all, and is generally confined to the mucous membranes. Neurologic manifestations are common and may include altered mental states, vestibular dysfunction, and paraspinal hyperesthesia. Focal retinal hemorrhage is a consistent finding during the early course of disease. Thrombocytopenia is common but generally mild enough to be overlooked on a peripheral blood smear. Leukopenia occurs during the early stages of infection and in untreated cases is followed by progressive leukocytosis. Generally, serum biochemical abnormalities are mild but may include hypoproteinemia, hypoalbuminemia, azotemia, hyponatremia, hypocalcemia, and increased liver enzyme activities. Lesions: Vascular endothelial damage is due to direct cytopathic effects of the rickettsiae. Severity of the necrotizing vasculitis can be directly correlated to the infective dose. Vascular endothelial damage and thrombocytopenia contribute to development of petechiae and ecchymoses. Necrosis of the extremities (acryl gangrene) or disseminated intravascular coagulation can develop in severely affected dogs.
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Diagnosis: Indirect FA titer is the most sensitive test. Differential diagnoses include other causes of fever of unknown origin. The therapeutic response is generally dramatic, as it is in other canine rickettsial diseases. Immunity appears to be lifelong after natural infection; therefore, recurrent episodes of tick fever should not be attributed to RMSF. Treatment: The tetracyclines at 22 mg/kg, PO, t.i.d. for 2 wk, are effective. Supportive care for dehydration and hemorrhagic diathesis may be necessary. Due to alterations in vascular integrity, conservative rates of fluid administration are advised. Precautions should be taken for the safe removal and control of ticks.

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Immune System Immunopathologic Mechanisms: Introduction Immunopathologic mechanisms are called immune-mediated diseases. There are four general classical classifications of these diseases, which are mediated either through antibodies (Types I, II, and III) or by cells (Type IV). A subpopulation of lymphocytes derived from the thymus gland (T cells) and soluble products produced from these cells (cytokines) are responsible for coordinating and regulating the specific immune response. The T cells that are responsible for this regulatory function are also called T-helper cells. T-helper cells can be further classified based on their expression of different cytokines and are called TH1 or TH2 cells. Both normal and immunopathologic immune responses are regulated at least in part by these two subpopulations of T-helper cells. Lymphocytes in the TH2 subpopulation are responsible for producing, among other things, the cytokines IL4, IL5, and IL10. These cells and cytokines drive the immune system toward an IgE-mediated (allergic, anaphylactic) response. In contrast, the lymphocytes in the TH1 subpopulation and its cytokines IL2 and gamma interferon drive the immune system toward an IgG-mediated response. Also, these cells and cytokines may play a critical role in the induction of T-cytotoxic lymphocytes. Therefore, attempts to regulate the immune system should focus primarily on the regulation of these subpopulations of lymphocytes and the cytokines they produce. Type I Reactions (Anaphylaxis) Anaphylaxis is an acute systemic manifestation of the interaction of an antigen (allergen) binding to IgE antibodies, which are bound to mast cells and basophils. This binding of antigens to cell-bound IgE antibodies triggers the release of chemical substances from the mast cells and basophils. The major biologically active mediators produced by mast cells and basophils include histamine, leukotrienes, the eosinophilic chemotactic factor, platelet activating factor, kinins, serotonins, and proteolytic enzymes. These chemicals directly affect both the vascular system, causing vasodilation and increased vascular permeability, and smooth muscles, causing contraction. Additionally, they result in the migration of eosinophils to the triggering site. The severity of the reaction depends on the type of antigen, the amount of IgE antibodies the animal has produced, and the amount of antigen and route of exposure. Agents that can cause anaphylactic and allergic reactions are numerous and include the venom of stinging and biting insects, vaccines, drugs of any kind, food substances, and blood products. Clinical signs can be localized or generalized and include restlessness and excitement, itch around the head or site of exposure, facial edema, salivation, lacrimation, vomiting, abdominal pain, diarrhea, dyspnea, cyanosis, shock, incoordination, collapse, convulsions, and death. Dogs differ from other domestic animals in that the major organ affected by shock is the liver, rather than the lung. Signs in dogs are associated with the constriction of hepatic veins, which results in portal hypertension and visceral pooling of blood. Therefore, GI signs rather than respiratory signs are more apt to be seen in dogs. Supportive therapy, in addition to treating respiratory distress, consists of the administration of epinephrine (both locally and systemically as needed), IV fluids for the treatment of shock, antihistamines (systemically for severe acute anaphylaxis or orally as a means to control chronic signs of allergy or more mild allergic signs), and corticosteroids if needed. Type II Reactions (Antibody-mediated cytotoxic reactions) Type II reactions occur when an antibody binds to an antigen present on the surface of the cell. This antibody-antigen complex then can activate the complement pathway and result in cell lysis or, through an antibody-mediated or complement-fragment-mediated receptor binding of a phagocytic cell, an antibody-mediated cytotoxicity reaction can ensue. It is unclear what triggers this antibody-mediated cytotoxicity but, as with all immune-mediated pathologic events, the combination of external factors and an infectious process in a genetically predisposed animal can lead to the development of immunopathologic disorders. It has been hypothesized that acute viral infections can lead to changes in the immune regulatory pathways that result in an overreaction of the immune system or to a change in the protective immune response to one that results in a pathologic process. Also, cross-reactive antibodies can develop during an infectious process. These cross-reactive antibodies directed toward an infectious agent will bind to normal tissue and result in antibody-mediated cytotoxicity. For example, in streptococcal infection in horses, in which a cross-reaction between streptococcal antigen and vascular basement membranes can occur, an immunopathologic disease can result. Lastly, certain pathogens such as Babesia or Haemobartonella may parasitize tissues such that the immune response will destroy those tissues as part of the protective mechanism. Clinical signs of a Type II hypersensitivity are variable and depend on the organ in which the reaction is occurring. They can include fever, cutaneous manifestation, polyarthritis, pain or joint swelling, and CNS signs. Glomerular nephritis is recognized by proteinuria or acute renal failure. Hematologic abnormalities, such as hemolytic anemia, thrombocytopenia, neutropenia, or lymphopenia, may be seen. Vague signs such as vomiting, diarrhea, or abdominal pain may also be seen. The diagnosis is primarily made by elimination of more obvious causes for the signs mentioned above and by histopathologic and immunohistopathologic analysis of a biopsy of a particular organ. Supportive treatment consists of elimination of the offending infectious agent (if determined) and anti-inflammatory or immunosuppressive drug therapy.
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Type III Reactions (Immune complex disease) Type III reactions occur when antigen-antibody complexes are deposited along the endothelium. These complexes stimulate, both directly and via the complement pathway, a neutrophilic inflammatory response and vascular damage. The result is a multisystemic vasculitis. The most commonly affected sites include the joints, skin, kidneys, lungs, and brain. The prerequisite for the development of such disease is continued presence of soluble antigen and continuous production of antibody. When there is slightly more antigen than antibody, the soluble complexes become deposited along endothelial cells. The reason for their deposition is not entirely clear; however, it is presumed that large complexes are removed by phagocytosis and very small complexes can easily pass through the cellular membrane, whereas complexes of intermediate size become trapped on the basement membrane of endothelial cells. These deposited immune complexes then activate the complement cascade. Complement fragments cleaved from precursor molecules in this cascade incite inflammatory cells and are also vasoactive directly. The end result is a vasculitis. There are a number of reasons for the continuous presence of antigen, including chronic persistent infectious processes (due to viruses, bacteria, fungi, protozoa, or parasites) and certain neoplastic conditions, particularly lymphoreticular neoplasms. Administration of drugs can result in an animal mounting an antibody response to the drug, and chronic antigen exposure is possible if the drug is continually administered or in the case of repository medications. Lastly, some animals respond to self antigens, which represent a source of chronic antigen. In many cases, the origin of the antigen cannot be determined and, therefore, the cause of the disease is unidentifiable. Clinical signs are variable but include fever, cutaneous manifestations (such as erythema multiforme), and a polyarthritis (demonstrated by the presence of a shifting-leg lameness or painful, swollen joints). Other signs include ataxia, change in behavior, proteinuria, isosthenuria, polydipsia, polyuria, or vague signs such as vomiting, diarrhea, or abdominal pain. Diagnosis is based on the elimination of more common causes of the clinical signs mentioned above. Supporting evidence to confirm the diagnosis includes establishing a temporal relationship if a drug is suspected as the cause, identifying chronic infectious processes or malignancies, and performing various laboratory tests (such as a Coombs' test or an antinuclear antibody test) as well as histopathology and immunohistochemistry analyses to identify immune-mediated vasculidites or nephritis. Type IV Reactions (Cell-mediated immune reactions) Cell-mediated immune reactions occur when T-helper cells respond to foreign antigen or small molecules bound to cell tissue to form a complete antigen. The T-cell elaborates a variety of cytokines, including interleukin-1. The elaboration of interleukin-1 and other cytokines attracts mononuclear phagocytes to the site of antigen. The infiltration of mononuclear cells and the elaboration of a variety of substances from these cells result in the pathologic processes involved in cellmediated immune reactions. The antigens usually responsible for the development of Type IV reactions include intercellular bacteria or parasites, some viruses, chemicals, and (in certain situations) cell antigen. This type of reaction can occur in any organ and, therefore, the clinical signs will vary depending on the organ affected. The diagnosis is based on ruling out other causes for organ-specific diseases and by a classic histologic description of delayed-type hypersensitivity reaction in tissue. The goals of treatment are to provide supportive therapy based on the organ-specific disease process, to identify (if possible) and eliminate the source of antigen that is responsible for the reaction, and to provide anti-inflammatory or immunosuppressive therapy if needed. Diseases Involving Anaphylactic Reactions: Overview (Type I reactions, Atopic disease) Type I reactions are either systemic or localized.

Allergic asthma is less common in other animals than in man. Among animals, it is most frequent in cats, in which the signs are similar to those in man. It occurs more frequently in summer and after going outdoors; individual attacks can be transient and mild, or protracted and severe (status asthmaticus). Mild attacks may manifest as wheezing and coughing; in severe attacks, there may be expiratory dyspnea, hyperinflation of the lungs, aerophagia, cyanosis, and frantic attempts to obtain air. Intestinal allergies (food allergies) are principally seen in dogs and cats, particularly kittens. Allergic gastritis is manifest by vomiting, which occurs 1 to >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
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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)
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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
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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
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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
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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
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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. The disease is usually more severe in goats than in sheep.
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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
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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 <50% being lethal. The areas within a home with the necessary humidity are limited, and suitable outdoor sites are even rarer. Flea development occurs outdoors only where the ground is shaded and moist and where the flea-infested pet spends a significant amount of time so that adult flea feces will be deposited into the larval environment. Likewise, in the indoor environment, flea larvae probably survive only in the protected microenvironment under a carpet or in cracks between hardwood floors in humid climates. After completing its development, the mature larva produces a silk-like cocoon in which it pupates. Once the pupa has fully developed (1-2 wk), the preemerged adult flea emerges from the cocoon when properly stimulated by physical pressure, carbon dioxide, substrate movement, or heat. The preemerged adult (which is a fully formed adult flea) residing in the cocoon is the stage that can extend the longevity of the flea. If the preemerged adult does not receive the proper stimulus to emerge, it can remain quiescent in the cocoon for several weeks until a suitable host
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arrives. Preemerged adult fleas can survive for up to 6 mo inside the cocoon if protected from desiccation. Newly emerging fleas move to the top of the carpet pile or vegetation, where they are more likely to encounter a passing host. If the newly emerged cat flea does not immediately acquire a host, it can survive several days before requiring a blood meal. It is the newly emerged unfed fleas that infest pets and bite people. Cat fleas that have found a preferred host (eg, dog, cat, opossum, etc) do not leave their host unless forced off by grooming activity or insecticides. Depending on temperature and humidity, the entire life cycle of the cat flea can be completed in as little as 12-14 days or can be prolonged for up to 6 mo. Fleas mate after feeding, and egg production begins within 24-48 hr of females taking their first blood meal. Female cat fleas can produce up to 40-50 eggs/day during peak egg production, averaging 27 eggs/day through 50 days, and may continue to produce eggs for >100 days. The cat flea is susceptible to cold. No stage of the life cycle (egg, larva, pupa, or adult) can survive exposure to <3°C (37.4°F) for several days. Therefore, cat fleas survive winters in north temperate climates as adults on untreated dogs and cats or on small wild mammals (eg, raccoons or opossums) in the urban environment. In heavy infestations, fleas can cause iron deficiency anemia, particularly in young animals. The cat flea is also involved in disease transmission. Cat fleas also serve as the intermediate host of the nonpathogenic subcutaneous filarid nematode of dogs, Dipetalonema reconditum . Dipylidium caninum , the common intestinal cestode of dogs and cats (and rarely children), develops as a cysticercoid in C felis , C canis , and P irritans . Flea larvae ingest the eggs of the tapeworm, which develop into cysticercoids in the body of the flea. When grooming themselves, dogs and cats may ingest infected fleas, and the cysticercoids are released. Flea allergy dermatitis (FAD) or flea bite hypersensitivity is the most common dermatologic disease of domestic dogs in the USA. Cats are also afflicted with FAD, which is one of the major causes of feline miliary dermatitis. FAD is most prevalent in the summer. Temperature extremes, low humidity, and high elevations (>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
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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
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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 <1 yr old,and 90% of these cases are thought to resolve spontaneously. Lesions consist of areas of focal alopecia and erythema. A percentage of these cases will progress to the generalized form. Generalized demodicosis is a severe disease with generalized alopecia, papules, pustules, and crusting. Lesions are usually aggravated by secondary bacterial infections, and pododermatitis is common. Dogs can have systemic illness with generalized lymphadenopathy, lethargy, and fever when deep pyoderma, furunculosis, and draining tracts are seen. Deep skin scrapings reveal mites, eggs, and larval forms in high numbers. Whenever generalized demodicosis is diagnosed in an adult dog, medical evaluation to identify an underlying systemic disease should be pursued. Localized demodicosis can be treated by topical application of rotenone ointment or amitraz. The prognosis for this form is usually good. The only approved treatment for generalized demodicosis is whole body amitraz dips (0.025%) applied every 2 wk; the entire hair coat should be clipped, and a benzoyl peroxide shampoo should be used for its follicular flushing activity before the dip is applied. The secondary bacterial infection must be treated with the appropriate antibiotic. Feline Demodicosis: Two species of mites cause disease in cats. Demodex cati is thought to be a normal inhabitant of feline skin. It is a follicular mite, similar to but narrower than the canine mite. The other species of Demodex remains unnamed; it is shorter,
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with a broad abdomen, and is found only in the stratum corneum. Feline demodicosis is uncommon. In localized demodicosis, there are one or several areas of focal alopecia on the head and neck. In generalized disease, alopecia, crusting, and secondary pyoderma of the whole body are seen. The generalized form has also been associated with other systemic disease, especially diabetes mellitus. In some cases, ceruminous otitis externa has been the only clinical sign. Pruritus is variable; both forms of the mite can cause similar disease, but cats infested with the unnamed mite are frequently pruritic. Diagnosis is made by skin scrapings, although mite numbers are often small. Medical evaluation is indicated in cats with generalized disease. Dermatophyte cultures are essential, because dermatophytosis and demodicosis can be concurrent conditions. Prognosis of generalized demodicosis can be unpredictable because of its potential relationship with systemic disease. Tumors Of The Skin And Soft Tissues: Introduction Cutaneous tumors are the most frequently diagnosed neoplastic disorders in domestic animals, in part because they can be identified easily and in part because the constant exposure of the skin to the external environment predisposes this organ to neoplastic transformation. Chemical carcinogens, ionizing radiation, and viruses all have been implicated, but hormonal and genetic factors may also play a role in development of cutaneous neoplasms. Because cutaneous tumors are so diverse, their classification is difficult and often controversial. To avoid confusion, the following terms are used in this discussion: A hamartoma (nevus) is a localized developmental defect associated with enlargement of one or more elements of the skin. A sebaceous hamartoma, for example, refers to a localized region of the skin where sebaceous glands are extremely prominent and sometimes malformed. Although by strict definition, hamartomas are present at birth, they may occasionally take a long time to reach a size when they are clinically apparent and may not be diagnosed until an animal is mature. A benign neoplasm is localized, noninfiltrative, and because it is surrounded by a capsule, easily excisable. A neoplasm of intermediate malignancy is locally infiltrative and difficult to excise but does not metastasize. A malignant neoplasm is infiltrative with metastatic potential. Although cutaneous neoplasms characteristically are nodular or papular, they also can occur as localized or generalized alopecic plaques, erythematous and pigmented patches and plaques, wheals, or nonhealing ulcers. Therapy depends largely on the type of tumor, its location and size, and signalment of the animal. For benign neoplasms associated with neither ulceration nor clinical dysfunction, no therapy may be the most prudent option, especially in aged dogs. For more aggressive neoplastic diseases or benign tumors that inhibit normal function or are cosmetically unpleasant, there are several therapeutic options. For most, surgical intervention with complete excision provides the best chance of a cure at least cost and often with the fewest side effects. Lumpectomy is adequate for benign lesions, but if a malignancy is suspected, the lesion should be removed with wide (3 cm) surgical margins. For tumors that cannot be completely excised, partial removal or debulking may prolong the life of the animal and increase the effectiveness of radiation or chemotherapy. Cryosurgery is also an option, although it is more effective for benign, superficial lesions than for malignant cutaneous neoplasms. Radiation therapy is of most value for infiltrative neoplasms that are not surgically resectable, or when surgical intervention would cause unacceptable physical impairment. Chemotherapy can be used either as a primary method for treatment of malignant neoplasms or as an adjunct to surgical or radiotherapy. Other forms of therapy include hyperthermia, laser therapy, and photodynamic therapy. Squamous Cell Carcinomas (Epidermoid carcinomas, Prickle cell carcinomas) Thought to arise from either the epidermis or the epithelium of the superficial (infundibular) regions of the outer root sheath of the hair follicle, squamous cell carcinomas have been recognized in all domestic animals. Although most arise without antecedent cause, in many species, prolonged exposure to sunlight is a major predisposing factor. In addition, a unique form of feline squamous cell carcinoma associated with papilloma virus infection has recently been described. In dogs, these are the most frequently diagnosed carcinomas arising in the skin. Two forms are recognized— cutaneous and subungual. Cutaneous squamous cell carcinomas are tumors of older dogs, with Bloodhounds, Basset Hounds, and Standard Poodles the breeds at greatest risk. Lesions commonly arise on the head, distal extremities, ventral abdomen, and perineum. The etiology of most of these tumors is undefined; however, some are induced by prolonged solar injury. They develop in a ventral location because the poorly haired skin offers minimal shielding from ultraviolet radiation, many animals sun themselves lying on their backs, and perhaps solar radiation may reflect from the ground upward. Before a carcinoma develops, animals acquire focal zones of lichenification, hyperkeratosis, and erythema known as solar keratosis (solar dermatosis, actinic keratosis, senile keratosis). Subungual squamous cell carcinomas are most commonly found in Giant and Standard Schnauzers, Gordon Setters, Briards, Kerry Blue Terriers, and Standard Poodles. Generally, all are dark-coated breeds, and a dark coat color has been associated with the development of subungual cell carcinomas arising on multiple digits, often on different extremities. In cats, cutaneous squamous cell carcinomas most commonly develop in conjunction with chronic solar injury. Consequently, they usually develop on the pinnae, frontal ridges, or eyelids of cats that have white skin in these regions.

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There is no breed or sex predilection. As in dogs, solar keratosis often precedes development of a malignant tumor. Those not caused by sun exposure most commonly develop on the digits, but subungual forms are uncommon. Cutaneous squamous cell carcinomas are the most common malignant neoplasm in horses. They generally develop in adult or aged horses with white or part-white coats; breeds at risk include Appaloosa, Belgian, American Paint, and Pinto. Although they can arise anywhere on the body, these tumors most commonly arise in nonpigmented, poorly haired areas near mucous membranes. Thus, the periorbital regions, lips, nose, and anus and external genitalia (especially the penile sheath) are sites most likely to undergo malignant transformation. In cattle, these tumors are most common in breeds with white hair and poorly pigmented skin (especially Holsteins and Ayrshires) and, as in horses, develop around the mucous membranes, usually at the mucocutaneous junctions. Solar keratoses often precede development of an invasive tumor; genetic factors, immunodeficiency, and viruses also have been suggested as playing a role. In sheep, squamous cell carcinomas are of economic significance in some parts of the world. The Merino breed is most at risk, and females more so than males. Tumors at all these sites develop in conjunction with solar injury, which is heightened when animals ingest photosensitizing plants. Squamous cell carcinomas are extremely uncommon in swine. Most squamous cell carcinomas are solitary lesions; however, multiple tumors may develop in conjunction with solar injury. They appear as endophytic or exo-endophytic lesions, the former as raised, irregular dermal masses with an ulcerated surface, and the latter as raised, irregular dermal masses covered by a papillated epidermis. Subungual squamous cell carcinomas of dogs are first identified by lameness or malformation or loss of the claw of the affected digit. In cattle with involvement of the horn, the first sign is distorted growth. Squamous cell carcinomas are characteristically invasive into adjacent soft and bony tissues. Infrequently, in cattle, they regress spontaneously. In small animals, long-term survival and the likelihood of metastasis are correlated with histologic differentiation. Well-differentiated tumors are slowly progressive or remain localized; undifferentiated tumors are more likely to metastasize or recur within 20 wk of excision. In general, failure of treatment is due to lack of control of local disease rather than metastasis. For dogs and cats, surgical excision is the treatment of choice, and margins of at least 2 cm are recommended. Excision may be combined with radiation or chemotherapy. Feline squamous cell carcinomas are more radiosensitive than their canine counterparts. Still, the 1-yr survival rate is <10% for invasive neoplasms. Immunotherapy, with either an autogenous vaccine made from the tumor tissue suspended in Freund's adjuvant, or nonspecific immunomodulation using Corynebacterium parvum , has had some success in treating ocular or horn core squamous cell carcinomas in cattle. Soft-tissue Sarcomas This group of malignancies includes equine sarcoids, fibromatoses, fibrosarcomas, malignant fibrous histiocytomas, neurofibrosarcomas, leiomyosarcomas, rhabdomyosarcomas, and variants of liposarcomas, angiosarcomas, synovial cell sarcomas, mesotheliomas, and meningiomas. As a group, sarcomas are widely recognized, yet poorly characterized neoplasms. Consequently, it is widely accepted that the cell of origin of all soft-tissue sarcomas is a primitive mesenchymal cell that can differentiate in many different directions. This makes it difficult to define histopathologic criteria necessary for making an unequivocal diagnosis of specific spindle-cell sarcomas. Most spindle-cell sarcomas of domestic animals are locally infiltrative, difficult to excise, and yet seldom metastasize. Because, by definition, only malignant tumors have metastatic potential, these tumors should be considered benign; however, again by definition, benign neoplasms are not infiltrative, and those tumors should be considered malignant. In human pathology, infiltrative but nonmetastasizing mesenchymal spindle-cell tumors have been defined as “sarcomas of intermediate malignancy,” a concept used below. Clinically, four general principles relate to spindle-cell sarcomas and soft-tissue sarcomas: • The more superficial the location, the more likely the tumor is to be benign (deep tumors tend to be malignant). • The larger the tumor, the more likely it is to be malignant. • A rapidly growing tumor is more likely to be malignant than one that develops slowly. • Benign tumors are relatively avascular, whereas most malignancies are hypervascular. Excision is the treatment of choice; wide excision or amputation should be performed when anatomically feasible because spindle-cell sarcomas often infiltrate along fascial planes, making it difficult to determine from gross examination the peripheral margins of the tumor. The best, if not only, opportunity to completely remove a spindle-cell sarcoma is during the first surgical attempt; those that recur have a greater potential for metastasis, and the time between recurrence often shortens with each subsequent attempt at excision. In addition, many soft-tissue tumors have a “pseudocapsule,” which on gross examination gives the impression of complete encapsulation; these tumors should not be “shelled out” because neoplastic cells are usually present in the pericapsular connective tissues. Except for equine sarcoids, cryosurgery is usually not used for these tumors because some types, most notably fibrosarcomas, are resistant to freezing. Spindle-cell sarcomas generally do not respond well to conventional doses of radiation; however, higher doses have been reported to control ~50% of them for 1 yr. Surgical debulking followed by radiation is also an option for local control. Recently,
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chemotherapeutic protocols for sarcomas have become more accepted as a means of treatment. Most involve the use of adriamycin often in combination with other agents, including cyclophosphamide, vincristine, dacarbazine, and methotrexate. Although chemotherapy may improve the quality and prolong the of life of an affected animal, it is seldom curative. Equine sarcoids are the most frequently recognized neoplasm in horses. A viral etiology is suspected, and both papilloma virus and retrovirus particles have been identified on ultrastructural examination of sarcoids. In addition, cell-free extracts of bovine papilloma virus can induce a transient form of equine sarcoid when injected into horses. Evidence also suggests that sarcoids are transmissible by direct contact or via arthropod vectors or fomites, eg, contaminated brushes and needles. The most common site varies with geographic area; in the UK, the penis is the most commonly reported site, while in the northwest USA, the limbs are affected most frequently. Sarcoids are highly variable in appearance, and four manifestations are recognized: 1) verrucous, which may be confused with squamous papillomas or squamous cell carcinomas; 2) fibroblastic, which may be confused with granulation tissue or fibromas; 3) sessile or flat, which may be confused with flat warts (verruca plana); and 4) mixed verrucous and fibroblastic, which may be confused with fibropapillomas. They should be considered sarcomas of intermediate malignancy—they do not metastasize but are locally invasive. The fibroblastic and sessile forms are generally the most aggressive. Cryosurgery, after surgical debulking of larger lesions, is the treatment of choice. Radiation therapy using iridium may control up to 85% of equine sarcoids. Immunotherapy with inoculations of bacillus Calmette-Guérin (BCG) or cell wall extract of Mycobacterium bovis remains controversial; some reports indicate ~50% of tumors can be controlled with such immunomodulating therapies. Tumors so treated may take several months to regress. Treatment with flunixin meglumine and prednisolone 30 min before BCG inoculation is recommended. Lastly, BCG therapy should not be used when treated horses could be exposed to cattle because BCG can induce a positive tuberculin reaction in the latter. Fibromatosis (aggressive fibromatosis, extra-abdominal desmoids, desmoid tumors, low-grade fibrosarcomas, nodular fasciitis) is a sclerosing and infiltrative proliferation of well-differentiated fibroblasts derived from aponeuroses and tendon sheaths. They are generally seen on the heads of dogs, where they are commonly diagnosed as nodular fasciitis. Fibrosarcomas are aggressive mesenchymal tumors in which fibroblasts are the predominant cell type. They are the most common soft-tissue tumors in cats and are also common in dogs but are rare in other domestic animals. In dogs, these tumors are most common on the trunk and extremities. Gordon Setters, Irish Wolfhounds, Brittanies, Golden Retrievers, and Doberman Pinschers may be predisposed. Fibrosarcomas vary markedly in their appearance and size. Neoplasms arising in the dermis may appear nodular. Those arising in the subcutaneous fat or subjacent soft tissues may require palpation to identify. They appear as firm, fleshy lesions involving the dermis and subcutaneous fat and often invade musculature along fascial planes. When tumors are multiple, they are usually found within the same anatomic region. Fibrosarcomas with abundant interstitial proteoglycans (connective tissue mucins) are called myxosarcomas or myxofibrosarcomas. Myxosarcomas remain poorly defined in veterinary medicine, and many of them could be characterized as variants of liposarcomas or malignant fibrous histiocytomas. Fibrosarcomas in dogs are invasive tumors; ~10% metastasize. Factors that affect whether a fibrosarcoma can be completely excised include the rate of growth (as defined by the mitotic index and quantity of necrosis), the degree of cellular atypia, the infiltrative nature of the tumor, and its size and anatomic location. Three forms of fibrosarcoma are recognized in cats: a multicentric form in the young (generally <4 yr old) caused by the feline sarcoma virus (FSV); a solitary form in the young or old, in which FSV has not been implicated; and a fibrosarcoma that develops in the soft tissues where cats are commonly vaccinated. This latter neoplasm is being recognized with increasing frequency in the USA (see also Disease-management Interaction: Small Animals: Introduction ). Aluminum (commonly used in adjuvants) has been identified in vaccine-induced fibrosarcomas, and a prolonged proliferation of fibroblasts in response to the adjuvant may predispose them to undergo neoplastic transformation. Although commonly classified as “fibrosarcomas,” vaccination-site sarcomas are extremely heterogeneous and may be appropriately called malignant fibrous histiocytomas (giant cell tumors), liposarcomas, osteosarcomas, or chondrosarcomas. Surgical excision is the treatment of choice, but recurrence is common (>70% within 1 yr of the initial surgery). Vascular Tumors Hemangiomas of the skin and soft tissues are benign proliferations that closely resemble blood vessels. Whether these are neoplasms, hamartomas, or vascular malformations remains undefined, and no clear criteria exist that allow for their separation. They are most commonly identified in dogs, occasionally in cats and horses, and rarely in cattle and pigs; they are an exceptional finding in other domestic animals. In dogs, they are tumors of adult dogs and most commonly develop on the trunk and extremities. Cats most frequently develop hemangiomas when they are adults. Lesions are most common on the head, extremities, and abdomen. In horses, they are most common on the distal extremities of young (<1 yr old) animals. In cattle, they may be seen as congenital lesions or in older animals. Hemangiomas are single to multiple, circumscribed, often compressible, red to black nodules. The lining epidermis may be unaffected or ulcerated or papillated. Small, superficial hemangiomas that often appear as a “blood blister” are known as angiokeratomas. When erythrocytes are sparse or absent within vascular lumens, the term lymphangioma is applied. Hemangiomas are benign, but their tendency to
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ulcerate and grow to be quite large, along with the importance of confirming the diagnosis to make a prognosis, indicate removal. Excision is the treatment of choice; however, in large animals in which the lesions may be large and involve the distal extremities, this may be difficult. In these cases, cryosurgery or radiation therapy may be necessary. Hemangiopericytomas (canine spindle-cell sarcoma, canine malignant fibrous histiocytoma, canine neurofibrosarcoma, canine perineuroma) are common in dogs and rare in cats (if they occur at all). A tumor initially named because it was thought to be derived from fibroblastic cells that surround small vessels, the appropriateness of the term “hemangiopericytoma” remains a topic of debate. These tumors develop most commonly on the distal extremities and thorax of older dogs. They typically present as firm, multilobulated, solitary lesions with irregular borders, most commonly in the subcutaneous fat but sometimes in the dermis. Hemangiopericytomas are of intermediate malignancy and have limited metastatic potential. Complete excision is the treatment of choice but, due to their infiltrative nature, ~30% recur. Angiosarcomas, arguably the most aggressive of all soft-tissue tumors, are composed of cells that have many functional and morphologic features of normal endothelium. Although these tumors are often divided into hemangiosarcomas (of purported blood vessel origin) and lymphangiosarcomas (of lymphatic vessel origin), such a distinction is arbitrary. The term angioendothelioma is also used. Angiosarcomas of the skin and soft tissues are seen in all domestic animals but are most common in dogs, generally in adult or aged animals. They appear as one or more erythematous nodules present anywhere in the skin or underlying soft tissues. Less frequently, they appear as a poorly defined bruise. All grow rapidly, often are associated with large zones of necrosis and thrombosis, and typically are red to black on cut section. Tumors often diagnosed as lymphangiosarcomas may have much less lumenal blood, and the vascular spaces are typically filled with serum. Characteristically, angiosarcomas create their own vascular space by dissecting through soft tissues. Distant metastasis, especially to the lungs and liver, is common. In other domestic animals, these tumors do not appear to behave as aggressively, and postexcisional recurrence rather than metastasis is more common. For all species, wide excision is the treatment of choice. Recently, adjuvant chemotherapy consisting of vincristine, doxorubicin, and cyclophosphamide has been reported to shrink angiosarcomas; however, effects of this therapy on long-term survival remain to be defined. Cutaneous Mast Cell Tumors These tumors (also called mastocytomas, mast cell sarcomas) are the most frequently recognized malignant or potentially malignant neoplasms of dogs. In addition, leukemic and visceral forms can occur. These tumors may occur in dogs of any age (average 8-10 yr). They may occur anywhere on the body surface as well as in internal organs, but the limbs (especially the posterior upper thigh), ventral abdomen, and thorax are the most common sites; ~10% are multicentric. Many breeds appear to be predisposed, especially Boxers and Pugs (in which tumors are often multiple), Rhodesian Ridgebacks, and Boston Terriers. The tumors vary markedly in size, and clinical appearance alone cannot establish a diagnosis. Most commonly, they appear as raised, nodular masses that on palpation may be soft to solid. Although they often seem encapsulated, mast cell tumors in dogs are seldom discrete. Rather, they consist of a highly cellular center surrounded peripherally by a “halo” of smaller numbers of mast cells that palpate as normal skin. Dogs can also develop clinical signs associated with the release of vasoactive products from the malignant mast cells. Most common is gastroduodenal ulceration that may be present in up to 25% of cases. Cytologic evaluation of Wright's-stained, fine-needle aspirates or impression smears can be used to establish the diagnosis of mast cell tumors in dogs. Although there is believed to be a benign variant of canine mast cell tumor, there is no clinical or microscopical means of identifying it. In addition, small mast cell tumors may remain quiescent for long periods before becoming aggressive. Thus, all should be treated as at least potential malignancies. Treatment depends on the clinical stage of the disease. For Stage I tumors (a solitary tumor confined to the dermis without nodal involvement), the preferred treatment is complete excision with a wide margin; at least 3 cm of healthy tissue surrounding all palpable borders should be removed in an attempt to excise both the nodule and its surrounding “halo” of neoplastic cells. If histologic evaluation suggests that the tumor extends beyond the surgical margins, reexcision should be attempted. Alternatively, because mast cells are sensitive to radiation, radiation therapy may be curative if the remaining tumor is small or can only be seen microscopically. Combined radiation and hyperthermia may be more effective than radiation alone. At present, there is no agreed upon mode of therapy for Stage II-IV mast cell tumors. For Stage II tumors (a solitary tumor with regional lymph node involvement), options include excision of the mass and the affected regional node (if feasible), prednisolone, and radiotherapy, used either singly or in combination. Treatment of Stage III (multiple dermal tumors with or without lymph node involvement) or Stage IV (any tumor with distant metastasis or recurrence with metastasis) tumors is generally palliative. In cats, cutaneous mast cell tumors are common. In addition to cutaneous tumors, systemic, leukemic, and GI forms have been recognized. Two distinct variants of the form are recognized—a mast cell type analogous to, but not identical with, cutaneous mast cell tumors in dogs, and a histiocytic-type unique to cats.

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The tumors are single, alopecic nodules, generally 2-3 cm in diameter, that occasionally extend into the subcutaneous fat. Lymphoid nodules are common, eosinophils are rare. Unlike mast cell tumors in dogs, those in cats are benign, and generally, atypia and clinical behavior are poorly correlated. Surgical excision is the treatment of choice. Usually, the older the cat, the fewer the lesions. In horses, mast cell tumors are uncommon, benign tumors. Lesions may develop anywhere on the body but are most common on the head and legs. Typically, there is a single, solitary mass in the dermis or subcutaneous fat that may expand to involve the underlying musculature. The tumor begins as a nodule composed of a generally monomorphic proliferation of mast cells. As the lesion evolves, the mast cells are limited to aggregates in a fibrous stroma that surrounds large foci of liquefactive necrosis containing numerous eosinophils. In the late stages, the necrotic foci undergo dystrophic mineralization, and mast cells may be very difficult to identify. Once mineralization occurs, the lesion is gritty on sectioning. Alopecia and ulceration are variable features. Excision is the treatment of choice. These lesions do not metastasize. A variant of cutaneous mast cell tumor occurs in newborn foals, in which the lesions may become generalized but regress over time, suggesting an equine equivalent of urticaria pigmentosa in man. Eosinophilic Granuloma Complex: Introduction The etiology of this group of diseases that affects cats, dogs, and horses has focused on an underlying hypersensitivity reaction. This is particularly true in cats and horses. Eosinophilic Ulcer: This well-circumscribed, erythematous, ulcerative lesion, usually not painful or pruritic, is usually found on the upper lip. Although reported to occur, progression to squamous cell carcinoma is extremely rare. Histology shows an ulcerative dermatitis, with a cellular infiltrate of neutrophils, plasma cells, and mononuclear cells predominating. Mild to moderate fibroplasia is common. Tissue or peripheral eosinophilia is uncommon. Eosinophilic Plaque: This well-circumscribed, erythematous, raised lesion is most commonly found in the medial thigh region and abdominal regions; it is extremely pruritic. Regional lymphadenopathy can be seen. Histology shows a diffuse eosinophilic dermatitis, with marked inter- and intracellular edema and vesicles containing eosinophils in the epidermis and dermis. Mast cells can also be present. Peripheral eosinophilia is common. Eosinophilic Granuloma: These usually raised, well-circumscribed, yellowish to pink lesions may be found anywhere on the body but are most common on the head, face, bridge of the nose, pinnae, pads of the feet, perineal region, lips, chin, oral cavity, and caudal thighs. The caudal thigh location is usually distinctly linear; however, linear lesions have been seen on other body locations but more commonly are papular, nodular or diffusely swollen, and firm. Histologically, a granulomatous inflammatory response surrounds degenerative collagen. In dogs, the lesions reported as eosinophilic granulomas histologically resemble the eosinophilic granuloma of cats, with marked collagen degeneration surrounded by a granulomatous and eosinophilic infiltrate. These lesions may occur as ulcerated or vegetative masses in the oral cavity or, less commonly, as plaques, nodules, or papules on the lips and other areas of the body. Any breed may be affected, but Siberian Huskies may be at greater risk. In horses, the disease has been termed equine eosinophilic granuloma with collagen degeneration, nodular necrobiosis of collagen, and collagenolytic granuloma. The lesions are nodular, nonulcerative, and nonpruritic. They often occur in the saddle, central truncal, and lateral cervical areas and may have a gray-white central core. Older lesions may become mineralized. Histology reveals multifocal areas of collagen degeneration surrounded by granulomatous inflammation containing eosinophils. Thus, histologically, this lesion is similar to eosinophilic granuloma of cats and dogs. Treatment: In cats, hypersensitivity disorders (allergy to fleas, food, or inhalants) should be investigated by allergy testing and dietary elimination trials. Hyposensitization, insect control, and dietary management should be instituted when appropriate. Antibiotic therapy (amoxicillin-clavulanate, cefadroxil, or enrofloxacin) should always be tried empirically, especially in refractory cases. In dogs, antibiotics should also be tried initially. In horses, solitary lesions may be treated with systemic antibiotics, surgical excision, or sublesional corticosteroid injections. Mineralized lesions require excision. Seborrhea: Introduction Seborrhea is usually a chronic disease of dogs that is characterized by a defect in keratinization. Clinically, it results in increased scale formation, occasionally excessive greasiness of the skin and hair coat, and sometimes by secondary inflammation. Etiology, Clinical Findings, and Diagnosis: Primary seborrhea is an inherited skin disorder characterized by faulty keratinization of the epidermis, hair follicle epithelium, hair follicle cuticle, or the claw. The disease begins at a young age (usually <18-24 mo) and progresses
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throughout the dog's life. A diagnosis of generalized primary idiopathic seborrhea should be reserved for dogs in which all possible underlying causes of seborrhea have been ruled out. Most seborrheic dogs have secondary seborrhea, in which a primary underlying disease predisposes to excessive scaliness, crusting, or oiliness, often accompanied by superficial pyoderma and alopecia. The most common underlying causes are endocrinopathies and allergies. The goal is to identify and treat any underlying cause of the seborrhea. Other skin or systemic diseases may present with seborrhea as the primary clinical problem. The signalment (age, breed, sex) and history may provide clues in diagnosing the underlying cause. Allergies are more likely to be the underlying cause if the age of onset is <5 yr, whereas an endocrinopathy or neoplasia is more likely if the seborrhea begins in middleaged or older dogs. One of the most important points to consider is the degree of pruritus. If pruritus is minimal, endocrinopathies, other internal diseases, neoplasia, or certain diseases limited to the skin (eg, demodicosis or sebaceous adenitis) should be ruled out. If pruritus is significant, allergies and pruritic ectoparasitic diseases (eg, scabies, fleas) should be considered. The presence of pruritus does not rule out nonpruritic disease as the underlying cause, because the presence of a pyoderma or the inflammation from the free fatty acids involved with seborrhea can cause significant pruritus. However, the lack of pruritus helps to rule out allergies, scabies, and other pruritic diseases as the underlying etiology. Other important considerations include the presence of polyuria, polydipsia, or polyphagia; heat-seeking behavior; abnormal estrous cycles; attraction of the opposite sex; occurrence of pyoderma; the influence of seasonality; diet; response to previous medications (including corticosteroids, antibiotics, antihistamines, or topical treatments); zoonosis or contagion; and the environment. The dermatologic examination should document the type and distribution of the lesions; the presence of and type (complete or traumatic) of alopecia; and the degree of odor, scaliness, oiliness, and texture of the skin and hair coat. Hyperpigmentation indicates a chronic skin irritation (such as pruritus, infection, or inflammation), and lichenification indicates chronic pruritus. Superficial pyoderma plays a significant role in most seborrheic dogs. The sebum and keratinization abnormalities that are common in most seborrheic dogs frequently provide ideal conditions for bacterial infection. The self-trauma that occurs in pruritic animals increases the likelihood of a secondary bacterial infection. Often, coagulase-positive Staphylococcus spp are present. One of the first diagnostic steps is to perform impression smears of the affected areas to identify the quantity and type of bacteria present. If numerous cocci and neutrophils are present, pyoderma is likely. In addition to systemic antibiotic therapy, topical antibacterial shampoos will reduce the bacterial count on the surface of the skin and in the follicular lumen. After the pyoderma has been addressed, other diagnostic tests that should be considered include multiple deep skin scrapings, dermatophyte culture, impression smears, trichograms, and flea combing. If these are negative or normal, a CBC, serum biochemical profile, and complete urinalysis will complete the minimum database. Examples of diagnostic clues include increased serum alkaline phosphatase (which may suggest hyperadrenocorticism or previous steroid therapy), creatine phosphokinase or cholesterol (which may suggest hypothyroidism), blood glucose (which suggests diabetes mellitus), and BUN or creatinine (which may suggest renal disease). Treatment: Shampoo therapy is important in controlling seborrheic changes because seborrhea usually involves a large portion of the body and lends itself to topical treatment. Once the underlying disease has been identified, shampoos also help speed the return of the skin to a normal state. In the past, seborrhea has been classified as seborrhea sicca (dry seborrhea), seborrhea oleosa (oily seborrhea), or seborrheic dermatitis (inflammatory seborrhea). This scheme can still be used in determining the type of shampoo needed; however, most seborrheic animals have varying degrees of all three of these classifications of seborrhea. Most products contained in shampoos can be classified based on their effects as keratolytic, keratoplastic, emollient, antipruritic, or antimicrobial. Keratolytic products include sulfur, salicylic acid, tar, selenium sulfide, propylene glycol, fatty acids, and benzoyl peroxide. They remove stratum corneum cells by causing cellular damage that results in ballooning and sloughing of the surface keratinocytes. This reduces the scale and makes the skin feel softer. Shampoos containing keratolytic products frequently exacerbate scaling during the first 14 days of treatment, due to the sloughed scales getting caught in the hair coat. The scales will be removed by continued bathing, but owners should be warned that the scaling often worsens initially. Keratoplastic products help normalize keratinization and reduce scale formation by slowing down epidermal basal cell mitosis. Tar, sulfur, salicylic acid, and selenium sulfide are examples of keratoplastic agents. Emollients are used to hydrate the skin. Examples include lactic acid, sodium lactate, lanolin, and numerous oils, such as corn, coconut, peanut, and cottonseed. They are indicated for any scaling dermatosis because they act by reducing transepidermal water loss. They work best after the skin has been rehydrated and are excellent adjunct products after shampooing. Antibacterial agents include benzoyl peroxide, chlorhexidine, iodine, ethyl lactate, and triclosan. Antifungal ingredients include chlorhexidine, sulfur, iodine, ketoconazole, and miconazole. The selection of appropriate antiseborrheic shampoo therapy is based on hair coat and skin scaling and oiliness, of which there are four general presentations:
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mild scaling and no oiliness, moderate to marked scaling and mild oiliness (the most common), moderate to marked scaling and moderate oiliness, mild scaling and marked oiliness. These general categories are intended to guide, rather than dictate, the type of shampoo therapy necessary. All factors for each individual dog should be considered. Dogs with mild scaling and no oiliness need mild shampoos that are gentle, cleansing, hypoallergenic, or moisturizing. These shampoos are indicated for dogs that have mild seborrheic changes or that are irritated with medicated shampoos, or for owners that tend to overbathe. These products often contain emollient oils, lanolin, lactic acid, urea, glycerin, or fatty acids. Emollient sprays or rinses are often used in conjunction with these shampoos. Dogs with moderate to marked scaling and mild oiliness should be bathed with shampoos that contain sulfur and salicylic acid. Both agents are keratolytic, keratoplastic, antibacterial, and antipruritic. In addition, sulfur is antiparasitic and antifungal. Some of these shampoos also contain ingredients that are antibacterial, antifungal, and moisturizing, which can also help control secondary pyoderma, Malassezia spp , and excessive scaling. Shampoos that contain ethyl lactate lower the cutaneous pH (which has a bacteriostatic or bactericidal action by inhibiting bacterial lipases), normalize keratinization, solubilize fats, and decrease sebaceous secretions. These actions also result in potent antibacterial activity. Dogs with moderate to severe scaling and moderate oiliness often benefit most from tar-containing shampoos. Tar exerts potent keratoplastic effects by slowing basal epidermal cell DNA synthesis. It is often combined with sulfur and salicylic acid. Wood and coal are distilled to produce a tremendous variety of products called crude coal tars. Because of the variation in agents produced and techniques used to refine these products, exact comparisons of shampoos is difficult. More refined tars are usually less irritating and more stable but are more expensive to produce. More tar is not necessarily better. Only those tar products from reputable companies should be used. Tar shampoos usually have a distinct and unpleasant odor that lessens as the hair coat dries. Owner compliance is often diminished for products that have a prominent odor. In dogs with severe oiliness and minimal scaling, profound odor, erythema, inflammation, and a secondary generalized pyoderma or Malassezia dermatitis are often present. This group requires the most aggressive topical therapy. Shampoos that contain benzoyl peroxide provide strong degreasing actions along with potent antibacterial and follicular flushing activities. Because benzoyl peroxide shampoos are such strong degreasing agents, they can be irritating and drying. Other antibacterial shampoos are better suited in dogs that have superficial pyoderma without significant oiliness. As with tar, benzoyl peroxide has critical production requirements, and only refined products from reputable companies should be used. Most human products contain 5-10% benzoyl peroxide and should not be used because they are irritating to dogs. The follicular flushing action of benzoyl peroxide makes it ideal for dogs with numerous comedones or with demodicosis. Benzoyl peroxide gels (5%) are excellent choices when antibacterial, degreasing, or follicular flushing actions are desired for focal areas, such as in localized demodicosis, canine acne, or Schnauzer comedone syndrome.

1) 2) 3) 4)

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Metabolic Disorders Metabolic diseases are either inherited or acquired and acquired ones are more important. These diseases are of clinical significance because they affect energy production or damage tissues important for survival of the animal. Inherited Metabolic Disorders: Rare genetic disorders in many animals (Most commonly dogs & cats) result in inborn errors in metabolism. Animals are normal at birth but show clinical signs within the first few weeks or months of life. These diseases occur due to absence of enzymes critical in intermediary metabolism. These are progressive in nature and usually are fatal because of lack of specific treatments. Ex: Diseases associated with decreased RBC survival and anemia such as pyruvate kinase deficiency in Basenjis and Beagles, phosphofructokinase deficiency in English Springer Spaniels, and porphyria in cats. Congenital methemoglobinemia, hemophilia A, glucose-6-phosphate dehydrogenase deficiency, hyperkalemic periodic paralysis, and several immunodeficiences in horses. α-Mannosidosis in cattle and goat. goiter of sheep and goats, inherited parakeratosis (edema disease) of cattle, osteogenesis imperfecta of sheep and cattle, and possibly cardiomyopathy of cattle, the hypotrichoses, baldy calves, photosensitization of sheep, dermatosis vegetans and porcine stress syndrome of pigs, Acquired metabolic disorders: These diseases are primarily related to production or management and metabolism is a critical factor in the pathogenesis of each disease. For example hypocalcemia (Parturient paresis in cows), hypomagnesemia, and hypoglycemia, are promoted by management practices that are aimed at greater production. Hence they are entitled production diseases. However, they are also metabolic diseases because the demand for greater production is beyond the capacity of the animal's metabolic reserves to maintain the particular nutrient at physiologic concentrations. Most production-induced metabolic diseases result from a negative balance of a particular nutrient. In parturient paresis, the mammary secretion of calcium is greater than what either the diet or bone reserves can supply resulting in hypocalcemia. Exertional rhabdomyolysis of horses ( Azoturia and “Tying-up” or “Cording-up” Syndrome of Horses , Exertional Myopathy) occurs when a well fed otherwise inactive horse is put to work which results in the accumulation of lactic acid from excess muscle glycogen. There is a fine line between nutritional deficiencies and metabolic disorders. Nutritional deficiencies are chronic, steady state diseases corrected by dietary supplementation of the nutrient whereas metabolic disorders are rather acute and respond to systemic administration of the nutrient along with dietary supplementation to prevent reoccurrence. BOTTOMLINE: Metabolic disorders should be rapidly and accurately diagnosed. If possible it’s helpful to diagnose before the onset of clinical signs. Fatigue During Exercise: Introduction Muscular fatigue is manifest as a decrease in the ability of muscle to produce force. Fatigue occurs at both submaximal and maximal intensities of exercise, although the mechanisms of fatigue may vary greatly in athletic events of different intensity and duration. Fatigue during exercise can be due to pathological conditions, such as diseases affecting oxygen transport or neuromuscular function and, in such cases, work output will be less than expected. The following discussion is limited to causes of fatigue in normal, healthy exercising animals. Fatigue is a normal consequence of exercise and can be considered a safety mechanism. If fatigue did not occur, or were delayed greatly, it is likely that there would be structural damage to muscle cells and supportive tissues during intense exercise, as well as severe hyperthermia and dehydration during prolonged submaximal exercise. Studies of peripheral fatigue (fatigue due to altered muscle function Central fatigue is attributed to a decrease in performance because of a change in frequency of action potentials in motor neurons. It may occur secondary to pain, dyspnea, perceptions of exertion, hypoglycemia, hyperthermia, ammonia accumulation, and altered amino acid metabolism. Horses are capable of continuing endurance exercise despite severe hyperthermia, dehydration, and electrolyte disturbances, sometimes with fatal results. In general, the cause of fatigue during exercise depends greatly on the duration and energy demands of the event. Fatigue after High-intensity Exercise During brief, high-intensity exercise (<30 sec), anaerobic resynthesis of ATP predominates. Catabolism of ATP, creatine phosphate, and glycogen is the main source of energy in such events. Such exercise at an individual animal's highest attainable speed cannot be maintained for >30-40 sec. Thereafter, fatigue occurs and the animal slows down. Fatigue during such events is usually attributed to depletion of stores of creatine phosphate and to accumulation of lactate and protons in active muscle cells. Intracellular acidosis has a negative feedback effect on glycolytic enzymes and reduces the efficiency of the muscle contraction by interfering with the binding of calcium with troponin C, a vital step in excitationcontraction coupling. Recent research suggests that calcium accumulates in the sarcoplasm in such conditions, rather than
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being recycled through the sarcoplasmic reticulum (a process that requires ATP). Fatigue is also associated with depletion of creatine phosphate stores and accumulation of adenosine diphosphate (ADP) and inorganic phosphate. During exercise at maximal speeds lasting 2 min, intramuscular stores of ATP have been depleted by 50% in racehorses. The decline in intramuscular ATP was correlated with both the accumulation of lactate and the appearance of ammonia in the muscle. It has been postulated that ammonia accumulation in plasma may contribute to fatigue. Electrolyte disturbances in muscle may also play a role in fatigue after intense exercise. During intense exercise, water moves into muscle cells, and intracellular concentrations of potassium decrease, which is accompanied by increases in sodium and lactate concentrations. The net result is a reduction in the intracellular strong ion difference ([Na+ + K+ ] - [La + Cl-]) and acidosis. The decrease in intracellular potassium concentration, increase in concentration of potassium in the extracellular fluid, and accumulation of sodium in the sarcoplasm tends to depolarize sarcolemma and t-tubule membranes, which decreases the strength of muscle contractions. It has been suggested that accumulation of calcium and depletion of ATP in muscle cells during exercise induces more rapid potassium efflux from muscle cells. This may inactivate the sarcolemma and t-tubule membranes and prevent tension development. Synchronous diaphragmatic flutter (SDF, Murmurs and other Abnormal Sounds) is sometimes seen after races in Thoroughbreds and Standardbreds, although it is more usually associated with fatigue during prolonged exercise in horses. Its occurrence in horses after races of 2-3 min duration suggests that it may be related to electrolyte disturbances. SDF can occur in Standardbreds after a particularly strenuous race, and it resolves after 30-60 min without treatment. Fatigue after Prolonged Exercise During prolonged exercise lasting many hours, heat generated in the course of mainly aerobic ATP resynthesis imposes a thermoregulatory demand on the animal. Responses include sweating and panting. The result is dehydration and acid-base and electrolyte disturbances, and these factors are usually implicated in the fatigue, exhaustion, and even death that can occur after such exercise. Fatigue during prolonged exercise has also been associated with depletion of glycogen stores in muscle and liver and with hypoglycemia. Prevention of Fatigue Training: Physical training is the most effective way of reducing fatigue and increasing the ability to exercise. There are many physiological responses to training, including increases in the maximal rate of oxygen transport, stroke volume, capillary density in muscle, blood volume, and total Hgb content of blood. Hypertrophy of muscle cells occurs, along with increases in concentrations of mitochondria, glycogen, and enzymes concerned with energy production. Sprint training can result in decreased proportions of slow-twitch fibers, and endurance training can result in increased oxidative capacity of fast-twitch fibers. Training also increases the strength of supportive tissues (such as ligaments, tendons, and bones) and decreases the likelihood of muscle soreness in response to exercise. Training therefore results in functional and structural adaptations that enable an animal to run faster or longer. Nutrition: Energy supply and hydration are frequently manipulated in human athletes to limit fatigue during endurance exercise. Dehydration before exercise results in higher core temperatures during exercise in horses. It would be inappropriate for an animal to begin endurance exercise with suboptimal hydration or glycogen concentrations in liver and muscle. Whether or not hyperhydration before exercise or carbohydrate “loading” has a role in endurance exercise in animals is unknown. Horses are more susceptible to hyperthermia during prolonged exercise because of their high body mass to surface area ratio. Glucose supplementation may be important in limiting fatigue in endurance exercise in horses. This may be due to increased glucose availability, reduced reliance on anaerobic energy production, lower core temperature, and better maintenance of plasma volume. Horses should not be given large meals 1-2 hr before competition because plasma volume is decreased for at least 1 hr after a large meal. Feeding small portions every 4 hr does not affect plasma volume. The use of fat as a dietary supplement in horses has been suggested to increase performance. Carnitine supplements have been used in the expectation of faster rates of fat metabolism in muscle. Buffering agents, such as sodium bicarbonate, have been popular as ergogenic aids, especially in horse racing. Exhaustion Horses that have competed in 3-day events or endurance rides may present with life-threatening exhaustion. Horses may lose sweat at 10-15 L/hr during prolonged exercise, and urgent treatment of fluid and electrolyte deficits and hyperthermia (rectal temperatures >40.5° C) may be required. Isotonic balanced electrolyte solutions can be administered PO and IV for dehydration. Initially, 8 L can be given PO, followed by subsequent administration of 4-8 L every 1-2 hr. Hypertonic, hypotonic, or alkaline solutions should not be used. About 30 L of Ringer's solution is required to replace a sodium deficit of 4000 mmol.
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Synchronous diaphragmatic flutter can occur after endurance rides and often resolves spontaneously. However, it can be treated by administering 5% calcium borogluconate slowly to effect. Fatty Liver Disease Of Cattle: Introduction (Fat cow syndrome) Fatty liver is most common in periparturient cattle. Although often considered a postpartum disorder, it usually develops before and during parturition. Endocrine changes associated with parturition and lactogenesis contribute to the development of fatty liver. Inappetence almost always accompanies severe cases. Cows that are overconditioned at calving are most likely to develop fatty liver, and cows that develop fatty liver at calving are most susceptible to ketosis. Fatty liver can occur whenever there is a decrease in feed intake and may be secondary to the onset of another disorder. Etiology: Fatty liver occurs during periods when blood concentrations of nonesterified fatty acids (NEFA) are increased. The most dramatic increase occurs at calving when plasma concentrations often exceed 1000 µEq/L. Concentrations can reach that level if the cow goes off feed. Uptake of NEFA by the liver is proportional to NEFA concentrations in the blood. NEFA taken up by the liver can either be oxidized or esterified. The primary esterification product is triglyceride, which either can be exported as part of a low-density lipoprotein, or stored. In ruminants, export occurs at a very slow rate relative to many other species. Therefore, under conditions of increased hepatic NEFA uptake and esterification, triglyceride accumulation occurs. Oxidation of NEFA leads to the formation of CO2 and ketones, primarily acetoacetate and β-hydroxybutyrate. Ketone formation is favored when blood glucose concentrations are low. Conditions that lead to low blood glucose also contribute to fatty liver because insulin suppresses fat mobilization from adipose tissue. The greatest increase in liver triglyceride typically occurs at calving. The extent to which feed intake is depressed before and after calving or during disease moderates the degree of infiltration of triglycerides. Fatty liver can develop within 24 hr of an animal going off feed. Because of the slow rate of triglyceride export as lipoprotein, once fatty liver has developed, it will persist for an extended period of time. Depletion of triglycerides from the liver usually begins when the cow reaches positive energy balance and may take several weeks to be completed. Fatty liver is a consequence of negative energy balance, not positive energy balance. Triglyceride deposition will occur only if the cow becomes overconditioned and, consequently, reduces feed intake. Fatty liver is likely to develop concurrently with another disease, typically disorders that are seen at or shortly after calving, including metritis, mastitis, displaced abomasum, acidosis, and hypocalcemia. Cows that are slow to increase in milk production and feed intake after calving are likely to have fatty liver. However, fatty liver is probably the result of poor feed intake rather than the cause. Fatty liver is often associated with obese cows and downer cows ( Problematic Bovine Sternal Recumbency: Introduction). Clinical Findings and Diagnosis: There are no known clinical signs that are unique to cows with fatty liver. Fatty liver has been associated with low milk production, increased clinical mastitis, and poor reproductive performance. However, cause and effect have not been established, and the metabolic consequences of triglyceride accumulation in the liver has not been determined. Liver biopsy is the only reliable method to determine severity of fatty liver in dairy cattle. Blood glucose concentrations are low and blood NEFA and β-hydroxybutyrate concentrations are high when conditions are conducive to the development of fatty liver. Blood cholesterol concentration is usually low when fatty liver occurs, and this may reflect an impairment in the ability of the liver to secrete lipoproteins. Aspartate transaminase, ornithine decarboxylase, and sorbitol dehydrogenase are hepatic enzymes that may be positively associated with liver triglyceride and liver damage. Prevention and Treatment: Reducing the severity and duration of negative energy balance is crucial in the prevention of fatty liver. This can be achieved by avoiding overconditioned cattle, rapid diet changes, unpalatable feeds, periparturient diseases, and environmental stress. Cows within a herd should enter the dry period with an average body condition score of 3-3.5 (scale15). Thin cows (body condition score of ≤2.5) can be fed additional energy during the dry period to improve condition without fear of causing fatty liver. Overconditioned cattle (body condition score of ≥4.0) should not be feed restricted because this will promote fat mobilization and increase blood NEFA and liver triglyceride. The critical time for the prevention of fatty liver is ~1 wk before to 1 wk after calving, which is when the cow is most susceptible to development of fatty liver. Cows that are candidates for preventive measures are those that are overconditioned or are starting to go off feed. Glucose or compounds that can be converted to glucose by the liver can be administered IV. Propylene glycol, 10-30 oz, given as an oral drench once daily during the final week prepartum has been effective in reducing plasma NEFA and the severity of fatty liver at calving. Sodium propionate is also a glucose precursor, but feeding can cause a depression in feed intake and reduce efficacy. Glucose or glucose precursors are effective because they may cause an insulin response. Insulin is antilipolytic, ie, it decreases lipid mobilization from adipose tissue. IM injections of a slow-release insulin compound may be effective. Niacin is an antilipolytic agent that may have potential for prevention of fatty liver.
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Minimizing stress is important for the prevention of fatty liver. There is no proven treatment for fatty liver. Hypocalcemic Tetany In Horses: Introduction (Transport tetany, Lactation tetany, Eclampsia) Hypocalcemic tetany in horses is a rare condition associated with acute depletion of serum ionized calcium and sometimes with alterations in serum concentrations of magnesium and phosphate. It occurs after prolonged physical exertion or transport (transport tetany) and in lactating mares (lactation tetany). Signs are variable and relate to neuromuscular hyperirritability. Etiology: Prolonged stress and excess calcium losses in milk or sweat may result in clinical signs of hypocalcemia. In lactating mares, high milk production and grazing of lush pastures appear to be predisposing factors. Hypocalcemia after prolonged physical activity (eg, endurance rides) results from sweat loss of calcium, increased calcium binding during hypochloremic alkalosis, and stress-induced high corticosteroid levels. Corticosteroids inhibit vitamin D activity, which leads to decreased intestinal absorption and skeletal mobilization of calcium. Stress and lack of calcium intake have been associated with transport tetany. Clinical Findings: The severity of clinical signs corresponds with the serum concentration of ionized calcium. Increased excitability may be the only sign in mild cases. Severely affected horses may show behavioral changes such as anxiety, increased muscle tone, prolapse of the third eyelid, high tail carriage, stiffness of gait or hindlimb ataxia, muscle fasciculations, trismus, dysphagia, salivation, anxiety, profuse sweating, fever, tachypnea, tachycardia, cardiac arrhythmias, synchronous diaphragmatic flutter, convulsions, coma, and death. In lactating mares, if not treated, the disease may take a progressive and sometimes fatal course over 24-48 hr. Differential diagnoses include tetanus, endotoxemia, colic, exertional rhabdomyolysis or other muscle disorder, seizure disorder, laminitis, and botulism. Diagnosis: A tentative diagnosis is made based on clinical signs, history, and response to treatment. Definitive diagnosis requires demonstration of low serum levels of ionized calcium. Most laboratories measure only total (protein-bound and free) serum calcium, which is an acceptable diagnostic test in most cases. However, discrepancies may arise in alkalotic and hypoalbuminemic horses. Alkalosis increases albumin binding of calcium, which results in a decreased concentration of ionized calcium. Thus, alkalotic horses may have normal total serum calcium while exhibiting signs of hypocalcemia. Likewise, hypoalbuminemic or acidotic horses may have decreased total serum calcium without developing signs of hypocalcemia. Treatment: IV administration of calcium solutions, such as 20% calcium borogluconate or those recommended for treatment of periparturient paresis in cattle, usually result in full recovery. Prevention: Feeding a low-calcium diet, such as grass forage and cereal grain, at least 2-3 wk before the time when hypocalcemia is likely to occur (ie, before prolonged transportation or lactation) may be beneficial. This will stimulate active intestinal absorption and skeletal mobilization of calcium necessary to maintain calcium homeostasis in the event of a sudden demand for increased calcium. In times of increased calcium demand, a good source of dietary calcium, such as alfalfa and calciumcontaining mineral mixes, should be provided to the horse to prevent hypocalcemia. In endurance horses, water and electrolyte deficits associated with prolonged exercise and sweating may be prevented by provision of a sufficient water supply and electrolyte supplementation. Hypomagnesemic Tetany In Cattle And Sheep: Introduction (Grass tetany, Grass staggers) Hypomagnesemic tetany is a complex metabolic disturbance characterized by hypomagnesemia (plasma magnesium <1.5 mg/dL [<0.65 mmol/L]) and a reduction in the concentration of magnesium in the CSF (<1.0 mg/dL [0.5 mmol/L]), which lead to hyperexcitability, muscular spasms, convulsions, and death. Adult lactating animals are most susceptible due to the loss of magnesium in milk. Hypomagnesemic tetany occurs mainly when animals are grazed on lush pastures but can occur in lactating beef cows fed silage indoors. It is rare in nonlactating cattle but has occurred when undernourished cattle were introduced to green cereal crops. Etiology: The disorder occurs after a decrease in plasma magnesium concentration when absorption of dietary magnesium is unable to meet the requirements for maintenance (3 mg/kg body wt) and lactation (120 mg/kg milk). This can arise after a reduction in food intake during inclement weather, transport, or when cows graze short grass dominant pastures containing <0.2% magnesium on a dry-matter basis. Low herbage availability (<1000 kg dry matter per hectare) results in liveweight
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losses during lactation, and plasma magnesium decreases because insufficient magnesium is obtained from body tissues mobilized during loss of liveweight to support lactation. Magnesium absorption from the rumen may be reduced when potassium and nitrogen intakes are high, and sodium and phosphorus intakes are low. Cows with hypomagnesemia often do not develop grass tetany until blood calcium concentrations decrease below 8 mg/dL (2.00 mmol/L), which commonly occurs in cattle grazing green cereal crops. The hypocalcemia arises from either a reduction in calcium intake or absorption, or both. Lush pastures and green cereal crops may predispose cattle to metabolic alkalosis (urine pH >8.5) with a reduced available pool of calcium, thereby increasing the risk of hypocalcemia. Urine magnesium concentrations are a useful guide to magnesium status and are undetectable in cows with hypomagnesemia. Clinical Findings: In the most acute form, affected cows, which may appear to be grazing normally, suddenly throw up their heads, bellow, gallop in a blind frenzy, fall, and exhibit severe paddling convulsions. These convulsive episodes may be repeated at short intervals, and death usually occurs within a few hours. In many instances, animals at pasture are found dead without observed illness, but an indication that the animal had convulsions before death may be seen from the marks on the ground. In less severe cases, the cow is obviously ill at ease, walks stiffly, is hypersensitive to touch and sound, urinates frequently, and may progress to the acute convulsive stage after a period as long as 2-3 days. This period may be shortened if the cow is transported or driven to a fresh pasture. When animals have hypocalcemia and hypomagnesemia, the signs shown depend on which predominates. With hypomagnesemia, tachycardia and loud heart sounds are characteristic signs. Treatment: Animals showing clinical signs require treatment immediately with combined solutions of calcium and magnesium, preferably given IV and slowly while monitoring the heart (see parturient paresis, Parturient Paresis In Cows: Introduction). The animal should not be stimulated during treatment because this could trigger fatal convulsions. Prevention: Magnesium has to be given daily to animals at risk because there is no readily available store in the body. Daily oral supplements of magnesium oxide (2 oz [60 g] to cattle and 1/3 oz [10 g] to sheep) should be given in the danger period. Most magnesium salts are unpalatable and must be combined with other palatable ingredients such as molasses, concentrates, or hay. Ketosis In Cattle: Introduction (Acetonemia, Ketonemia) Ketosis is a metabolic disease of lactating dairy cows characterized by weight loss, pica, inappetence, decreased milk production, and neurologic abnormalities that usually occur during the first 6 wk of lactation. Ketosis occurs worldwide whenever dairy cows are selected and fed for high milk production. It affects both primiparous and multiparous cows. Incidence is highest during the third and fourth weeks of lactation in closely confined stabled dairy cows that are improperly fed and conditioned during the dry period and early lactation. Ketosis can occur whenever a cow goes off feed for any reason. Significant predisposing and concomitant conditions are retained fetal membranes, metritis, mastitis, displaced abomasa, fatty livers, environmental stresses, faulty nutrition, and mismanagement. Etiology and Pathogenesis: Ketosis is basically the result of a negative energy balance in the 6 wk after parturition. The cow is unable to eat or assimilate enough nutrients to meet her energy needs for maintenance and milk production during this period. Therefore, blood glucose levels drop and hypoglycemia results. In an effort to correct this condition, body fat and limited protein stores are mobilized in the form of triglycerides and amino acids for gluconeogenesis. Ketone bodies (acetoacetic acid, acetone, and β-hydroxybutyric) are produced during the mobilization process. This occurs to a limited degree in practically all highproducing cows in early lactation, and only a subclinical ketosis develops if the herd is properly fed and conditioned and free of predisposing factors. Ketone bodies are produced primarily in the liver but also in smaller quantities in the mammary gland and rumen wall. Clinical Findings: Onset of signs is usually gradual, and close observation is required to determine their presence. Initial signs include a slight decrease in feed intake, drop in milk production, lethargy, and firm mucus-covered stools. As the disease progresses, a marked weight loss occurs that may approach several hundred pounds in a few days. Pica is often seen in which affected cows refuse grain and seek coarse materials such as coarse hay, straw, ground, and even tree twigs. As the disease progresses, depression deepens, movement is limited, and cows stand with a humpbacked posture. There may be an acetone odor to the breath, urine, or milk. Although most cows exhibit the lethargic wasting signs, some show frenzy and aggression. They may compulsively lick metal stanchions, mangers, or their own bodies. Head or nose pressing may occur along with chewing and bellowing. Walking may be abnormal with staggering, circling, and falling. Some cows seriously injure themselves during these activities, and death may result. If ketosis is untreated, milk production decreases to an insignificant amount that does not require much energy to produce.
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Lesions: Although few cows die of primary ketosis that is not complicated with predisposing factors, ketosis does produce some pathology. The carcass is thin and malnourished with little body fat, indicative of starvation. The liver, kidneys, and heart are likely to show fatty infiltration. The liver is most seriously affected and is often pale yellow and may be soft and friable; in severe and prolonged cases, it may be necrotic. The adrenals are often enlarged, flabby, and infiltrated with fat. Regressive changes in the pituitary gland, acute involution of the pancreas, and fattened epithelial cells in the thyroid gland have also been reported. Diagnosis: It is extremely important to obtain a complete history when ketosis is suspected. All cows suspected of having ketosis should receive a thorough physical examination along with Rothera's test for ketone bodies. Rothera's test for ketones is usually conducted on urine but because ketones are so highly concentrated in urine (up to 1200 mg/dL), vary widely due to urine concentration, and are normally present in early lactation high-producing cows, a positive urine test is usually not considered to be diagnostic of clinical ketosis. Because ketone levels in milk are much lower (usually not exceeding 50 mg/dL in clinical cases) and less variable, a positive Rothera's test of milk is considered to be a much more accurate diagnosis of clinical ketosis. Blood glucose levels are also helpful in arriving at a diagnosis. Normal levels of 40-60 mg/dL drop to below 25 mg/dL in clinical ketosis. Differential diagnoses should include but not be limited to hypocalcemia, retained fetal membranes, metritis, indigestion, abomasal displacement, traumatic reticulitis, poisoning, pyelonephritis, listeriosis, and rabies. Treatment: Routine treatment is IV administration of 500 mL of 50% glucose and IM administration of the glucocorticoid of choice. Propylene glycol (225 g, b.i.d. for 2 days, followed by 100 g daily for 2 days) or other glucose precursors are also administered PO in many cases. After glucocorticoid therapy, blood glucose levels return to normal in 8-10 hr and behavior improves markedly within 24 hr. Milk production may temporarily decrease after glucocorticoid administration but increases rapidly after several days. Prevention: Cows should be properly conditioned during late lactation and the dry period. They should be fed so that body score at calving will be 3.5 on a 5-point scale. About 2 wk before parturition, cows should be started on a small amount of the concentrate ration they will receive during early lactation. The amount of concentrate should be gradually increased so that at parturition, the cow will be consuming 1 lb per 150 lb body wt daily. In problem herds, it is usually helpful to limit silage and increase long hay in the ration. Malignant Hyperthermia : Introduction (Porcine stress syndrome) Malignant hyperthermia (MH) is a hypermetabolic syndrome involving the skeletal muscle characterized by muscle rigidity, hyperthermia, dyspnea, dysrhythmias, and death. It has been reported in most swine breeds, but prevalence varies with values exceeding 90% in some breeds and strains. Prevalence of MH is higher in lean, heavily muscled breeds, eg, Pietrain, Poland China, Landrace, and Duroc. Etiology: Susceptibility to MH is determined by an autosomal recessive gene that has variable penetrance. The causative mutation has been localized to a C-to-T transition in the gene that controls the Ca2+ release channel (ryanodine receptor) of sarcoplasmic reticulum in skeletal muscle. MH is triggered by exposure of susceptible animals to volatile anesthetics or depolarizing muscle relaxants and, in the case of porcine stress syndrome, by exertional or environmental stressors. Subsequent to the initial challenge or stress, the hypersensitive ryanodine receptor floods the myoplasm of skeletal muscle with Ca2+. Muscle contracture and hypermetabolism develop rapidly as a direct result of this uncontrolled and sustained increase in myoplasmic Ca2+. ATP depletion in skeletal muscle occurs as energy requirements for contracture exceed supply. Increased aerobic and anaerobic metabolism results in excessive CO2 and lactic acid production, while thermogenesis and peripheral vasoconstriction increase core body temperature. As the MH episode progresses, the combination of increased temperature, acidosis, and ATP depletion leads to rhabdomyolysis. Myoplasmic enzymes and electrolytes are released from the cell, and additional Ca2+ enters the myoplasm. Contracture and its subsequent energy requirements are further enhanced and eventually, due to temperature and pH changes, contracture proceeds independently of myoplasmic Ca2+ levels. Death occurs due to an increase in serum K+, which causes cardiac dysrhythmia and arrest. Clinical Findings: The rapidity with which clinical signs develop varies. Signs include muscle stiffness or fasciculations, which progress to muscle rigor. Sinus tachycardia develops early and continues until serum K+ reaches cardiotoxic levels. Open-mouthed breathing, tachypnea, and hyperventilation, which progress to apnea, are also seen. Blanching and erythema of the skin followed by blotchy cyanosis is seen in light-colored animals. Core body temperature rapidly increases and can reach 113°F

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(45°C) antemortem. After death, rigor mortis quickly develops and muscle temperature is significantly increased. Affected muscles from an animal that dies acutely are pale and soft and appear exudative or wet. Diagnosis: Clinical diagnosis is based on development of clinical signs in an animal exposed to a volatile anesthetic or to some stressful event. The acute nature of the disease and its relationship to a stressor enables differentiation of MH from other fatal disorders of swine. Treatment: Often, MH episodes are not treated in the field. If undertaken, treatment must be instituted rapidly or the animal will die. First, exposure of the animal to the volatile anesthetic or stressor must be eliminated, and then dantrolene sodium at 4-5 mg/kg, IV, should be given. Dantrolene must be administered early in the course of the disease because muscle blood flow is significantly reduced as the disease progresses. Other supportive measures include oxygen enrichment of inspired gases and treatment of cardiac dysrhythmias. Control: Reducing the prevalence of MH within the swine population requires genetic selection against the trait. There is concern that some breeds may, in fact, not survive if there were an active selection program to eliminate MH from the population. Parturient Paresis In Cows: Introduction (Milk fever, Hypocalcemia) Parturient paresis is an afebrile disease of mature dairy cows that occurs most commonly at or soon after parturition and is manifest by changes in mentation, generalized paresis, and circulatory collapse. Etiology: At or near the time of parturition, the onset of lactation results in the sudden loss of calcium through milk. Serum calcium levels decline from a normal of 10-12 mg/dL to 2-7 mg/dL. Commonly, serum magnesium is increased, serum phosphorus is decreased, and cows are hyperglycemic. The disease may occur in cows of any age but is most common in high-producing dairy cows >5 yr old. Incidence is higher in the Jersey breed. Clinical Findings and Diagnosis: Parturient paresis usually occurs within 72 hr of parturition. The disease can contribute to dystocia, uterine prolapse, and retained fetal membranes. There are three discernible stages of parturient paresis. During stage one, cows are able to stand but show signs of hypersensitivity and excitability. Cows may be slightly ataxic, have fine tremors over the flank and loins, and display ear twitching and head bobbing. Cows may appear restless, shuffling their rear feet and bellowing. If calcium therapy is not instituted, cows will progress to stage two. In stage two, cows are unable to stand but can maintain sternal recumbency. Depression, anorexia, dry muzzle, subnormal body temperature, and cold extremities are seen. Auscultation reveals tachycardia and decreased intensity of heart sounds. Smooth muscle paralysis leads to GI stasis, which can be manifest as bloat, failure to defecate, and loss of anal sphincter tone. Ability to urinate can also be lost. Cows often tuck their heads into their flanks or, if the head is extended, an S-shaped curve to the neck may be noted. In stage three, cows lose consciousness progressively to the point of coma. They are unable to maintain sternal recumbency, have compete muscle flaccidity, are unresponsive to stimuli, and can suffer severe bloat. As cardiac output worsens, heart rate can approach 120 beats/min, and pulse may be undetectable. Cows in stage three may survive only a few hours. Differential diagnoses include toxic mastitis, toxic metritis, other systemic toxic conditions, traumatic injury (eg, stifle injury, coxofemoral luxation, fractured pelvis, spinal compression, etc), obturator paralysis, or compartmental crush syndrome. Treatment: Treatment is directed toward restoring the serum calcium level to normal as soon as possible to avoid muscular and nervous damage and recumbency. Recommended treatment is IV injection of a calcium gluconate salt, although SC and IP routes are also used. A general rule for dosing is 1 g calcium/45 kg (100 lb) body wt. Solutions containing formaldehyde or >25 g dextrose/500 mL are irritating if given SC. Many solutions contain phosphorus and magnesium in addition to calcium. Although the administration of phosphorus and magnesium is not usually necessary in uncomplicated parturient paresis, detrimental effects of their use have not been reported. Magnesium may protect against myocardial irritation caused by the administration of calcium. Calcium is cardiotoxic; therefore, calcium-containing solutions should be administered slowly (10-20 min) while cardiac auscultation is performed. If severe dysrhythmias or bradycardia develop, administration should be stopped until the heartbeat has returned to normal. Endotoxic animals are especially prone to dysrhythmias caused by IV calcium therapy.

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Administration of oral calcium avoids the risks of cardiotoxic side effects and may be useful in mild cases of parturient paresis. Calcium propionate in propylene glycol gel is effective and avoids the potential for metabolic acidosis caused by calcium chloride. Hypocalcemic cows typically respond to therapy immediately. Tremors are seen as neuromuscular function returns. Improved cardiac output results in stronger heart sounds and decreased heart rate. Prevention: Administration of vitamin D3 and its metabolites is effective in preventing parturient paresis. Use of synthetic bovine parathyroid hormone (PTH) may prove to be superior to vitamin D metabolites. Vitamin D metabolites enhance GI calcium absorption, whereas PTH enhances GI calcium absorption and stimulates bone resorption. PTH is administered either IV 60 hr before parturition, or IM 6 days before parturition. Parturient Paresis In Ewes: Introduction Parturient paresis in pregnant and lactating ewes is a disturbance of metabolism characterized by acute hypocalcemia and rapid development of hyperexcitability, ataxia, paresis, coma, and death. Etiology: Deficiency of calcium or magnesium, or both, may be contributing factors. The disease occurs at any time from 6 wk before lambing to 10 wk after, principally in highly conditioned older ewes at pasture. Clinical Findings and Diagnosis: The earliest signs are slight hyperexcitability, muscle tremors, and a stilted gait. These are soon followed by dullness, sternal decubitus (often with the hindlegs extended backward), mild ruminal tympany and regurgitation of food through the nostrils, staring eyes, shallow respiration, coma, and death within 6-36 hr. Diagnosis is based on the history and clinical signs. In outbreaks occurring before lambing, pregnancy toxemia ( Pregnancy Toxemia In Ewes: Introduction) is the main differential diagnosis. A tentative diagnosis of acute hypocalcemia can be confirmed readily by a dramatic and usually lasting response to calcium therapy. Prevention and Treatment: Treatment consists of IV or SC calcium (eg, 100 mL of 25% w/v calcium borogluconate), preferably with some added magnesium. Affected sheep should be handled with care, lest sudden deaths occur from heart failure. Prevention is largely a matter of avoiding the predisposing causes. Postparturient Hemoglobinuria: Introduction Cows affected with this disease of rapid intravascular hemolysis develop severe anemia and weakness, and milk production drops markedly. The disease occurs worldwide. The exact cause is unknown, but the most likely predisposing factors are phosphorus deficiency, which increases osmotic fragility of erythrocytes (in North America), and copper deficiency, which increases susceptibility of erythrocytes to oxidative injury (in New Zealand). In both locations, hemolytic or oxidative plant toxins (often from Brassica spp , sugar beets, or green forage), selenium deficiency, and ketoacidosis probably contribute. In North America, the disease is sporadic and common in older, high-producing dairy cows, while in New Zealand, herd outbreaks occur involving cows of all ages. Beef and nonlactating cattle are rarely affected. Clinical disease is rare but, when it occurs, the case fatality rate is high. The incidence of subclinical disease is unknown; many postparturient dairy cows have blood or hemoglobin in their urine, and the source is rarely established. With clinical disease, rapid intravascular hemolysis leads to severe anemia, tachycardia, weakness, hemoglobinuria, and pallor over several days. Milk production drops rapidly over sequential milkings. Affected cows also may have fever, diarrhea, and tachypnea. Diagnosis is usually made by recognition of clinical signs. Hemoglobinuria may best be established by failure of the urine to clear with centrifugation (ruling out hematuria) and presence of concurrent severe anemia (making hemoglobinuria more likely than myoglobinuria). Intravascular hemolysis caused by Babesia ( Babesiosis: Overview) or Theileria ( Theileriases: Overview) may be ruled out by blood film analysis, and standard laboratory methods can be used to rule out leptospirosis ( Leptospirosis in Cattle , Leptospirosis) or bacillary hemoglobinuria ( Bacillary Hemoglobinuria , Bacillary Hemoglobinuria). Diagnostic testing and feed or pasture analysis can be performed to identify toxic plants and deficiency of phosphorus or copper. Transfusion of large quantities of whole blood is the best treatment for severely affected cows. Crystalloid fluids may be beneficial if blood is not available. Treatment with sodium acid phosphate (60 g in 300 mL of sterile water, IV followed by SC, every 12 hr) or copper glycinate (120 mg available copper) may halt hemolysis in cases in North America and New Zealand, respectively. Correction of mineral deficiencies and elimination of plant toxins from the diet may help prevent recurrence. Pregnancy Toxemia In Cows: Introduction Pregnancy toxemia in cattle is similar to the condition in small ruminants and is the result of fetal carbohydrate or energy demand exceeding maternal supply during the last trimester of pregnancy. It is precipitated by large or multiple
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fetuses, feed low in energy or protein, and health conditions that increase energy demand or decrease ability to take in nourishment (notably lameness and oral diseases). The fetoplacental unit is an obligate user of carbohydrate for energy and removes these compounds from the blood in an insulin-independent fashion. When this demand exceeds maternal supply, adipose tissue is mobilized to supply energy as acetate or ketone bodies, sparing carbohydrate consumption by other maternal tissues. However, only a small amount of new carbohydrate is generated from fat metabolism (from glycerol). This condition is more severe than ketosis ( Ketosis In Cattle: Introduction) because fetal demand increases during pregnancy, while milk demand can decline in response to negative energy balance. Although the mechanism is unknown, clinical disease develops in some cows with negative energy or carbohydrate balance. Proposed mediators of clinical disease include glucose deficiency with intermittent hypoglycemia, ketone body accumulation with metabolic acidosis or appetite suppression, and death of the fetus with secondary infection and toxemia. Individual cows of any breed can be affected, but herd problems are most common in beef cattle, which frequently are managed so that late pregnancy coincides with the poorest availability of feed. Both thin and fat cows can be affected, but the first noted abnormality often is loss of body condition over 1-2 wk. Decreased appetite, rumination, fecal production, and nose-licking are general signs of illness. With time, affected cows become markedly depressed, weak, ataxic, and recumbent. Opisthotonos, seizures, or coma may be seen terminally. Ketonuria is present from the early stage of disease and is the most specific finding; even mild ketonuria should not be found in normal pregnant cows until a few days before calving. Hypoglycemia is also common, but excited or seizuring cows may have hyperglycemia. With more advanced disease, there may be variable increases in serum activities of muscle or liver enzymes, as well as clinicopathologic evidence of infection, metabolic acidosis, internal organ dysfunction or failure, and circulatory collapse. Hepatic lipidosis in conjunction with large or multiple fetuses is the most common necropsy finding; evidence of muscle pressure necrosis and toxemia may also be found. Successful treatment requires early identification of the disease. There are few diagnostic rule-outs, and pregnancy toxemia must be considered a factor in any disease that affects cattle in late gestation. Cattle that have weight loss but are still appetent may be managed by feeding concentrate or propylene glycol (0.5-1 g/kg/day). Cattle that are anorectic must be treated aggressively, because the decrease in energy intake causes the disease to progress rapidly. Propylene glycol can be force-fed or dextrose given IV (0.5 g/kg). Cattle with dehydration, organ dysfunction, or metabolic acidosis should be treated with large volumes (20-60 L/day, PO or IV) of electrolyte fluids; if IV fluid administration is practical, continuous dextrose infusion (5%) is recommended. Protamine zinc insulin (200 u, SC, every 48 hr) may be given after dextrose administration to suppress ketogenesis. Recumbent cattle may benefit from good nursing care (see downer cow, Problematic Bovine Sternal Recumbency: Introduction) but rarely respond to treatment. To decrease the energy drain of any cow with pregnancy toxemia, induction of parturition or removal of the fetus by cesarean section should be considered. On the herd level, the disease can be prevented by adequate attention to nutrition and health care of cattle in late gestation. For the individual cow, recognition of the precarious state of energy and carbohydrate balance during late gestation dictates careful monitoring of energy intake, attitude, and fat mobilization, especially during times of illness.

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Musculoskeletal System The transmission of a nerve impulse at the neuromuscular junction involves massive release of acetylcholine from small synaptic vessels, where it is stored. The acetylcholine fills the synaptic cleft between the nerve terminal and the muscle fiber membrane, where most of it is destroyed by cholinesterase within a fraction of a second. This short period of activity is sufficient to excite the muscle fiber membrane, which results in a significant increase in membrane permeability to sodium ions and allows rapid influx of sodium into the muscle fiber. The sodium ion increases the endplate potential, which elicits electrical currents that spread to the interior of the fibers where they cause a release of calcium ions from the sarcoplasmic reticulum. The calcium ions initiate, in turn, the chemical events of the contractile process. When this occurs in all the muscle fibers innervated by each motor neuron (possibly thousands), muscle contraction results. Disorders that affect the neuromuscular junction (eg, myasthenia gravis, hypocalcemia, hypermagnesemia) can result in muscle fatigue, weakness, and paralysis. The neuromuscular junction can also be affected by muscle-relaxing drugs (eg, curare, succinylcholine, M99), certain antibiotics, and toxins (eg, botulism, tetanus, venoms). Disorders primarily of the muscle membrane and, to some extent, of the actual muscle fibers are called myopathies. Muscle membrane disorders may be hereditary (eg, myotonia congenita in goats) or acquired (eg, vitamin E and selenium deficiencies, hypothyroidism, and hypokalemia). Bone diseases are generally congenital or hereditary, nutritional, or traumatic. Articulations are divided into synarthroses, in which the osseous components are united by fibrous tissue or cartilage, and diarthroses, in which the opposing bone ends are covered with hyaline cartilage and are separated by a joint cavity filled with synovial fluid. Synarthoses are practically immovable and are rarely associated with joint disease other than fractures. In most cases, diarthroses are movable joints, with a variable degree of mobility depending on the anatomic location of the joint. Chronic inflammation of joints and surrounding structures is most common in articulations associated with locomotion, although other joints, such as the temporomandibular, may occasionally be affected as well. Normal synovial fluid lubricates the synovial tissues in a joint through boundary lubrication, whereas articular cartilage lubrication is provided by weeping lubrication, through a glycoprotein expressed from the cartilage during weight bearing. Arthritis: Overview Arthritis is a nonspecific term denoting inflammation of a joint. All joint diseases of large animals have an inflammatory component to varying degrees. Arthritic entities of importance in horses include traumatic arthritis, osteochondritis dissecans, subchondral cystic lesions, septic (or infective) arthritis, and osteoarthritis (also called degenerative joint disease). Traumatic Arthritis Traumatic arthritis includes traumatic synovitis and capsulitis, intra-articular chip fractures, ligamentous tears (sprains) involving periarticular and intra-articular ligaments, meniscal tears, and osteoarthritis. Clinical Findings and Diagnosis: Traumatic synovitis and capsulitis is inflammation of the synovial membrane and fibrous joint capsule associated with trauma. Typically, the horse is an athlete and presents with synovial effusion in the acute stage, along with general thickening and fibrosis in the more chronic stage. Clinical signs of osteochondral fractures are similar to those of synovitis and capsulitis, as well as those of osteoarthritis; differential diagnosis of these entities is based on radiographs and, in some cases, arthroscopy. As a generalization, arthritis results in pain and altered function of the joint. If the process is active or acute, there is usually synovial effusion, and the surrounding tissues are swollen and warm. In more severe cases, manipulation of the joint causes pain. Treatment: Treatment of acute traumatic synovitis and capsulitis includes rest and physical therapy regimens such as cold water treatment, ice, passive flexion, and swimming. Nonsteroidal anti-inflammatory drugs (usually phenylbutazone) are used routinely. In more severe cases, lavage of the joint is done to remove inflammatory products produced by the synovial membrane, as well as articular cartilage debris that exacerbates the synovitis. Joint drainage alone, without lavage or injection of medication, provides only short-term relief. Various intra-articular medications have been used. Corticosteroids are the most potent anti-inflammatory agents and are effective in acute traumatic arthritis. However, there are differences in the side effects between various corticosteroids and various dosages. Betamethasone products and triamcinolone acetonide are effective with no deleterious side effects. Methylprednisolone acetate is more potent and longer acting than the other two drugs but excessive use could lead to degenerative changes in the articular cartilage. Intra-articular sodium hyaluronate has been used effectively for mild to moderate synovitis but has minimal effect on articular cartilage damage or when intraarticular fractures are present. Polysulfated glycosaminoglycans (PSGAG) are also used frequently for traumatic arthritis entities.
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Horses with osteochondral chip fragmentation (most commonly seen in the carpus and fetlock joints) are treated with arthroscopic surgery to minimize the ongoing development of osteoarthritis. Osteochondritis Dissecans Etiology and Epidemiology: The most common sites of osteochondritis dissecans (OCD), which usually occurs in young animals, are the femoropatellar joint, tibiotarsal (tarsocrural) joint, fetlock (metacarpophalangeal and metatarsophalangeal) joints, and the shoulder. See also Osteochondrosis: Introduction , Osteochondrosis , Osteochondrosis . Clinical Findings and Diagnosis: Animals with OCD of the shoulder usually present when <1 yr old with severe forelimb lameness and possibly some muscular atrophy. Animals with OCD in the other joints usually present with synovial effusion and varying degrees of lameness. Diagnosis is confirmed with radiographs. Treatment: The treatment of OCD depends on the location and degree of involvement. Subchondral Cystic Lesions Etiology and Epidemiology: Subchondral cystic lesions occur in the femorotibial joint and in the fetlock, pastern, elbow, shoulder, and distal phalanx. Treatment: Subchondral cystic lesions are most frequent in the femorotibial joint. Septic Arthritis (Infective arthritis) Etiology and Epidemiology: Septic or infective arthritis results from sequestration of bacterial infection in a joint. An infected joint develops in three main ways: 1) hematogenous infection, which is common in foals, calves, and lambs (commonly referred to as navel ill); 2) traumatic injury with local introduction of infection; 3) iatrogenic infection associated with joint injection or surgery (usually in horses). Navel ill is only one example of a hematogenous route of infection, which can also be gained from GI or pulmonary sources. Clinical Findings and Diagnosis: Septic arthritis is usually characterized by severe lameness and distention of the joint with cloudy, turbid synovial fluid that contains >30,000 WBC/mm3 and a total protein level of >4 g/dL. In foals, hematogenous osteomyelitis often accompanies septic arthritis. Septic arthritis in foals has been classified into type S (septic joint only), type P (involving osteomyelitis of the adjacent growth plate as well), or type E (involving osteomyelitis of the epiphyseal and subchondral bone). Control is best directed toward reducing the possibility of infection from the environment. Treatment: Septic arthritis requires prompt treatment to avoid irreparable damage. Osteoarthritis (Degenerative joint disease) Etiology and Epidemiology: Osteoarthritis represents the end stage of most of the other diseases discussed above if treatment is ineffective or the initial problem is too severe. The sine qua non of osteoarthritis is progressive degradation of articular cartilage—a permanent condition. Clinical Findings and Diagnosis: Lameness occurs and can be localized with analgesia to the affected joint. There will be varying degrees of synovial effusion, joint capsule fibrosis, and restricted motion (decreased flexion). Treatment: Treatment of osteoarthritis is most commonly palliative and includes the use of nonsteroidal anti-inflammatory drugs, polysulfated glycosaminoglycans, intra-articular corticosteroids, and IV hyaluronic acid. Physical therapy regimens are also gaining popularity. In advanced cases, surgical fusion (arthrodesis) may be performed on selected joints. Chlamydial Polyarthritis-serositis (Transmissible serositis) This infectious disease affects sheep, calves, goats, and pigs. Etiology and Epidemiology:

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Strains of the causal agent, Chlamydia psittaci , isolated from affected joints of sheep and calves are identical, but strain-specific antigens in their cell walls distinguish them from those that cause abortions in sheep and cattle ( Abortion In Large Animals: Introduction). The GI tract is of prime importance in the pathogenesis of chlamydial polyarthritis (see intestinal chlamydial infections, Intestinal Chlamydial Infections: Introduction). The ultimate site of replication is the synovial membrane. Chlamydiae are excreted in the feces and urine and transmitted via ingestion or, in some cases, inhalation. Clinical Findings: Chlamydial polyarthritis is seen in lambs on range, on farms, and in feedlots. Morbidity may be 5-75%. Rectal temperatures are 102-107°F (39-41.5°C). Varying degrees of stiffness, lameness, anorexia, and a concurrent conjunctivitis ( Chlamydial Conjunctivitis: Introduction) may occur. Affected sheep are depressed, reluctant to move, and often hesitate to stand and bear weight on one or more limbs, but they may “warm out” of stiffness and lameness after forced exercise. The highest incidence of the disease in sheep on range occurs between late summer and early winter. The disease affects cattle of all ages but calves 4-30 days old are affected more severely. Calves may have fever, are moderately alert, and usually nurse if carried to the dam and supported while sucking. They invariably also have diarrhea, which can be severe. Affected calves assume a hunched position while standing; their joints usually are swollen, and palpation causes pain. Navel involvement and nervous signs are not seen. Chlamydial polyarthritis has been recognized in older pigs as well as in young piglets. Lesions: The most striking tissue changes are in the joints. In lambs, enlargement of the joints is not often noticed, but in chronic advanced cases, the stifle, hock, and elbow may be slightly enlarged. Fibrin flakes and plaques in the recesses of the affected joints may adhere firmly to the synovial membranes. Diagnosis: Cytologic examination of synovial fluids or tissues may reveal chlamydial elementary bodies or cytoplasmic inclusions. Lambs with mineral deficiency or osteomalacia usually are not febrile. The abnormal osteogenesis in these two conditions and the distinct lesions of white muscle disease are virtually pathognomonic. In arthritis caused by Erysipelothrix rhusiopathiae , there are deposits on and pitting of articular surfaces, periarticular fibrosis, and osteophyte formation. Laminitis due to bluetongue virus infection can be differentiated clinically and etiologically. Detailed microbiologic investigations are required to differentiate chlamydial arthritis from mycoplasmal arthritis. Tendinitis (Bowed tendon) Inflammation of a tendon can be acute or chronic, with varying degrees of tendon fibril disruption. Tendinitis is most common in horses used at fast work, particularly racehorses. The problem occurs in the flexor tendons and is more common in the forelimb than in the hindlimb. Etiology: Tendinitis usually appears after fast exercise and is associated with overextension and poor conditioning, fatigue, poor racetrack conditions, and persistent training when inflammatory problems in the tendon already exist. Improper shoeing may also predispose to tendonitis. Poor conformation and poor training also have been implicated. Clinical Findings and Diagnosis: During the acute stage, the horse is severely lame and the involved structures are hot, painful, and swollen. In chronic cases, there is fibrosis with thickening and adhesions in the peritendinous area. The horse with chronic tendinitis may go sound while walking or trotting, but lameness may recur under hard work. Treatment: Tendinitis is best treated in the early, acute stage. The horse should be stall-rested, and the swelling and inflammation treated aggressively with cold packs and systemic anti-inflammatory agents. The horse should be brought back slowly into an exercise regimen to try to minimize the formation of adhesions. Superior check ligament desmotomy has been used more recently as an adjunctive treatment to minimize recurrence of the problem when the horse is returned to training. Splints (Interosseous desmitis) Splints primarily involve the interosseous ligament between the large (third) and small (second) metacarpal (less frequently the metatarsal) bones. The reaction is a periostitis with production of new bone (exostoses) along the involved splint bone. Trauma from concussion or injury, strain from excess training (especially in the immature horse), faulty conformation, or improper shoeing may be contributory factors. Splints most commonly involve the medial rudimentary metacarpal bones. Lameness is seen only when splints are forming and is seen most frequently in young horses. Lameness is more pronounced after the horse has been worked. In the
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early stages, there is no visible enlargement, but deep palpation may reveal local painful subperiosteal swelling. In the later stages, a calcified growth appears. After ossification, lameness disappears, except in rare cases in which the growth encroaches on the suspensory ligament or carpometacarpal articulation. Radiography is necessary to differentiate splints from fractured splint bones. If the exostoses impinge against the suspensory ligament, then surgical removal may be necessary. Congenital And Inherited Anomalies Of The Musculoskeletal System: Introduction Congenital disorders can be due to viral infections of the fetus or toxic plants ingested by the dam at certain stages of gestation. The musculoskeletal system can also be affected by certain congenital neurological disorders. See also congenital myopathies , Asymmetric Hindquarter Syndrome of Pigs. Angular Limb Deformities of Foals In these congenital or acquired skeletal defects, the distal portion of a limb deviates laterally or medially early in neonatal life. In utero malposition, hypothyroidism, trauma, poor conformation, excessive joint laxity, and defective endochondral ossification of the carpal or tarsal and long bones have been implicated. One to four limbs may be affected, depending on the severity of the condition. The carpus is affected most frequently, but the tarsus and fetlocks are occasionally involved. The deviation is obvious but varies in severity. A lateral deviation (valgus) of up to 6° of the distal portion of a limb may be regarded as normal. Most foals are asymptomatic, but lameness and soft-tissue swelling can accompany severe deviations. The distal radial metaphysis, physis, epiphysis, or cuboidal bones may be the site of deviation. Radiography is helpful in detecting physeal flaring, epiphyseal wedging, and deformation of carpal bones. Mildly affected foals frequently improve spontaneously without treatment. Excessive joint laxity, with or without cuboidal carpal bone involvement, requires tube casts or splints. The fetlock and phalangeal region should not be included in the casts, which should protect the weak joint from trauma but allow restricted exercise to maintain tendon and ligament tone. Such limb support may be required for up to 6 wk. Physeal and epiphyseal growth disturbances are also amenable to surgical correction through hemicircumferential transection and periosteal elevation of the distal radius on the concave side of the defect or through transphyseal bridging of the physis on the convex side. These surgeries must be performed before the physeal growth plates close (as early as 2-4 mo of age), and success depends on continued growth and development of the bones. Without treatment, the prognosis for severe carpal valgus is poor. Dyschondroplasia Dyschondroplasia of genetic origin occurs in most breeds of cattle. The forms range from the so-called Dexter “bulldog” lethal, in which the calf is invariably stillborn, to those animals that are mildly affected. Dyschondroplasia of the appendicular and axial skeletons also occurs in dogs. The former is reported in Poodles, and Scottish Terriers, the latter in Alaskan Malamutes, Basset Hounds, Dachshunds, Poodles and Scottish Terriers. In some breeds (Bassets, Dachshunds, Pekingese), the appendicular dyschondroplastic characters are an important feature of breed type. In Malamutes, the condition is accompanied by anemia. Interdigital Dermatitis (Stable footrot, Slurry heel, Scald) Interdigital dermatitis is a low-grade infection of the interdigital epidermis that causes a slow erosion of the skin with discomfort but no lameness unless the lesion becomes complicated. It is seen worldwide but is most prevalent under poor hygienic conditions in intensive dairy production. In tied systems, the hindlegs are more often affected than the forelegs. In loose housing systems, the distribution between fore and hindlegs is about equal. Animals on slatted floors are affected less often than animals on solid floors. Etiology and Pathogenesis: Interdigital dermatitis is caused by a mixed bacterial infection, but Dichelobacter nodosus has been considered to be the most active component. The disease is most commonly seen when the humidity is high, in temperate climates, and under poor hygienic conditions, especially in housed dairy cattle. The source of the infection is the cow itself, and the infection spreads from affected to nonaffected animals through the environment. Dichelobacter nodosus cannot survive >4 days on the ground but will persist in filth that is caked onto the claws. The bacteria invade the epidermis, but the organisms do not penetrate to the dermal layers. As the condition progresses, the border between the skin and soft heel horn disintegrates, producing lesions similar to ulcers or erosions. At this stage, the lesions causes discomfort. Clinical Findings:

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The first stage of the condition appears to be an exudative dermatitis. The exudate oozes to the commissures of the interdigital space and forms a crust or scab, which may be observed occasionally on the dorsal surface of the digits. As the condition progresses, the animal shows discomfort by “paddling,” ie, constantly moving from one foot to the other. If the heels of the hindfeet are especially painful, the limbs will be held further back than normal. True lameness does not occur until a complicating lesion is present. After a prolonged period, during which the animal has avoided bearing weight on the heel, the horn beneath the heel will increase in thickness and some aberrations of gait will result. Interdigital hyperplasia (corns, fibroma) may be caused by the chronic irritation of the interdigital space in dairy cows. Often, the fibroma will develop on one side of the interdigital space. The primary differential diagnosis is digital dermatitis (see Digital Dermatitis). The most obvious differences between the two diseases are the clinical signs and the highly contagious nature of digital dermatitis. Treatment: Systemic therapy, including antibiotics, is not effective. In severe cases, the lesions should be cleaned and dried, after which a topical bacteriostatic agent is applied, eg, a 50% mixture of sulfamethazine powder and anhydrous copper sulfate. Alternatively, an animal can be confined in a footbath for 1 hr b.i.d. for 3 days. Control: Good management and housing systems to keep claws dry and clean are most important. Digital Dermatitis Digital dermatitis is a highly contagious, erosive and proliferative infection of the epidermis proximal to the skin/horn junction in the flexor region of the interdigital space. The condition was first seen in European countries but, in recent years, it has spread across the dairyproducing areas of the USA. The incidence in beef cattle appears to be minimal. The incidence is highest in loosehoused herds that are not kept clean. The prevalence is highest in the fall and winter and is lowest if the animals are pastured. Etiology and Pathogenesis: Two main types of lesions occur, one is erosive/reactive, the other is proliferative or wart-like. Both forms cause varying degrees of discomfort and may give rise to severe lameness. The two forms likely represent different stages of the disease process. Some of the variation may be due to concurrent interdigital dermatitis (see Interdigital Dermatitis , Ovine Interdigital Dermatitis). Deep in the epidermis of erosive/reactive lesions, two types of spirochetes can be demonstrated using WarthinStarry stain. It is thought that there is a multifactorial etiology with multiple organisms being involved. Dichelobacter nodosus is likely to be implicated. Strong circumstantial evidence suggests that a virus plays a part in the pathogenesis of the disease, but to date, none has been isolated. Clinical Findings: Lesions are most common in the region of the flexor commissure of the interdigital space. Less typically, lesions have been seen on the dorsal surface of the foot as well as around the dewclaws. One or both hindfeet are most commonly involved, although both hind and forefeet can be affected. Small, early lesions are clearly separated from surrounding healthy skin by a white line of raised tissue. Typically, they are round or oval and ~0.5-2.0 cm in diameter. The surface of the lesion may be flat or concave, raw, moist, and red, yellow, or gray with a finely tufted or granular surface. The lesion is often referred to as being “strawberry-like.” Mature lesions are usually raised by as much as 2-4 cm, with the surface covered by gray, brown, or black hair-like papillary growths. The lesions are usually extremely tender to the touch. An affected animal may hold its foot off the ground or walk on its toes. Digital dermatitis is distinctly different in appearance from footrot because swelling and fever are normally absent. Treatment: In advanced cases, individual treatment may be necessary. The foot, especially the interdigital area, should be thoroughly cleansed to remove the prolific population of spirochetes. Some caustic preparations have been effective, eg, a single topical paint of 36% muriatic acid or formaldehyde. The dressing must be applied carefully to the infected tissue and protected by a waterproof bandage. A one-time treatment is likely to be effective, and repeated dressing with the caustic preparation is not advisable. Topical dressing of the lesion and surrounding surfaces with soluble oxytetracycline produces good results. Lincomycin-spectinomycin (66 g and 132 g/L of water, respectively) can be highly effective. Herd outbreaks are best treated with a footbath containing oxytetracycline or lincomycin-spectinomycin. Control: Digital dermatitis is exacerbated by filthy, wet conditions. Slurry removal and improved standards of hygiene are essential for control. In herds in which this condition is not yet a problem, animals should be isolated for 1 mo before being introduced into a herd. Vaccines are not available.
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Hyperkalemic Periodic Paralysis Hyperkalemic periodic paralysis (HPP) is a hereditary condition of Quarter horses that is the result of a genetic mutation in the skeletal muscle sodium channel gene. It is inherited as an autosomal dominant trait. Most affected horses are heterozygotes. The classic signs are muscle fasciculation, spasm, and weakness associated with hyperkalemia. However, these signs are only rarely observed in affected horses. Potential sequela of attacks are abrasions and involuntary recumbency. These problems are not specific for HPP but occur more frequently in affected horses. It is also likely that HPP results in greater muscle mass. There are suggestions that homozygotes may be more severely affected and show signs of upper respiratory obstruction as foals. The test of choice is the gene probe for the HPP type sodium channel DNA. This is the most sensitive test for detecting the mutation in horses susceptible to HPP. Diagnosis can also be based on the appearance of clinical signs, increased plasma potassium levels, and associated increased plasma potassium concentrations in response to oral potassium loading. All affected horses are descendants of the American Quarter horse sire Impressive. Enzootic Calcinosis This disease complex of ruminants and horses is caused by plant poisoning or mineral imbalances and characterized by extensive calcification of soft tissues. Etiology and Pathogenesis: Known causes fall into two categories: plant poisonings and mineral imbalances in the soil, the first probably being the more important. Cestrum diurnum (wild jasmine, day-blooming jessamine, king-of-the-day), Trisetum flavescens (golden oats or yellow oat grass), Nierembergia veitehii , Solanum esuriale , S torvum , and S malacoxylon (glaucophyllum) contain 1,25-dihydroxycholecalciferol (calcitriol) glycoside or a substance that mimics its calcinogenic action. Studies indicate that S malacoxylon has the required enzyme systems for the synthesis of calcitriol from vitamin D3. No concrete evidence incriminating other plants is available. The imbalance of minerals in certain soils in Hawaii, India, Austria, and possibly elsewhere has been thought to be the main etiologic factor; dietary mineral imbalance may contribute to the calcification chiefly associated with plant poisoning. Excessive phosphate or calcium, absolute or conditioned magnesium deficiency, and deficiency of potassium and nitrogen have all been incriminated or suspected. Osteodystrophy of bulls after prolonged intake of excessive calcium is a similar condition; calcification of the cardiovascular system associated with aging and such cachectic diseases as tuberculosis is not identical. Excessive vitamin D3 and normal or excessive calcium intake induces aortic calcification and atherosclerosis in ruminants. Normally, the conversion of 25-hydroxycholecalciferol (calcifediol) to calcitriol in the kidney is controlled by a feedback mechanism. The calcitriol-like factor in the leaves of plants bypasses this mechanism, and more calcium is absorbed than can be accommodated physiologically. Hypercalcemia promotes calcitonin production, calcinosis, and osteoporosis. Clinical Findings: The disease is progressive and chronic, extending over weeks or months. The earliest signs are stiffened and painful gait, which is most pronounced when the animal rises after prolonged rest. Forelimbs are particularly affected, and some animals even walk or graze on their knees. When standing, the forelimbs bow forward because the joints cannot be extended completely. The animal shifts weight to the forepart of the hooves or, alternatively, to each forelimb to ease stress on the carpus, which is thickened and painful. The distal joints become abnormally straight. When affected animals are forced to walk, their gait is awkward, stiff, and slow, and their steps are short. After walking only short distances, breathing becomes shallow and diaphragmatic, the nostrils are flared, and the head and neck are extended. Varying degrees of heart murmur are detectable, usually as a double or blurred second sound; these are exaggerated after exercise. Pulse rate is increased after slight exercise. Jugular pulse is prominent in some cases. Calcification of vessels is palpable on rectal examination. Lesions: Degeneration and calcification of soft tissues occur, with emaciation and varying amounts of excess fluid in the thoracic and abdominal cavities and pericardial sac. The cardiovascular system is the first to be involved, followed by lung, kidney, and tendons. The heart and aorta show the most marked effects. The left side of the heart is more affected than the right. Control: Removal of the causal factor(s) is essential, but when the disease is associated with the mineral content of the soil, control may be difficult. Change of pasture, forage, and environment may effect clinical improvement and even diminish the soft-tissue mineral deposits. Experimentally, daily administration of 15 g of aluminum hydroxide, PO, prevented the development of calcinosis in sheep fed Trisetum flavescens . Primary Hyperparathyroidism
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In primary hyperparathyroidism ( Primary Hyperparathyroidism), there is excess production of parathyroid hormone (PTH) by an autonomous functional lesion in the parathyroid gland. The normal control mechanisms for PTH secretion by the concentration of blood calcium are lost, and the parathyroid produces excess PTH despite increased levels of blood calcium. This disease is encountered infrequently in older dogs, and it does not appear to be a sequela of renal secondary hyperparathyroidism (see Renal Secondary Hyperparathyroidism). PTH acts on cells of the renal tubules initially to promote the excretion of phosphorus and retention of calcium. A prolonged increased secretion of PTH results in accelerated osteocytic and osteoclastic bone resorption. Mineral is removed from the skeleton and replaced by immature fibrous connective tissue. Fibrous osteodystrophy is generalized throughout the skeleton but is accentuated in local areas such as the cancellous bone of the skull. The increased PTH levels also inhibit the renal tubular resorption of phosphorus. The lesion in the parathyroid gland in dogs is usually an adenoma, occasionally a carcinoma, composed of active chief cells. Usually, adenomas are single, light brown-red, and located in the cervical region near the thyroid gland. Clinical Findings: Lameness follows severe osteoclastic bone resorption, and fractures of long bones occur after minor physical trauma. Compression fractures of weakened vertebral bodies may exert pressure on the spinal cord and nerves, resulting in motor and sensory dysfunction. Facial hyperostosis with partial obliteration of the nasal cavity (by poorly mineralized woven bone and highly vascular fibrous connective tissue) and loss or loosening of teeth has been seen in dogs. This may result in an inability to close the mouth properly and development of gingival ulcers. Bones of the skull are markedly thinned by the increased resorption and have a characteristic “moth-eaten” appearance radiographically. In advanced cases, the mandible can be twisted gently due to loss of osteoid and severe fibrous osteodystrophy—hence the name “rubber jaw” syndrome. Diagnosis: Although other laboratory findings may be variable, hypercalcemia is consistent and results from accelerated release of calcium from bone. The blood calcium in normal dogs is ~10 ± 1 mg/dL, depending on age and diet (and assay method). Serum calcium values consistently >12 mg/dL indicate hypercalcemia. Dogs with primary hyperparathyroidism usually have a serum calcium of ≥12-20 mg/dL. The blood phosphorus is low or in the low-normal range (≤4 mg/dL). The urinary excretion of phosphorus, and often of calcium, is increased and may result in nephrocalcinosis and urolithiasis. Accelerated bone matrix metabolism is reflected by increased urinary excretion of hydroxyproline. Serum alkaline phosphatase activity may be increased in animals with overt bone disease. Demonstration of increased levels of PTH by a species-specific assay in an adult to aged dog with hypercalcemia, hypophosphatemia, and evidence of generalized bone disease provides conclusive evidence of primary hyperparathyroidism. PTH can be measured by sensitive radioimmunoassays or immunoradiometric assays. Differential diagnoses include other causes of hypercalcemia, such as vitamin D intoxication (overdosage), enzootic calcinosis ( Enzootic Calcinosis), malignant neoplasms with osseous metastasis, and hypercalcemia of malignancy (see also Hypercalcemia of Malignancy). The hypercalcemia of hypervitaminosis D may be as high as that in primary hyperparathyroidism but is accompanied by varying degrees of hyperphosphatemia and normal serum alkaline phosphatase activity. Skeletal disease usually is absent, because the increased concentrations of blood calcium and phosphorus are derived principally from augmented intestinal absorption rather than bone resorption. Malignant neoplasms with osseous metastases may cause moderate hypercalcemia and hypercalciuria, but the alkaline phosphatase activity and serum phosphorus level usually are normal or only slightly increased. Osteolysis associated with tumor metastases results not only from a physical disruption of bone by proliferating neoplastic cells but also from local production of humoral substances that stimulate bone resorption, such as prostaglandins and interleukin-1. Primary parathyroid hyperplasia has been described in German Shepherd pups. Treatment: The objective is to eliminate the source of excessive PTH production. An attempt should be made to identify all four parathyroid glands before excising any tissue. Single or multiple adenomas should be removed in toto. If all identifiable parathyroids in the cervical region appear to be of normal or smaller size, and the diagnosis is reasonably certain, surgical exploration of the thorax near the base of the heart may be necessary to localize the parathyroid neoplasm. Removal of the functional parathyroid lesion results in a rapid decrease in circulating PTH levels because the halflife of PTH in plasma is <15 min. Because plasma calcium levels in animals with overt bone disease may decrease rapidly and be subnormal within 12-24 hr after surgery, they should be monitored frequently. If hypercalcemia persists for ≥1 wk after surgery, or recurs after initial improvement, a second adenoma or metastases from a carcinoma should be suspected. Renal Secondary Hyperparathyroidism Etiology and Pathogenesis: Renal secondary hyperparathyroidism is a complication of chronic renal failure characterized by increased endogenous levels of parathyroid hormone (PTH). It is more common than primary hyperparathyroidism. In contrast to primary hyperparathyroidism, renal secondary hyperparathyroidism tends not to be autonomous.
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With progressive renal disease, serum hyperphosphatemia occurs as the glomerular filtration rate decreases. Hyperphosphatemia leads to lower serum ionized calcium concentrations. Renal synthesis of calcitriol is also reduced. Calcitriol normally exhibits influence on the intestine and kidneys to maintain normal calcium levels. Decreased ionized calcium and calcitriol concentrations cause an increase in serum PTH concentrations. As glomerular filtration rate decreases with advancing renal disease, PTH concentrations progressively increase, leading to the clinical manifestations of renal secondary hyperparathyroidism. Clinical Findings: The predominant signs of renal insufficiency (eg, vomiting, dehydration, polydipsia, polyuria, and depression) are usually present. Skeletal lesions range from minor changes with early (or mild) renal disease to severe fibrous osteodystrophy of advanced renal failure. The volume of affected bones usually is normal (isostotic), particularly in older dogs because of the slow onset of renal failure and lower metabolic activity of bones. Hyperostotic bone lesions, such as facial swelling, may be seen in younger dogs in which deposition of unmineralized osteoid by hyperplastic osteoblasts and production of fibrous connective tissue exceed the rate of bone resorption. Resorption of alveolar bone occurs early and results in loose teeth, which may be dislodged easily and interfere with mastication. As a result of accelerated resorption of cancellous bone of the maxilla and mandible, bones become softened and pliable (“rubber jaw” syndrome), and the jaws fail to close properly. This often results in drooling and protrusion of the tongue. Severely demineralized mandibles are predisposed to fractures and displacement of teeth from alveoli. Long bones are less dramatically affected. Lameness, stiff gait, and fractures after minor trauma may result from increased bone resorption. Lesions: All parathyroid glands are enlarged, initially due to hypertrophy of chief cells and subsequently by compensatory hyperplasia. Although the parathyroids are not autonomous, the concentration of PTH in the peripheral blood often exceeds that of primary hyperparathyroidism. Changes such as osteoclastosis, marrow fibrosis, and a higher concentration of woven osteoid may be seen histologically. Severe hypercalcemia, hyperphosphatemia, and high concentrations of PTH present in advanced disease may cause osteosclerosis. Diagnosis: Renal secondary hyperparathyroidism is diagnosed by laboratory abnormalities consistent with renal insufficiency accompanied by an increase in serum PTH. Treatment: Treatment options include dietary modification, calcitriol supplementation, and phosphate binders, as well as management of the underlying renal disease. Oral calcitriol (1.5-3.5 ng/kg/day) has reversed hyperparathyroidism of chronic renal failure, but calcitriol therapy is contraindicated with hyperphosphatemia or hypercalcemia. Dietary phosphorus binders are used to decrease the amount of phosphorus absorbed in the intestines and should be administered with meals. This therapy is especially important during calcitriol supplementation because calcitriol will increase the absorption of phosphorus as well as calcium. Hypoparathyroidism In hypoparathyroidism ( Hypoparathyroidism), either subnormal amounts of parathyroid hormone (PTH) are secreted, or the hormone secreted is unable to interact normally with target cells. It has been recognized primarily in dogs, particularly in smaller breeds such as Miniature Schnauzers, but other breeds may be affected. Etiology and Pathogenesis: Various pathogenic mechanisms can result in inadequate secretion of PTH. Parathyroid glands may be damaged or inadvertently removed during thyroid surgery. Idiopathic hypoparathyroidism in adult dogs usually is the result of diffuse lymphocytic parathyroiditis that causes extensive degeneration of chief cells and replacement by fibrous connective tissue. Other possible causes of hypoparathyroidism include destruction of parathyroids by primary or metastatic neoplasms in the anterior cervical area, and atrophy of parathyroids associated with chronic hypercalcemia. The presence of numerous distemper virus particles in chief cells of the parathyroid gland may contribute to the low blood calcium in certain dogs with this disease. An immunemediated mechanism may be involved, because a similar destruction of secretory parenchyma and lymphocytic infiltration has been produced experimentally in dogs by repeated injections of parathyroid tissue emulsions. Clinical Findings and Lesions: The functional disturbances and clinical manifestations of hypoparathyroidism primarily are the result of increased neuromuscular excitability and tetany. Bone resorption is decreased because of the lack of PTH, and blood calcium levels diminish progressively (4-6 mg/dL). Affected dogs are restless, nervous, and ataxic, with weakness and intermittent tremors of individual muscle groups that progress to generalized tetany and convulsions. Blood phosphorus levels are increased substantially, owing to increased renal tubular reabsorption. Calcification of microvasculature, intracerebral calcification, decreased mental function, cataracts, osteopenia, and ligamentous ossification have been associated with chronic hypoparathyroidism.
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In the early stages of immune-mediated lymphocytic parathyroiditis in dogs, there is infiltration of the gland with lymphocytes and plasma cells and nodular regenerative hyperplasia of remaining chief cells. Later, the parathyroid gland is replaced by lymphocytes, fibroblasts, and capillaries, with only an occasional viable chief cell. Diagnosis: This is based on clinical signs of increased neuromuscular excitability, severe hypocalcemia, and often moderate hyperphosphatemia in a nonparturient animal, as well as on the response to therapy. Some of the signs (eg, tetany) and laboratory data (eg, hypocalcemia) are similar to those of puerperal hypocalcemia ( Puerperal Hypocalcemia In Small Animals: Introduction). However, puerperal hypocalcemia usually is accompanied by hypophosphatemia and a low-normal or subnormal blood glucose concentration as a result of the associated intense muscular activity. Treatment: The neuromuscular tetany should be treated initially by restoring blood calcium levels to near normal by IV administration of calcium gluconate. Care must be given to not administer the calcium too rapidly due to its cardiotoxic properties. Long-term maintenance of blood calcium levels in the absence of normal PTH secretion should be attempted by feeding diets that are high in calcium and low in phosphorus and that are supplemented with calcium (gluconate or lactate) and vitamin D3 . Large doses of vitamin D3 (≥25,000-50,000 u/day, depending on the size of the dog) may be required initially to increase the blood calcium level in hypoparathyroid animals because the lack of PTH diminishes the rate of formation of the biologically active vitamin D metabolite in the kidney. Once the blood calcium has returned to normal, substantially lower doses of vitamin D are indicated for long-term maintenance; in some dogs, only dietary calcium supplementation is required for long-term stabilization. Lameness, General Principles: Introduction Lameness is not a disease but an indication of pain, weakness, deformity, or other impediment in the musculoskeletal system. Lameness can be classified into weight bearing (supporting-leg) and nonweight-bearing (swinging-leg) disorders. A supporting-leg lameness is seen when the animal reduces the extent and duration of weight bearing by taking a shorter step and elevating the body during the support phase of the stride. This occurs particularly with injuries to the feet, bones, tendons, ligaments, and motor nerves. A swinging-leg lameness is seen during the swing phase of the stride cycle when the limb is being brought forward and often involves lesions in the joint. Etiology and Predisposing Factors Causes of lameness may be classified as predisposing or exciting. Predisposing causes involve immaturity or poor condition, faulty conformation, systemic disease, lack of attention to the feet, or in horses, bad shoeing. Exciting causes involve direct or indirect trauma; incoordination of muscle action, as may occur in tired animals; and inflammation with or without infection, especially of the feet, tendon sheaths, and joints. Terms such as shoulder lameness, hip lameness, and tarsal lameness are often used to describe so-called regional lameness. In large animals, except for Standardbred horses, most lamenesses affect the forelimbs, usually from the carpus distally. In small animals, trauma is probably the single most important factor in causing lameness. In farm animals, nutrition and the environment (ie, climate, housing, herd size, hygiene) are all important. Signalment and History: In today's light horses, most cases of forelimb lameness arise from the fetlock distally. Forelimb Lameness: The head is raised when the lame limb bears weight and is dropped when the unaffected limb is in support. In the horse, the sound made by each hoof as it strikes the ground may also indicate the lame limb. Hindlimb Lameness: The croup on the affected side is generally raised when the lame limb is in support; the degree of elevation of the croup varies with the source and severity of lameness. When both hindlimbs are lame, the gait is stiff and restricted, similar to that seen with back problems. When the lame leg has been identified, the following should be assessed: degree of flexion of the joints, length of stride, adduction or abduction of the limb, placement of the foot, and height to which the hocks are carried. Lameness In Cattle: Introduction The Lameness Examination Visual Appearance of the Standing Animal:

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Normal stance is assumed when weight is distributed normally between the digits. More weight is borne by the forelimbs than by the hindlimbs, and each of the four fore or hind claws bear weight equally. The point of the hock normally lies directly beneath the pin bone when viewed either from the side or from behind. In lameness, an animal will assume a different stance or posture because of some abnormal influence or to relieve pain. A painful abscess in a lateral hind claw will cause the animal to abduct that limb. If the horn of the sole beneath the heel of a lateral claw increases in thickness (overburdened), the animal will assume a “cow hocked” posture. Some abnormal postures can be confused with abnormal conformation. An animal is said to be “camped forward” when the limb is protracted forward more than is normal. This posture is associated with pain in the apex (toe) of the claw. In the hindlimb, this can be confused with “sickle hock,” a conformation in which the angle of the hock is <160°. By contrast, when there is pain in the heel region, the limb is retracted or held further back than is normal, and the animal is said to be standing “camped back.” This posture may be confused with “post leg,” a confirmation in which the angle of the hock is >180°. Another common posture is adduction, particularly of the hindlimbs. When the hind feet are held closer together than normal because there is pain in the medial claw, the animal is said to be “standing narrow.” This posture is often confused with the conformation called “bow leg.” An abducted posture usually indicates that pain is present in the lateral claw. Radiography of the Digital Region: The cause of over 90% of lameness is located in the digital region. In the dorsopalmar/plantar projection, the image produced shows all of the major bones and joints without overlap. This is an extremely useful view from which many diseases of the bovine foot can be correctly diagnosed. Ultrasonography: Ultrasonography can be used to evaluate injuries to the tendons and ligaments, and it may prove of value in identifying radiolucent foreign bodies and tracing sinus tracts and deep abscesses, particularly within large muscle masses. Electromyography: Electromyography (EMG) can be used to detect failure in the nerve supply to muscles. Regional Analgesia Intravenous regional analgesia is the method of choice of analgesia for most digital surgical procedures. Arthroscopy and Arthrocentesis Joint Entry Sites Arthroscopy enables the operator to visualize the interior surfaces of a joint for diagnostic or surgical purposes. Arthrocentesis is a procedure by which synovial fluid may be removed from a joint for examination. Joint Entry Sites: For the distal interphalangeal joint (coffin joint), the needle is inserted lateral to the common or long extensor tendon, which inserts into the extensor process of the distal phalanx. The entry point is just proximal to the coronary band. For the pastern joint (proximal interphalangeal joint), the needle is inserted lateral to the extensor tendon. For the fetlock joint (metacarpophalangeal or metatarsophalangeal joint), the needle is directed downward close to the bone and between it and the interosseous (suspensory) ligament. Because this procedure may be painful, a nerve block at a higher level is recommended. The joint can also be entered from the dorsal surface in a similar manner to the distal joints; however, the flexor pouch is more capacious than the dorsal one. For the digital synovial sheath (sheath of the deep flexor tendon), the needle is directed downward behind the interosseous ligament. For the stifle joint, it is advisable to use two sites because the lateral femorotibial compartment in some animals may not communicate with the rest of the joint. The first site is close behind the lateral patellar ligament (lateral femorotibial compartment); the needle should be directed caudally. The needle is inserted in the second site between the medial and middle patellar ligaments and directed slightly down and toward the large medial lip of the trochlea (femoropatellar and medial femorotibial compartments). For the hip joint, the needle should be directed caudally and medially in front of the trochanter major and just in front of the insertion of the middle gluteus. Functional Claw Trimming Horn that is dry tends to be extremely resistant to wear and may grow longer than normal. Similarly, the claws of cattle maintained in straw yards tend to become overgrown. The claws of cattle maintained in extremely wet conditions are softer than normal and more prone to wear if the animals are housed on concrete surfaces. However, there is a tendency for wear to be irregular on abrasive concrete surfaces.
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When claws are correctly trimmed at least once each year, longevity of the herd may be extended by 1 yr. However, unskilled claw trimming has a negative effect on the claw health of a herd. When cows walk on concrete, the lateral claw tends to slip and grow faster than it wears. Thus, when standing, the overburdened lateral claw bears much more weight than the medial claw. The angle between the wall and the ground surface should be >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 <13°C. The stronger the formalin solution used, the more effective it will be, but the danger of a chemical burn on the cow's skin will also be greater. Therefore, the status of the hair around the claw should be carefully monitored. If the hair appears to be standing on end or the skin is pink, treatment should be suspended. Disorders Of The Claw And Interdigital Space: Overview Over 90% of claw lameness involves the hind digits, with the lateral claw implicated most frequently. The interdigital space and digital skin are the sites for a number of important infectious diseases, including interdigital phlegmon (footrot), interdigital dermatitis, digital dermatitis, foot-and-mouth disease, etc. Foreign Bodies in the Sole Occasionally, a foreign body, such as a stone, chip of glass, or nail, will become embedded in the sole. Even if the material does not penetrate to the corium, localized pressure will cause pain and lameness. Removal of the foreign body usually resolves the lameness without incident. If the foreign body penetrates through to the corium, infection will be introduced and an abscess will develop, leading to septic pododermatitis. Treatment consists of removing the foreign body and coring out the track to the corium with the fine-pointed hoof knife. Creating a large hole is inappropriate. Pus is often released under considerable pressure. Antibiotic should be squeezed into the cavity, which will close rapidly. The opening should not be plugged but covered lightly for a few days to prevent blockage with mud or manure. Pododermatitis Circumscripta (Sole Ulcer) A sole ulcer is a lesion located in the region of the sole/bulb junction, usually nearer the axial than abaxial margin. Damage to the dermis is associated with a circumscribed zone of localized hemorrhage and necrosis. Sole ulcers are common in dairy herds in which animals are managed in loosehousing systems, particularly if conditions are unhygienic as is often the case during winter months. The incidence is variable, but in some herds, >50% of the mature cows can be affected. Etiology and Pathogenesis: It is widely thought that subclinical laminitis is a major predisposing factor. Laminitis damages horn-producing tissues, resulting in softer than normal sole horn. The horn is further softened if it is exposed to moisture, while the chemical agents in slurry are thought to disrupt the integrity of the horn. Excess wear of the softened sole horn flattens and thins the sole. Weight bearing beneath the flexor process of the distal phalanx causes the sole to squeeze the corium in the region and leads to an ischemic necrosis occurring over a small area. Horn production ceases in this specific area, and as the surrounding horn continues to grow, the damaged area continues to persist as a perforation. The damaged corium undergoes repair until the granulation tissues erupts through the sole. Clinical Findings: Because the lateral digit is usually involved, the limb is often held slightly abducted with weight bearing on the unaffected medial digit.
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Grossly, the lesion varies from a soft, slightly discolored area that may be painful under pressure to an obvious circumscribed perforation. This is often the stage at which the lameness becomes severe enough to be noticed. In later stages, granulation tissue protrudes through the sole defect. Infection of the exposed corium may cause varying degrees of separation of the sole. Once the corium is exposed, infection can invade the deeper structures of the claw and spread proximally to involve the navicular bursa, resulting in necrosis of the flexor tendon and ligaments of the navicular bone. Rupture of the flexor tendon leads to dorsal rotation (upward) of the toe (“cocked toe”). In complicated cases, infection may progress up the deep flexor tendon sheath. Paring the surrounding horn may reveal hemorrhagic staining, which indicates that subclinical laminitis is associated with the etiology. Treatment: Treatment must be aimed at removing pressure from the affected area. Therapeutic claw trimming, if done skillfully, is highly effective. This procedure lowers the entire bearing surface of the lateral claw, which transfers weight bearing to the sound medial claw. Fixing a wooden or rubber block to the unaffected medial claw removes all weight bearing from the ulcer region and is an ideal treatment. Claw blocks should be kept on for a maximum of 6 wk. Protruding granulation tissue should not be excised or treated with any caustic agent because this can retard healing. Bandages should not be applied because this will result in continued weight bearing at the ulcer site; furthermore, covering the lesion will cause it to remain moist and promote maceration and bacterial infection. Prevention and Control: Because the occurrence of sole ulcers is believed to be intimately related to subclinical laminitis, the latter should be investigated and appropriate control measures instituted. White Line Disease White line disease is characterized by the separation (avulsion) of the fibrous junction between the sole and wall on the abaxial border of the sole. The corium becomes infected through this opening, and tracks of infection may localize as an abscess or penetrate deeper to form a retroarticular abscess. White line disease is a major cause of lameness, particularly when cattle are housed and fed concentrates. The incidence in multiparous cows can be as high as 35%. Etiology and Pathogenesis: The white line is as deep as the contiguous sole and is the softest part of the horn capsule. Rupture of the white line is exacerbated by the impact of locomotion, particularly among animals housed on concrete. It should be emphasized that the abaxial region of the wall of the hindlimb is the area of the claw that absorbs concussion first and in which horn growth and wear is maximal. Solid foreign bodies may lodge in the softened, widened zone. They may push through to the corium beneath and introduce infection; however, the presence of a foreign body is not essential for the lesion to occur. Tracks forming closer to the heel are likely to cause infection of the bursa of the deep flexor tendon. Invariably, the bursa will rupture into the retroarticular space, and an abscess will develop in this location. Infection of the distal interphalangeal joint and the tendon sheath of the deep flexor tendon may follow. Necrosis and avulsion of the insertion of the deep flexor tendon into the distal phalanx is a frequent complication. When this condition is associated with subclinical laminitis, the first indication may be hemorrhage into the white line. Clinical Findings: The lateral claw of the hindfoot (often both) is usually involved. If bilateral, the disease may remain unnoticed until lameness is more pronounced in one limb than the other. Discharge of pus from the skin/horn junction above the abaxial wall is always reason to suspect a white line lesion. In these cases, the white line must always be examined very carefully. Swelling of the heel bulb, represents the most advanced form of this condition; it is frequently misdiagnosed as footrot (often presented as a case of footrot that is resistant to treatment). Footrot causes the foot to swell evenly to the fetlock but, in contrast, a retroarticular abscess leads to enlargement of only one heel bulb. When infection (and necrosis) of the deep flexor tendon occurs, it usually avulses, and the toe of the affected digit will hyperextend with each step and eventually ankylose in a cocked-up position. Treatment: Abscessation with sinus formation at the coronary band requires the removal of a segment of the abaxial wall (~0.75 cm wide) from the white line to the coronary band. This procedure can be performed with the cutting disc of a grinding tool, but it can be painful and local anesthesia may be required. Often, a plug of necrotic debris is found in the track. For retroarticular abscesses, which are usually quite large and surrounded by a mass of fibroelastic tissue that inhibits drainage, drainage is accomplished by entering the abscess through the middle of the abaxial wall. Toe Ulcer

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A toe ulcer is a hemorrhage or separation of the white line in the toe region. The incidence is sporadic. It may be associated with subclinical laminitis. Etiology and Pathogenesis: This phenomenon probably results from congestion of the circumferential artery in the toe region after sudden introduction to high-energy feed. Clinical Findings: In many cases, the white line in the toe region may be stained with serum or blood. Treatment and Control: There are no reports of treatment; however, it seems rational to provide protection with a methyl methacrylate covering. Control of subclinical laminitis is likely to ameliorate this condition. If perforation at the toe has occurred, the long-term prognosis is poor. However, if treatment is attempted, aggressive systemic antibiotic therapy should be instituted immediately. The lesion should be packed with a hygroscopic mixture (50% magnesium sulfate and 50% glycerine) and left bandaged for a maximum of 24 hr. Double Sole In a double sole, a superficial sole is separated by a space from a second sole that is attached directly to the dermis. Etiology and Pathogenesis: A double sole may result from a short-term nutritional insult. A sudden disturbance in the microcirculation of the dermis probably results in an effusion of serum that separates the dermis from the epidermis. The condition has been seen in animals suddenly changed from a mainly forage diet to one rich in concentrates and in beef cattle turned out in the spring on lush grass after a winter ration of forage. The etiology is similar to that causing toe ulcer or digit rotation. Treatment and Control: The sole beneath is extremely soft and vulnerable to damage; therefore, the animal should be confined to a wellstrawed loose stall until the new horn has hardened, after which more of the sole may be removed. For control, sudden changes from forage to concentrate or lush grass should be avoided. Vertical Fissures (Sandcrack) A vertical fissure is a crack in the wall of the claw that has been classified into four types: Type I is confined to the coronary band, Type II is from the coronary band to the middle of the claw, Type III is from the coronary band to the bearing surface of the wall, and Type IV is from the middle of the wall to the bearing surface. Etiology: The etiology remains uncertain. Most fissures occur in the front outside claw. Heavy cows and animals with overgrown claws are more likely to be affected. Traumatic injury of the coronary band is likely to be the main cause of type I fissures. Many type II and III fissures are associated with horizontal fissures. The horizontal fissure is a point of structural weakness at which the claw will bend once the fissure has grown out to a point halfway between the coronary band and the apex of the toe. The stability of the wall is compromised, and vertical fissures apparently result from mechanical stress. Type IV fissures are quite rare and probably represent the resolving stages of type II and III fissures. Treatment: Most sandcracks are not painful and require no treatment. Type I fissures are only dangerous if they are located in the region where dorsal and abaxial surfaces meet. At this location, the dorsal pouch of the distal interphalangeal joint lies immediately beneath the coronary band. If such a fissure is infected, the risk of a septic joint is considerable. In these cases, a small segment of horn should be dissected from either side of the fissure, and the cavity dressed with antibiotic powder. Type II and III fissures often have ragged edges that may be twisted and gape open. Horizontal Fissures Horizontal fissures result from disruption of horn production at the dermis beneath the coronary band, which results in a defect in the integrity of the wall running parallel to the coronary band. The defect varies in severity from a shallow groove (hardship groove) to a complete fracture (fissure) of the wall. The fissure moves distally as the claw grows, and the distal portion becomes progressively more mobile (thimble) until it fractures, leaving a “broken toe.” A series of grooves can destabilize the vertical strength of the dorsal wall causing it to bend (buckled toe). Etiology:

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It is believed that fissures can be caused by a wide variety of stressors, including an acute febrile disease or a sudden, relatively short-term but significant change in nutrition (see also laminitis, Laminitis: Overview , Laminitis , Laminitis , Septic Laminitis). Clinical Findings: The horizontal groove or fissure is an important indicator of metabolic disturbance. The date on which the causal insult occurred can be calculated by measuring the distance from the distal edge of the coronary band to the fissure and dividing that number by the growth rate of the claw. In dairy cows, the rate of growth of the wall measured at the abaxial groove (part of the wall just in front of the heel bulb), is 0.5-0.6 cm/mo. In beef cows, the rate of growth measured along the dorsal flexure of the claw surface is 0.2-0.3 cm/mo. Growth rate appears to vary with age, plane of nutrition, and season of the year. Treatment: Most cases require no treatment. Heel Erosion Heel erosion is an aberration in the appearance of the surface of the bulb of the heel. The incidence of heel horn erosion (“slurry heel”) is most common during the winter, particularly when the claws are exposed to an unhygienic, moist environment (such as exists in intensively managed dairy units). Because heel erosion does not cause lameness per se, the true incidence is unknown. Etiology and Pathogenesis: During the destructive phase, heel erosion occurs most frequently when interdigital dermatitis is present, and Dichelobacter nodosus is likely involved. Claws exposed to slurry appear to have a higher incidence of erosions than those that are kept clean and dry. Moisture undoubtedly softens horn, and slurry contains a huge bacterial burden as well as an undetermined number of irritants. In the secondary phase, it is thought that changes in the distribution of weight bearing occur as the result of heel horn loss. This in turn causes an increase in the rate of horn produced beneath the heel. The excessive horn growth is often more pronounced in the lateral claw and causes the hock to turn in (cow-hocked stance). Interdigital Phlegmon (Footrot, Foul in the foot) Footrot is a subacute or acute necrotic infection originating from a lesion in the interdigital skin that leads to a cellulitis in the digital region. Pain, severe lameness, fever, anorexia, loss of condition, and reduced milk production are major signs of the disease. Etiology and Pathogenesis: Injury to the interdigital skin provides a portal of entry for infection. Maceration of the skin by water, feces, and urine may predispose to injuries. Fusobacterium necrophorum is considered to be the major cause of interdigital phlegmon. It can be isolated from feces, which may explain why control is difficult. Other organisms, such as Staphylococcus aureus , Escherichia coli , Actinomyces pyogenes , and possibly Bacteroides melaninogenicus , can also be involved. Clinical Findings: Both the fore or, more commonly, the hind digits can be affected, but it is rare that more than one foot is affected at the same time in dairy cows. However, the disease can occasionally occur in several feet in calves. The first sign is swelling and erythema of the soft tissues of the interdigital space and the adjacent coronary band. The inflammation may extend to the pastern and fetlock. Typically the claws are markedly separated, and the inflammatory edema is uniformly distributed between the two digits. The onset of the disease is rapid, and the extreme pain leads to increasing lameness. In severe cases, the animal is reluctant to bear weight on the affected foot. The body temperature is increased and appetite is reduced. The skin of the interdigital space first appears discolored; later, it fragments with exudate production. As necrosis of the skin progresses, sloughing of tissue is likely to follow. A characteristic foul odor is produced. If the disease proceeds unchecked, there will be severe weight loss and a significant reduction in milk yield. Milk production may not recover during the current lactation. Open lesions can be infected with secondary invaders. If the necrotic lesion is located in the anterior region of the interdigital space, the distal interphalangeal joint can become infected because of its proximity. Hematogenous infection of the tissues of the interdigital space may account for peracute cases of interdigital phlegmon, which are referred to as either “blind” or “super foul.” This form of the disease is characterized by the initial absence of a skin lesion, extreme pain, and the tendency to progress despite aggressive therapy. Diagnosis:

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Although it is easy to assume that every cow with a swollen foot is affected with interdigital phlegmon, many other conditions (eg, infected sandcracks, white line disease, retroarticular abscesses, foreign bodies in the interdigital space, and infection of the distal interphalangeal joint) can have the same appearance as footrot if viewed from a distance. Despite the difficulties encountered in lifting a hindlimb, a detailed examination should be performed in every case. An incorrect diagnosis can have disastrous results. Treatment: Treatment of “super foul” must be particularly aggressive. Early cases respond well to single doses of long-acting oxytetracycline. Local treatment is essential for some long-standing cases and in all instances in which the anterior region of the interdigital space has been compromised. The animal must be adequately restrained, and the lesion cleansed and necrotic tissue removed. A nonirritant bacteriostatic agent (such as nitrofurazone or a sulfa preparation) should be applied as a topical dressing. The application of gauze, cotton batting, or bandage is contraindicated. However, the lesion can be protected and immobilized by binding the digits together with a bandage. The entire digital region can be protected from contamination if it is enclosed in a plastic bag that is fixed in place with an adhesive bandage. However, prolonged protection is not advocated because the enclosed lesion tends to macerate further. Bandages, if used, should be replaced daily. Prevention and Control: Animals that are actively shedding infectious organisms should be isolated until signs of lameness have disappeared. Vaccines against F necrophorum have failed because of the weak immune response to the bacterium. High levels of zinc fed as a supplement may have a beneficial effect by improving epidermal resistance to bacterial invaders. Laminitis: Overview Laminitis is a pathophysiologic disturbance of the microvasculature of the corium that compromises the function of the tissues, particularly those of the horn-producing cells. Laminitis can be subclinical, acute, or chronic, depending on the severity of the several causative variables. Subclinical Laminitis This form of laminitis has the greatest economic importance; it produces no immediately obvious clinical signs but is suspected to be present in a herd if there is a high incidence of diseases such as sole ulcer. Subclinical laminitis has been reported mostly in mature dairy cows. Etiology: The classic hypothesis for the etiology of laminitis in cattle is similar to that of laminitis in horses ( Laminitis: Overview , Laminitis , Laminitis , Septic Laminitis). High levels of carbohydrate in the rumen invoke an increase of Streptococcus bovis and Lactobacillus spp , which in turn lead to a state of acidosis in the rumen. It is further hypothesized that this environment is hostile to gram-negative organisms and, as they die, vasoactive endotoxins are released. Rumenitis is frequently associated with ruminal acidosis. High levels of histamine in the blood have been found in the early stages of the disease. Fiber and the frequency of feeding are extremely important factors. A second hypothesis involves the receptors for epidermal growth factor (EGF) that are present in the corium of the claw. Because EGF is liberated in large quantities from the GI tract that has been insulted, it could be involved in the pathogenesis of laminitis. In addition to its mitogenic effect, EGF can inhibit the differentiation of keratinocytes in vitro. Inhibited differentiation of keratinocytes of the hoof matrix is a dominant morphologic feature in the early stages of laminitis. This hypothesis might account for the irregularities in horn production that are seen in some cases of laminitis. Pathogenesis: The pathophysiologic process causing laminitis may be summarized as a toxic influence on capillary walls that results in insufficient nutrient supply to the keratin-producing cells and synthesis of structurally incompetent keratin. It is believed that when vasoactive toxins reach the corium, the arteriovenous shunts are paralyzed. Pressure inside the claw rises, and the vessels are damaged, which allows blood or blood fluids to escape and soak into the horn claw staining it either pink or yellow. Hemorrhagic staining of the horn tubules of the sole give a “brush mark” appearance. Increased blood pressure inside the claw (intraungular pressure) and the associated reduced blood flow, is usually followed by thrombus formation. This is a characteristic feature of laminitis. Thrombi form as fine layers inside the walls (mural thrombi) of the vessels. Because of reduced blood flow, fewer nutrients reach horn-producing tissues, and horn quality deteriorates. The blood vessels can eventually become completely blocked, causing ischemic changes followed by scar tissue formation. Frequently, young animals appear to recover from a laminitic incident. This may be because new blood vessels develop to form collateral circulation and take over the function of those that have been damaged. Nevertheless, each time an animal has a bout of laminitis, more scar tissue is formed and the animal will be less able to recover from the next insult. Clinical Findings: Some animals appear to walk in a deliberate, careful manner, with a delayed appearance of hemorrhages in the sole. Erythema and edema of the coronary band above the heel and around the dewclaws in freshly calved cows may be an
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indication that a transitory laminitis-like insult is occurring. An annual herd incidence of 10% is probably an indication that the animals are being introduced to concentrate too rapidly. The best evidence of subclinical laminitis is the presence of sole ulcers and white line disease. Treatment and Control: Treatment for subclinical laminitis is impractical because diagnosis in an individual animal is not possible at the time of the causative insult(s). Acute or Subacute Laminitis Acute laminitis is not common in cattle and usually occurs in a single animal or a group that has accidentally engorged on large quantities of grain. Treatment: Antihistamines may be useful if given within the first 48 hr after a known insult. Anti-inflammatory drugs may be useful if given before the onset of acute signs. However, caution should be exercised in using corticosteroids later than 24 hr after signs appear. Control: Because acute laminitis usually develops as the result of an accident, little can be done to prevent the condition. Chronic Laminitis Chronic laminitis is assumed to be caused by a series of laminitic insults. It is seen most commonly in dairy cows >5 yr old. Lameness In Sheep: Introduction Lameness in sheep may be caused by a number of systemic diseases. The more common conditions, listed by age group usually affected, are as follows: lambs—joint-ill, tetanus, white muscle disease, enzootic ataxia (copper deficiency), polyarthritis (chlamydial), rickets, poisonous plant intoxication (eg, sneezeweed), and contagious ecthyma (orf); adults— mastitis, epididymitis, and mineral and trace element imbalances; any age—erysipelas (one of the more important, Erysipelas: Introduction , Swine Erysipelas), laminitis, bluetongue, ulcerative dermatosis, foot-and-mouth disease, and dermatophilosis. Many lamenesses are due to injuries. In addition to systemic diseases and injuries, lameness can be caused by a group of infections specific to the feet. These are mixed infections with combinations of bacteria, including Fusobacterium necrophorum . The skin between the claws is the primary site of invasion, but this usually does not occur when the stratum corneum is dry and intact. Predisposing causes are damage by water, maceration, frostbite, or mechanical trauma. Epidermal penetration by F necrophorum and Actinomyces pyogenes induces a transient condition, ovine interdigital dermatitis; when there is concurrent invasion by Dichelobacter nodosus , footrot results. This may be benign or virulent, depending on the strain of D nodosus . When the dermal and subdermal invasion by F necrophorum and A pyogenes involves the distal interphalangeal joint, foot abscess develops. Infection of the hoof matrix with these organisms results in septic laminitis. These five distinct but related conditions are discussed below. Foot Abscess (Infective bulbar necrosis, Heel abscess, Bumblefoot) A foot abscess is a necrotizing or purulent infection involving the distal interphalangeal joint. The incidence is usually sporadic, but up to 15% of rams or ewes in late pregnancy may be affected. The two organisms most consistently recovered from foot abscess are Fusobacterium necrophorum and Actinomyces pyogenes . Most commonly, foot abscess develops as a complication of ovine interdigital dermatitis (see Ovine Interdigital Dermatitis) by extension of the necrotic process into the subcutis and then into the distal interphalangeal joint. This joint is vulnerable to infection on the interdigital aspect where the joint capsule protrudes above the coronary border as the dorsal and volar pouches. At these two sites, the joint capsule is protected only by the interdigital skin and a minimal amount of subcutaneous tissue. Sporadic cases may also develop after penetration by sharp objects or careless paring of the hoof. Foot abscess develops most often when the soil and pastures are wet. Rams, particularly in their first winter, and ewes during late pregnancy are affected most commonly. The disease causes an acute lameness that is usually restricted to one foot. In the early stages, it may be possible to express necrotic material through an opening in the interdigital skin via the channel caused by the bacterial invasion. In ~50% of the cases, movement of the affected digit is exaggerated, which indicates that the ligaments about the distal interphalangeal joint have ruptured; it is likely that there will be displacement of the digit during locomotion, and permanent deformity. Acute lameness, swelling of one digit, and discharging sinuses distinguish foot abscess from footrot.

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Once the infection becomes established in the joint, treatment is of limited value. Therapy should be aimed at maintaining the integrity of the joint ligaments by draining the abscess, bandaging to reduce stress on the ligaments, and countering the bacterial infection with antibiotics or sulfonamides. Although the prognosis for complete recovery is poor, in most cases the foot heals sufficiently to allow adequate locomotion after ~2 mo. Control depends on early treatment and avoidance of the conditions that lead to ovine interdigital dermatitis. Although F necrophorum vaccines are available, they have not proved to be entirely satisfactory. Ovine Interdigital Dermatitis (Foot scald) Ovine interdigital dermatitis is a necrotizing condition of the interdigital skin due to a mixed infection with Fusobacterium necrophorum and Actinomyces pyogenes . It often precedes or accompanies footrot. These lesions often result in foot abscess (see Puncture Wounds of the Foot , Foot Abscess ). Similar injuries to the interdigital epithelium frequently result from “clay balling,” a condition in which balls of clay, molded into the shape of the interdigital space, harden and become difficult to dislodge and cause constant irritation and enhance bacterial invasion. The clinical appearance is characteristic, but similar conditions such as benign or virulent footrot must be excluded. Dermatophilosis (strawberry footrot, Dermatophilosis: Introduction) affects the hairy skin of the coronet and pastern. Viral diseases such as ulcerative dermatitis, contagious ecthyma, and foot-and-mouth disease may be excluded by flock history, clinical signs, and serology. Fusobacterium necrophorum may also infect the lesions caused by these diseases. Treatment and Control: Most lesions heal rapidly with the advent of dry conditions or removal to drier pastures. Virulent Footrot (VFR) (Malignant footrot, Contagious footrot) VFR is a specific, chronic, necrotizing disease of the epidermis of the interdigital skin and hoof matrix that begins as an interdigital dermatitis and extends to involve large areas of the hoof matrix. Because the infected tissue is destroyed, the hoof loses its anchorage and becomes detached. Footrot is contagious and, under suitable conditions, morbidity may approach 100%. The infection is also found in goats and deer but rarely in cattle. Etiology: VFR is due to a mixed infection of two gram-negative, anaerobic bacteria. Fusobacterium necrophorum is a normal resident of the sheep's environment, but infection depends on the presence of Dichelobacter nodosus , which does not survive for more than a few days in the soil or pastures. The transmission of footrot to healthy animals requires a warm, moist environment. Under these conditions, the interdigital stratum corneum becomes macerated; filaments of F necrophorum invade the superficial epidermis and induce ovine interdigital dermatitis (see Ovine Interdigital Dermatitis ). If D nodosus is in contact with the skin at this stage, VFR results. Injuries to the feet enhance the transmission of VFR, although it usually does not occur when the soil temperature is <40°F (4.5°C). Clinical Findings: The most obvious sign is lameness, which may be severe. Some sheep remain recumbent or on their brisket and knees, which tend to become hairless and ulcerated. Affected sheep lose body condition. Rams infected in the hindfeet may be unable to serve, and similarly, ewes with hindfeet lesions may be unable to bear the weight of a ram at service. Wool production is reduced. In early cases, examination of the feet may reveal nothing more than dermatitis similar to ovine interdigital dermatitis. As the disease progresses, the epidermal necrosis and separation of the horn spread further under the heel and sole, and finally the outer wall, so that the hoof may eventually be attached only at the coronet. The necrotic tissue has a characteristic odor. Myiasis is a common sequela and may extend to the sides of the sheep at sites where the infected feet are placed when the sheep lie down. Diagnosis: Early cases confined to the interdigital space may be confused with ovine interdigital dermatitis or BFR, and advanced ones with foot abscess (see Puncture Wounds of the Foot , Foot Abscess). In flocks affected with VFR, underrunning and separation of the hard horn of the hoof, usually of more than one foot, are characteristic. In foot abscess, there is a deeper invasion and discharge of necrotic and purulent material; usually, only one foot is affected. Dichelobacter nodosus usually can be identified in smears of stained necrotic material from footrot, although other bacteria predominate. Treatment: Treatment efforts may be directed toward temporary control of the disease or eradication from the flock. At certain times, eg, during a wet season, temporary control may be the only realistic goal. Treatment may be topical or parenteral. Topical treatment requires careful hoof paring to remove all underrun horn and to expose necrotic tissue. Bactericidal solutions are then applied by aerosol spray, footbathing, or footsoaking.
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The success rate for either topical or parenteral treatment is substantially improved if the treated sheep are kept in a dry environment after treatment. Prevention and Control: Flocks that are free of VFR may be kept free by preventing the introduction of D nodosus . Any sheep to be added to the flock should be examined, isolated for 1 mo, and then reexamined. Any vehicles or facilities in which unknown or infected sheep have been held must be cleaned and disinfected before placing uninfected sheep in them. Eradication: Eradication may be achieved only by eliminating all cases of virulent D nodosus infection and preventing its reintroduction. This can be done by replacing the affected flock with disease-free sheep or by culling affected sheep that do not respond readily to treatment and rigorously treating all new infections. Other ruminants (goats, deer, cattle) are potential sources of D nodosus and should be considered in eradication programs. Eradication should be undertaken only when the environment is dry; at other times, treatments should be directed toward control within the flock. Interdigital Fibroma An interdigital fibroma is a mass of fibrous tissue between the toes that may resemble a papilloma. If not removed, it grows upward between the first phalanges and may cause severe lameness. If it is detected early, surgical removal (cryosurgery and electrocautery) is successful. Lameness in Horses: Navicular Disease (Podotrochlosis, Podotrochlitis) Navicular disease is essentially a chronic degenerative condition of the navicular bursa and navicular bone that involves damage to the flexor surface of the bone and the overlying deep digital flexor tendon with osteophyte formation on the lateral and proximal borders of the bone. Thus, it is a syndrome with a complex pathogenesis rather than a specific disease entity. It is one of the most common causes of chronic forelimb lameness in horses but is essentially unknown in ponies and donkeys. Etiology: The exact cause is unknown, but it is likely to be multifactorial involving the navicular bone and its blood supply, the suspensory ligament, the coffin joint, the navicular bursa, and the deep digital flexor tendon. It is considered to be a disease of the more mature riding horse, but radiographic signs have been seen in 3-yr-olds. It may be partially hereditary; it is certainly associated with upright conformation of the forefoot. The conformation of the foot in chronic cases becomes abnormal; it is upright and narrow and has a small frog. Defective shoeing that inhibits the action of the frog and the quarters may be contributory. Concussion between the flexor tendon and the navicular bone can cause a local bursitis that leads to hyperemia and rarefaction of the bone with resultant alteration of the flexor surface of the bone. Clinical Findings and Diagnosis: Usually, the disease is insidious in onset. Attention is first directed to the affected foot or feet by the attitude of the horse when at rest. The horse relieves the pressure of the deep digital flexor tendon on the painful area by pointing or advancing the affected foot with the heel off the ground. If both forefeet are affected, they are pointed alternately. An intermittent lameness is manifest early in the course of the disease. The stride is shortened, and the horse may tend to stumble. A flexion test involving the distal forelimb usually produces a transient exacerbation of lameness. There may be soreness in the brachiocephalic muscles secondary to the changes in posture and gait, thus the frequent complaint of “shoulder lameness.” Clinical diagnosis is reasonably straightforward and is based on a complete history and careful physical examination. The lameness can be eliminated by palmar digital nerve block. Radiographic changes include a range of degenerative changes involving the navicular bone. Treatment: Because the condition is both chronic and degenerative, it can be managed in some horses but not cured. Nonsteroidal anti-inflammatory drugs such as phenylbutazone, along with proper foot management, extend serviceable soundness in some horses. Another therapy is isoxsuprine hydrochloride (0.27 mg/lb [0.6 mg/kg], PO, b.i.d. for 6-14 wk) in a paste form, which acts as a peripheral vasodilator, but recurrences follow cessation of therapy. Palmar digital neurectomy may render relief from pain and prolong the usefulness of the horse, but no neurectomy should be considered curative. Digital neurectomy can be accompanied by severe complications such as painful neuroma formation. Volar and higher neurectomy should never be done. A technique of desmotomy of the collateral sesamoidean ligament has also been described. By cutting this ligament, the concussive forces between the navicular bone and the deep digital flexor tendon are thought to be reduced. The results are preliminary and unsubstantiated.
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Although the prognosis is guarded to poor, a carefully designed therapeutic regimen can prolong the usefulness of most horses, and the competitive status of many. Laminitis (Founder, Fever in the feet) Traditionally defined as inflammation or edema of the sensitive laminae of the hoof, laminitis is now thought to be a transient ischemia associated with coagulopathy that leads to breakdown and degeneration of the union between the horny and sensitive laminae. In refractory cases, rotation of the pedal bone is a common sequela that may progress to perforation of the sole. The disease is a local manifestation of a more generalized metabolic disturbance, and the hoof problems are classified as acute, subacute, or chronic. It can occur in the forefeet, all four feet, or occasionally only in the hindfeet. Etiology: The most common causes of laminitis are ingestion of excess carbohydrate (grain overload), grazing of lush pastures (especially in ponies), and excess exercise and concussion in an unfit horse. It also may occur secondary to postparturient metritis, endotoxemia, colic and enteritis, or administration of an excess of corticosteroid or some other medicament. The risk is higher in ponies and in horses that are overweight and unfit. There is a higher incidence of the acute and subacute forms whenever there is a flush of new grass. The initial change in acute laminitis is ischemia of the lamellar arterioles and venules. The arterial blood is then shunted to the venous return via the many anastomotic blood vessels in the foot (especially at the coronary band) and bypasses the corium; the result is stagnation of blood and functional congestion and thromboembolism of the capillary beds. Laminar necrosis contributes to rotation. These disturbances in the circulation to the foot, which initially are reversible, probably cause the exhibited pain. However, if the condition becomes protracted and there is chronic hypoxia and a lack of essential sulfur-containing amino acids for the corium, then slowing or cessation of keratinization occurs between the stratum germinativum and keratogenous zone. The end result, in mild cases, is production of “laminitic rings”; in severe cases, pedal rotation or complete separation of the hoof from the underlying tissues occurs. The separation of the horny and sensitive laminae is due to ischemia, faulty keratinization, and the constant pull of the deep flexor tendon on the pedal bone, along with the upward push of the toe as the horse stands. There is some support at the back of the pedal bone from the deep digital flexor tendon and the digital cushion; however, these supportive structures may serve as a fulcrum, resulting in pedal bone rotation. If the separation occurs rapidly, the pedal bone may “sink” within the hoof. In chronic cases, the corona of the pedal bone may penetrate the sole just in front of the frog. The prognosis in severe cases is poor because the changes become irreversible and secondary infection is common. In subacute and chronic cases, the rotation of the pedal bone occurs relatively slowly. The sole tends to become convex and thicken, and the hoof alters shape to accommodate the new position. Clinical Findings: In acute laminitis, the horse is depressed and anorectic and stands reluctantly. Resistance to any exercise is marked, and the normal stance is altered in attempts to relieve the weight borne by the affected feet. If forced to walk, the horse shows a slow, crouching, short-striding gait. Each foot, once lifted, is set down as quickly as possible. Usually, heat is apparent in the whole hoof, especially near the coronary band. An exaggerated and bounding pulse can be palpated and may be visible in the digital arteries. Pain can cause muscular trembling, and a fairly uniform tenderness can be detected when pressure is applied to the feet. The pedal bone may rotate during or after the acute stage if efficacious treatment is not given rapidly. Radiographic evidence of rotation can be present as early as the third day. The subacute case may exhibit any or all of the above clinical signs but to a lesser degree. The acute and subacute forms of laminitis tend to recur at varying intervals and may develop into the chronic form. Chronic laminitis is characterized by changes in the shape of the hoof and usually follows one or more attacks of the acute form. Bands of irregular horn growth (laminitic rings) may be seen in the hoof, close at the toe and diverging at the heel. The hoof itself becomes narrow and elongated, with the wall almost vertical at the heel and horizontal at the toe. Diagnosis: In acute and severe laminitis, diagnosis is based on the history (eg, grain overload) and posture of the horse, increased temperature of the hooves, a hard pulse in the digital arteries, and reluctance to move. Divergence of ≥11° indicates a guarded to unfavorable prognosis for return to performance. Treatment: Acute laminitis constitutes a medical emergency because pedal rotation can occur rapidly. In acute laminitis, especially in cases of grain overload, mineral oil is indicated; 1 gal. (4 L) PO acts as a laxative and tends to prevent absorption of toxic material from the GI tract. Traditionally, cold packs or ice packs applied to the affected feet have been advocated, but recent evidence suggests that hot packs used early in the course of the disease may be more beneficial. Antihistamines are of doubtful value during
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acute lameness, but isoxsuprine hydrochloride paste, a peripheral vasodilating agent, may be of value. Heparin (40 u/kg, t.i.d. for 3 days) has been used because of the suspected accompanying coagulopathy and thromboembolism; however, heparin therapy in the horse has been associated with RBC clumping which, in a dehydrated animal, could aggravate dynamics of local blood flow in the feet. Flunixin meglumine and phenylbutazone are the preferred anti-inflammatory agents, and meclofenamic acid also has been of value; however, all three may be toxic. Phenoxybenzamine hydrochloride which is an α-adrenergic blocker that causes vasodilation for up to 24 hr, has been used in severe and acute cases of laminitis. However, it may cause depression and should be avoided in horses in shock. Experimentally, a combination vaccine consisting of a killed Salmonella mutant bacterin, an endotoxoid, and an aluminum hydroxide adjuvant has been effective in reducing the endotoxin-related complications of laminitis. Digital nerve blocks in the early stages of the disease permit the horse to be walked, which increases the arterial blood flow through the terminal arch. However, nerve blocking and walking are contraindicated once pedal rotation has begun. Treatment of chronic laminitis has consisted of attempting to restore the normal alignment of the rotated coffin bone and encouraging frog pressure by lowering the heels, removing excess toe, and protecting the dropped sole. Puncture Wounds of the Foot (Pricked foot, Nail bind, Nail prick, Subsolar abscess) Puncture wounds are usually the result of poor farriery technique but can occur when a horse steps on a penetrating foreign body. “Nail bind” implies that a nail has been driven close to the sensitive structures of the foot, causing acute pain. “Nail prick” means the corium has been penetrated. There is increased heat and pain in the foot, which progress to the coronary band as abscess formation proceeds. Subsequently, there is edematous swelling of the pastern and fetlock areas. In neglected cases, there is draining at the coronary band after 2-3 wk. Diagnosis is made by confirming the site of pain by pulling the shoe, using hoof testers, and paring the suspect area to locate the foreign body or its track. Prompt treatment with disinfectants and poultices is important for nail bind and nail prick. If present, foreign bodies must be found and removed, and the infected area pared with a hoof knife to establish adequate drainage. All horses with puncture wounds should be immunized against tetanus. If pain is severe, a palmar nerve block provides temporary relief. Thrush Thrush is a degeneration of the frog with secondary bacterial infection that begins in the central and collateral sulci. It results from poor management and hygiene that permit horses to stand in wet conditions for prolonged periods and from failure to clean the hooves regularly. It is more common in the hindfeet. Treatment should begin by providing dry, clean standings and cleaning out the hoof with removal of all macerated horn. Bucked Shins (Sore shins, Saucer fractures) Bucked shins is a painful, acute periostitis on the cranial surface of the large metacarpal or metatarsal bone. It is seen most often in the forelimbs of young Thoroughbreds (2-yr-olds) in training and racing and is much less common in Standardbreds. This injury is generally brought about by concussion in young horses in which the bones are not fully conditioned. Microfractures (ie, stress fractures) are believed to be involved. There is a warm, painful swelling on the cranial surface of the affected bone. The horse is usually lame initially, the stride is short, and the severity of the lameness increases with exercise. Suspensory Desmitis Injuries of the suspensory ligament (superior sesamoidean ligament or interosseous muscle) are common injuries in both forelimbs and hindlimbs of horses. Lesions are frequently restricted to the proximal one-third of the ligament, to the body or middle one-third, or to one or both branches. Proximal Suspensory Desmitis: The term proximal suspensory desmitis is restricted to lesions confined to the proximal one-third of the metacarpus (or metatarsus). It is relatively common and affects both forelimbs and hindlimbs of horses of all ages. In contrast to lesions involving the body or branches (or both) of the suspensory ligament, there is usually associated lameness or poor performance or poor action. The condition may occur unilaterally or, less commonly, bilaterally. It sometimes occurs in association with more distal limb pain (eg, navicular disease) and is frequently seen in horses with poor
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mediolateral or dorsopalmar foot balance. Straight hock conformation or hyperextension of the metatarsophalangeal joints may predispose to this type of injury. Lameness can vary in degree from mild to severe and, in early cases, is generally exacerbated by work and improved by rest. Forelimb lameness may be accentuated by flexion of the fetlock and interphalangeal joints but is generally unaffected by carpal flexion, whereas hindlimb lameness may be increased by flexion of the fetlock and interphalangeal joints or by flexion of the hock and stifle joints. In acute cases, there may be localized heat in the proximal metacarpal (or metatarsal) region with or without periligamentous soft-tissue swelling. In more chronic cases, frequently no palpable abnormality can be detected. Diagnosis is made by local anesthesia and ultrasound examination, which usually demonstrates diffuse or central hyopechoic areas with hyperechogenic foci in chronic cases. Treatment is by stall rest, followed by a graduated program of exercise combined with correction of foot imbalance. Desmitis of the Body of the Suspensory Ligament: This is principally an injury of racehorses. Injuries usually affect the forelimb of Thoroughbreds, whereas they occur in both forelimbs and hindlimbs in Standardbreds. Treatment is aimed at reducing inflammation by systemic nonsteroidal anti-inflammatory drugs, hydrotherapy, and controlled exercise. Desmitis of the Medial or Lateral Branch of the Suspensory Ligament: This relatively common injury occurs in all types of horses in both forelimbs and hindlimbs. Usually only a single branch in a single limb is affected, although both branches may be affected, especially in hindlimbs. Foot imbalance is often recognized in affected horses, and this may be a predisposing factor. The clinical signs depend on the degree of damage and the chronicity of the lesion(s) and include localized heat and swelling. Swelling is often due to local edema of the affected branch. Pain is usually elicited either by direct pressure applied to the injured branch or by passive flexion of the fetlock. Diagnosis is based on clinical signs and ultrasonographic examination. Hindlimb Tendon Ruptures Laceration of the entire Achilles tendon involving both the gastrocnemius and superficial flexor tendons is rare. The hock drops to the ground and is unable to bear weight. The prognosis is grave. Gastrocnemius muscle rupture is more common and can result from excess stress applied to the hock (eg, sudden stopping). Injuries to the extensor tendons, the long and lateral digital extensors, frequently accompany hindlimb lacerations. If one tendon is involved, the prognosis is usually good. If both extensor tendons are severed, the horse may be left with a gait deficit for performance, but it may be useful for slow speeds or for breeding. Conservative treatment leads to wound healing, but surgical repair and casting should be considered if both tendons are severed or if performance status is desired. Rupture of the superficial and deep flexor tendons sometimes occurs as a racing injury or accompanies lacerations. These are serious injuries with marked lameness and varying degrees of overextension of the fetlock and pastern. Treatment involves surgical repair with splinting and casting the limb, but the prognosis is poor for future performance. Gonitis Gonitis is an inflammation of the stifle leading to degenerative joint disease. The joint is complex, and gonitis may be precipitated by multiple causes, including osteochondrosis, persistent upward fixation of the patella, injuries to the medial or lateral collateral ligaments, injuries to the cruciate ligaments or the menisci, erosions of the articular cartilage, or bacterial infection of the joint from puncture wounds or of hematogenous origin (eg, pyosepticemia). Signs vary with the cause and extent of the pathologic changes. Patellar Luxation True dislocation of the patella is uncommon in horses. When it does occur, it is usually a serious injury and the lateral luxation is readily apparent. In some breeds, a congenital form of lateral luxation occurs similar to that seen in small dogs ( Patellar Luxation). The most frequent problem involving the patella is upward fixation or locking of the medial patellar ligament over the proximal part of the medial femoral trochlear ridge. Some pony breeds may have a hereditary predisposition, but patellar luxation is also seen in immature animals with poorly developed thigh muscles. It may be uni- or bilateral. In many cases, a general improvement in fitness and muscle tone of the hindquarters effects a cure. In the more severe and persistent cases, desmotomy of the medial patellar ligament is indicated. However, desmotomy, which has been commonly used in the past, is currently in disfavor. A fragmentation of the distal extremity of the patella is believed to follow the surgery, particularly if postoperative exercise is initiated early. When surgery is done, rest should be sufficient (eg, 4-6 wk) to permit complete healing before training is resumed.
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Coxitis (Osteoarthritis of the hip) Coxitis is inflammation of the hip that leads to osteoarthritis of the coxofemoral joint. Most cases are traumatic in origin, secondary to falls or being cast (within a stall) in recumbency; however, tears of the rim of the acetabulum or fractures through the acetabulum, and localization of a systemic infection, particularly pyosepticemia in young animals, have occurred. Both a supporting- and a swinging-leg lameness are noted. In severe cases, the leg may be carried. In less severe cases, the gait is rolling, ie, the affected quarter is elevated as weight is borne on the leg. Rectal palpation may reveal an enlargement over the acetabulum, particularly if a fracture through it has occurred. Radiography of the joint confirms the diagnosis. The prognosis is poor. Rest is indicated. Developmental Orthopedic Disease: Overview Developmental orthopedic diseases of horses constitute an important group of conditions that includes osteochondrosis, physeal dysplasia, acquired angular limb deformities, flexion deformities, and cuboidal bone malformations. Osteochondrosis (Osteochondritis dissecans, Dyschondroplasia) Osteochondrosis (see also Osteochondrosis: Introduction , Osteochondrosis) is one of the most important and prevalent developmental orthopedic diseases of horses. Although its specific etiology is not known, it is considered to arise from a focal disturbance in endochondral ossification. The term osteochondrosis is currently used to describe the clinical manifestation of the disorder; however, the term dyschondroplasia is preferred when referring to early lesions because primary lesions occur in cartilage. Osteochondrosis has a multifactorial etiology that includes rapid growth, overnutrition, mineral imbalance, and biomechanics (ie, trauma to cartilage). Genetics has been implicated in some breeds (eg, Standardbred and Swedish Warmblood). The condition mainly affects articular growth cartilage, but the metaphysis may also be involved. If the physeal metaphyseal cartilage is affected, bone contours and longitudinal growth are disturbed (see physitis , Physitis). Involvement of articular cartilage at the periphery of joint surfaces leads to regressive changes at the joint margins, dissecting lesions, and the formation of flaps (osteochondritis dissecans). Central articular lesions, because of weightbearing effects, involve focal retention of cartilage within the subchondral bone (see subchondral cysts, Subchondral Cystic Lesions). Axial skeletal involvement includes vertebral articular facets, and this may lead to stenosis of the vertebral canal and, ultimately, ataxia and proprioceptive deficits (ie, wobbler syndrome). Clinical Findings: The clinical signs of equine osteochondrosis are difficult to characterize specifically because of the wide range of lesions and sites involved. In severe cases, other signs of developmental orthopedic disease also may be apparent. Furthermore, lesions of dyschondroplasia do not always progress to osteochondrosis and produce clinical signs. These signs may begin with mild stiffness or lameness, but if there is superimposed biomechanical trauma, the joint damage progresses to pain and lameness or loss of performance. The most common sign of osteochondrosis is a nonpainful distention of an affected joint (eg, gonitis, bog spavin). Clinical signs may be divided broadly into two categories; those occurring in foals <6 mo old and those occurring in older animals. Often the first sign noted in foals is a tendency to spend more time lying down. This is accompanied frequently by joint swelling, stiffness, and difficulty keeping up with other animals in the paddock. An accompanying sign may be the development of upright conformation of the limbs, presumably as a result of rapid growth. Fetlock osteochondrosis is particularly seen in younger foals (<6 mo old). Marked lameness is not usually a feature of equine osteochondrosis, although it does occur with damage in some sites. For example, lesions in the shoulder frequently produce moderate to severe lameness, muscle atrophy, and pain on joint flexion. The true origin of pain in osteochondrosis is unknown. Horses often exhibit severe pathologic changes without showing much pain or distress in contrast to some situations seen in some other species and sites (eg, canine elbow). The main signs in yearlings or older horses are stiffness of joints, flexion responses, and varying degrees of lameness. These signs are usually associated with the onset of training and, therefore, suggest a biomechanical influence and an activation of subclinical or “silent” lesions. Diagnosis: Clinical diagnosis can often be made on the basis of signalment and signs. More definitive diagnosis requires the use of some specific clinical aids. Radiographic examination has been the traditional method of confirming diagnosis; however, early lesions involving cartilage without significant subchondral bone damage will not be visualized. In the distal limb, oblique views may be helpful; in the hock, because the most common site of a lesion is the distal
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intermediate ridge of the tibia, the best view is a plantarolateral/dorsomedial oblique. Ultrasound examination of the swollen joints can also be helpful and can delineate articular damage and “joint mice.” The most accurate way to confirm diagnosis is by arthroscopy, and most of the predilection sites are accessible except for the cervical articulations. Treatment and Management: Management of clinical cases of osteochondrosis depends on the site and severity of signs. Mild cases recover spontaneously, and a conservative approach may be appropriate. In young animals (<12 mo old), this involves restricted exercise for some weeks combined with a reduction in feed intake to slow the growth rate. Particular care should be taken to ensure appropriate mineral supplementation is indicated (eg, suspected copper deficiency). It is controversial whether correcting the diet, once signs have developed, will actually assist resolution, but it may help limit or prevent further cases on stud farms. Intra-articular medication with hyaluronic acid may be beneficial, and injection of long-acting corticosteroids may help reduce swelling and improve any associated synovitis. Lameness in Pigs in the Nursery By the time pigs are weaned, diseases that affect the locomotor system most likely will have resolved spontaneously, responded to aggressive therapy, or resulted in death, or the pig may have been culled. Because pigs that survive episodes of polyarthritis generally remain lame, have one or more swollen “knotty” joints, and are in poor condition, they should be culled. Infectious Arthritis or Polyarthritis: Causes include Mycoplasma hyorhinis , Haemophilus parasuis , or Erysipelothrix rhusiopathiae , which occur sporadically among groups of pigs or herds. The clinical signs seen in infections caused by M hyorhinis and H parasuis (Glässer's disease, Glässer's Disease: Introduction ) are similar, because both organisms cause polyarthritis and polyserositis. The upper respiratory tract of the sow is the source of the organism for the baby pig and, presumably, some older pigs are also carriers and spread infection. Infection with M hyorhinis usually results is moderate morbidity and low mortality, but H parasuis can cause infection in 50-75% of pigs and up to a 10% mortality. Outbreaks of Glässer's disease have been particularly severe in SPF herds. Fever is associated with both conditions but can be highest in Glässer's disease (>107°F). A shifting lameness occurs, and joints are warm and swollen. Pneumonia develops with both conditions, and sometimes H parasuis causes neurologic signs. Susceptible, stressed, adult pigs can succumb to M hyorhinis with a higher fever and a more severe lameness than develop in nursery pigs. Boars may develop scrotal edema and discomfort. At necropsy, polyarthritis and polyserositis are seen with both mycoplasmal arthritis and Glässer's disease, and pneumonia may have developed. In Glässer's disease, there may also be a meningitis. Stunted pigs in the grower/finisher group that have chronic, severe, fibrinous, fibrinopurulent, or fibrous pleuritis, peritonitis, and arthritis could have been affected by either condition earlier in their lives and are best culled rather than kept as a source of infection for other pigs. Diagnosis is based on clinical signs, necropsy findings, and the isolation of the organism; however, if any treatment has been instituted, the chances of finding the organisms are reduced. Treatment for either disease must be aggressive and start soon after the onset of clinical signs. The effectiveness of treating M hyorhinis infections with tylosin or lincomycin has been variable. Provided that the organism is susceptible to an antimicrobial compound, treatment of Glässer's disease with penicillin, ampicillin, streptomycin, tetracyclines, or sulfa drugs has been more successful. Erysipelas: Although acute erysipelas can occur in nursery pigs, it may be more typical of the growing/finishing pigs . Vertebral Deformities: Kyphosis or lordosis and cuneiform deformities of vertebrae have been seen in weaned pigs, but a cause has not been identified. “Humpy back” pigs are seen sporadically in some herds; the spine is curved in the vertical plane such that the lumbar vertebrae are higher than the thoracic vertebrae, and there is a “kink” between the two segments. The condition may have a genetic predisposition. Lameness in Gilts, Sows, and Boars Lameness caused by Mycoplasma hyosynoviae , or acute or chronic erysipelas can cause an incapacitating lameness. Polyarthritis and polyserositis caused by M hyorhinis are seen occasionally in these older pigs. Rickets, Osteomalacia, and Osteoporosis: These syndromes can affect one or more age groups of pigs with various clinical outcomes. Most pigs, including breeding stock, are slaughtered before their skeleton has fully matured; however, some growth plates are functional up to 3½ yr of age and, therefore, are susceptible to rachitic and other changes. Osteomalacia is characterized by an excess of unmineralized or poorly mineralized osteoid that forms as bone remodeling occurs (or does not occur). Rickets (see Lameness in Pigs in the Grower/Finisher Areas) is the component of
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osteomalacia that affects the growth plate. The pathogenesis of osteoporosis is different from that of either rickets or osteomalacia. Established bone loses mineral and, therefore, mass by a process of osteolysis. Consequently, particularly in sows late in gestation, during lactation, or soon after weaning, bones become weaker and are susceptible to fractures. A gilt selected for breeding stock that has had clinically normal skeletal development must meet the needs not only of her own skeleton, but within 35-45 days of breeding, must also provide mineral for growing fetuses. This may result in development of osteomalacia, which is compounded by secretion of mineral in her milk when lactation begins. The gilt may soon draw on her skeletal reserves and become osteoporotic. Because sows can become pregnant within 7 days of weaning, there is little time for recovery of skeletal mass between one breeding cycle and the next, and so the skeleton becomes progressively weaker. Therefore, it is not surprising that considerable numbers of first- and second-litter sows are culled because of fractures and lameness. The most frequent sites of fractures are the humerus, femur, lumbar vertebrae, and occasionally ribs. Multiple vertebral body fractures have been described in gilts that were considered to have been exposed to stray electrical voltage. Whatever the factors that precipitate the fractures, affected sows are in pain and are either severely lame and unwilling to move or paraplegic. Diagnosis is based on a history of acute lameness or paraplegia in pregnant, lactating, or recently weaned gilts or sows. Sometimes, crepitus can be detected in affected limbs. A neurologic examination can aid in locating spinal lesions. Affected sows should be culled after an early diagnosis, but they have little salvage value. Prevention through adequate nutrition and exercise for the gilts and sows is the best (and only) way to curtail the problem. Osteomyelitis and Spinal Abscesses: In addition to the causes discussed under grower/finisher pigs (Lameness in Pigs in the Grower/Finisher Areas), osteomyelitis may also develop secondary to a fracture of a vertebra or an epiphyseal separation. It is reasonable to assume that occasional “showering” with organisms from superficial wounds, abscesses, or the respiratory or GI tracts can be a source of infection. Actinomyces pyogenes seems to be a frequent cause of the suppuration and abscessation. Osteomyelitis of the ulnar epiphysis in young boars and sows has been reported. Degenerative Joint Disease (Osteochondrosis Dissecans, Osteoarthritis, Osteoarthrosis), Dyschondroplasia (Osteochondrosis), and Leg Weakness: These syndromes cause major losses in commercial pig herds and are more important than ever given the increased scale of production in many herds and the shift toward pigs that grow faster, are more muscular, and finish heavier. Another relevant change is the trend toward a relatively small number of producers of hybrid breeding stock meeting the needs of new and expanding herds. Osteochondrosis and osteoarthritis occur in all the major breeds of commercial pigs; they are particularly important and common because they are not eliminated by crossbreeding. In addition, epiphyseolysis and epiphyseal separation may be precipitated by weakening of underlying growth plates if they are affected by osteochondrosis. Degenerative joint disease (DJD) can also decrease growth rate in lame finishing pigs, and there is a risk of partial carcass condemnations if affected joints are swollen. Although lesions that precede or develop into DJD or result in limb deformities begin to develop in younger pigs, clinical problems are not usually seen until pigs are >4-8 mo old. Frequently, the fastest growing, most muscular, heaviest pigs are affected. Given time, some pigs (if not culled) recover from episodes of lameness, but any deformities may remain. Clinical signs vary with the site and extent of lesions and can range from stiffness and a shortened stride or a stride affected by an angular limb deformity to a three-legged lameness or an inability to stand. Pigs that “walk” on flexed carpuses usually have severe DJD in the elbows, and pigs that “tuck” their pelvic limbs under their abdomen or develop kyphosis often have DJD that affects stifles, tibial tarsal bones, or joints on intervertebral processes. If epiphyseal separation of the femoral head has occurred, the pig has difficulty in standing and initially will not use the affected limb. A pig that has unilateral separation of the ischiatic tuberosity also has difficulty standing; if both tuberosities are affected, the pig has a hopping gait for a few steps and then collapses. The severity of clinical signs in any of these conditions varies individually, and seemingly less severely affected joints may be protected by the gait if they are more painful than other degenerating joints. Severe joint lesions have been seen in pigs that did not appear to be lame. In pigs that have limb deformities (eg, osteochondrosis affecting the distal ulnar growth plate), thickened, irregular growth plates are seen on radiographs or at necropsy. In degenerating joints, there is an excess of yellow synovia, and synovial villi may have proliferated. There are various irregularities of the articular surface, including folds in the cartilage, clefts, flaps of cartilage, and in severe cases, craters and exposed subchondral bone. In chronic cases, osteophytes develop, detached fragments of cartilage become embedded in the synovium and start to ossify, and craters fill with fibrocartilage. If vertebral joints are affected, vertebrae eventually fuse. Growth plates that are most severely affected by dyschondroplasia are those of the distal part of the ulna (which can easily be monitored radiographically) and the ribs, whereas sites most often affected by DJD include the elbow, stifle, hock, and intervertebral synovial joints. The pathogenesis of lesions is poorly understood, but foci of poorly mineralized cartilage persist in the metaphyses and epiphyses (and may be points of weakness), or foci of necrotic chondrocytes develop in the middle region of the
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articular-epiphyseal cartilage complex. It is postulated that there is failure of the vasculature that supplies or penetrates the sites where lesions develop or that chondrocytes are not functioning normally to maintain the homeostasis of the cartilage or to promote endochondral ossification. Crossbreeding for hybrid vigor does not solve the problem. The fastest growing pigs in a group seem to have the greater propensity for lesions developing in either growth plates or joints, but once slower growing pigs reach the body weight of their faster growing peers, lesions are comparable. Growth hormone may affect chondrocyte metabolism and thereby influence the onset of articular lesions. Footrot or Septic Laminitis: This can develop in any age pig but can cause serious losses in breeding pigs. Footrot is seen in both confinement and semiconfinement systems, with morbidity of 20-68%. Often a single limb is affected, and the lameness progresses to the point that the pig is three-legged lame. Lesions usually develop gradually, and the foot becomes swollen. Lesions vary in severity and can include heel erosions, separation along the white line, toe erosions, sole erosions, false sandcracks, deep necrotic ulcers, sinuses at the coronary band, and chronic fibrosis. A mixture of organisms has been isolated from the lesions or identified in smears from lesions and tissue sections. These included Actinomyces pyogenes , Fusobacterium necrophorum , Borrelia suilla , and a mixture of gram-negative and gram-positive cocci and rods. A diagnosis is made from the clinical signs and a thorough evaluation of the feet. If there is a herd problem, feet should be evaluated at the slaughterhouse. To ensure that lesions are severe enough to be the cause of the lameness, it is advisable to section feet parallel with the sole to determine if the soft tissues and bones within the foot are infected. Treatment with penicillin has proved effective (200,000 u into the lesion or 600,000 u, IM), but success decreases with chronicity of the lesion. Prevention involves improving the nature and cleanliness of the flooring. As replacement gilts mature, biotin supplementation seems to enhance the quality of the hoof wall. Foot baths that include copper sulfate, formalin, or oxytetracycline and paraffin help to prevent or alleviate lesions. Success in increasing longevity of pigs that have had digits amputated has been variable. Lameness In Small Animals: Introduction Signs of musculoskeletal disorders include weakness, lameness, limb swelling, and joint dysfunction. Motor or sensory neurologic impairment may occur secondary to neuromuscular lesions. Abnormalities of the musculoskeletal system may also affect other organs of the endocrine, urinary, digestive, hemolymphatic, and cardiopulmonary systems. Evaluation of musculoskeletal disease is aimed at localizing and defining the lesion(s). Diagnosis requires accurate review of the signalment, history, and physical status of the animal. A lameness examination is critical in determining a diagnosis. The lameness examination is a key feature in identifying the musculoskeletal lesion. With a forelimb lameness, the head is elevated during weight bearing on the unsound limb. The stride is also shortened on the affected side. For hindlimb lameness, the head is dropped during weight bearing of the affected limb. Limbs should be assessed from a distal to proximal manner, and bones, joints, and soft tissue should be palpated. Abnormalities that should be noted include swelling, pain, instability, crepitation, reduced range of motion, and muscle atrophy. Feline Hypokalemic Polymyopathy Feline hypokalemic polymyopathy is a generalized metabolic muscle weakness disorder in cats secondary to hypokalemia associated with excessive urinary depletion or inadequate dietary intake. Extracellular hypokalemia causes muscle cell membrane hyperpolarization and secondary excessive permeability to sodium. This leads to hypopolarization of the muscle cell and subsequent weakness. Clinical signs include generalized weakness, ventroflexion of the neck, abnormal gait, anorexia, and muscle pain. The neurologic examination is normal. Serum chemistries reveal hypokalemia (<3.5 mEq/L) and increased creatinine and creatine kinase. The urine has a low specific gravity, and potassium excretion is increased. Treatment is by potassium supplementation, given orally (5-8 mEq/day) or IV in cats with profound hypokalemia. Prognosis is excellent with early diagnosis and treatment. Hip Dysplasia Hip dysplasia is a multifactorial abnormal development of the coxofemoral joint in large dogs that is characterized by joint laxity and subsequent degenerative joint disease. Excessive growth, exercise, nutrition, and hereditary factors affect the occurrence of hip dysplasia. The pathophysiologic basis for hip dysplasia is a disparity between hip joint muscle mass and rapid bone development. As a result, coxofemoral joint laxity or instability develops and subsequently leads to degenerative joint changes, eg, acetabular bone sclerosis, osteophytosis, thickened femoral neck, joint capsule fibrosis, and subluxation or luxation of the femoral head. Clinical signs are variable and do not always correlate to the radiographic abnormalities. Lameness may be mild, moderate, or severe, and is pronounced after exercise. A “bunny-hopping” gait is sometimes evident. Joint laxity (Ortolani's
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sign), reduced range of motion, and crepitation and pain during full extension and flexion may be present. Radiography is useful in delineating the degree of arthritis and planning of medical and surgical treatments. Standard ventrodorsal views of sedated or anesthetized animals can be graded by the Orthopedic Foundation for Animals, or stress radiographs performed and joint laxity measured (PennHIP). Treatments are both medical and surgical. Mild cases or nonsurgical candidates (due to health or owner constraints) may benefit from weight reduction, restriction of exercise on hard surfaces, controlled physical therapy to strengthen and maintain muscle tone and antiarthritic drugs (eg, aspirin, corticosteroids, and carprofen) and possibly joint fluid modifiers. Surgical treatments include pectineal myotenectomy to reduce pain, triple pelvic osteotomy to prevent subluxation, femoral head and neck resection to reduce arthritis, and total hip replacement for optimal restoration of joint and limb functions. Additionally, femoral corrective osteotomies can be performed to reduce femoral head subluxation, although degenerative arthritis may persist. Prognosis is highly variable and depends on the overall health and environment of the animal. In general, if surgery is indicated and performed correctly, it is beneficial. Animals on which surgery is not performed may require an alteration in lifestyle to lead a comfortable existence. Degenerative Arthritis (Degenerative joint disease) Progressive deterioration of articular cartilage in diarthrodial joints is characterized by hyaline cartilage thinning, joint effusion, and periarticular osteophyte formation. Joint degeneration can be caused by trauma, infection, immunemediated diseases, or developmental malformations. The inciting cause initiates chondrocyte necrosis, release of degradative enzymes, synovitis, and continued cartilage destruction and inflammation. Abnormal cartilage congruency and joint capsule anatomy can further lead to alteration in normal joint biomechanical function. Pain and lameness develop secondary to joint dysfunction or muscle atrophy and to limb disuse. Clinical signs of degenerative joint disease include lameness, joint swelling, muscle atrophy, pericapsular fibrosis, and crepitation. Radiographic changes in the joint include joint effusion, periarticular soft-tissue swelling, osteophytosis, subchondral bone sclerosis, and possibly narrowed joint space. Arthrocentesis may be unremarkable or yield minor changes in color, turbidity, or cell counts of synovial fluid. Treatments can be medical or surgical. Nonsurgical therapies include weight reduction, controlled exercise on soft surfaces, and therapeutic application of warm compresses to affected joints. Nonsteroidal anti-inflammatory drugs (eg, aspirin, phenylbutazone, or carprofen) will reduce pain and inflammation. Corticosteroids will also suppress prostaglandin synthesis and subsequent inflammation, but short-term use is advised to prevent iatrogenic Cushing's syndrome, cartilage degeneration, and intestinal perforation. Joint fluid modifiers such as glycosaminoglycans or sodium hyaluronate prevent cartilage degradation, although results of objective clinical trials are not available. Surgical options include joint fusion (arthrodesis), most frequently performed on the carpus and tarsus; joint replacement, such as total hip replacement; joint excision, such as femoral head and neck osteotomy; and amputation. Prognosis is variable and depends on the location and severity of the arthropathy. Septic Arthritis Infectious arthritis is most frequently associated with bacterial agents such as staphylococci, streptococci, and coliforms. Causes include hematogenous spread or penetrating trauma, including surgery. Other agents producing a septic arthritis include rickettsia (Rocky Mountain spotted fever, ehrlichiosis) and spirochetes (borreliosis). Clinical signs of septic arthritis include lameness, swelling, pain of affected joint(s), and systemic signs of fever, malaise, anorexia, and stiffness. Radiography may reveal joint effusion in early cases and degenerative joint disease in chronic conditions. Arthrocentesis will reveal increased WBC, especially neutrophils. The synovial fluid may be grossly purulent. Bacterial culture and antimicrobial sensitivity testing may confirm the diagnosis. Serologic testing is used for nonbacterial agents. Treatment is with appropriate IV and oral antibiotics, joint lavage, and surgical debridement in severe cases. Immune-mediated Arthritis Inflammatory polyarthritis secondary to deposition of immune complexes can produce erosive (destruction of articular cartilage and subchondral bone) or nonerosive (periarticular inflammation) forms of joint diseases. Rheumatoid arthritis, Greyhound polyarthritis, and feline progressive polyarthritis are examples of erosive arthritides. Systemic lupus erythematosus (SLE) is the most common form of nonerosive arthritis. Clinical signs are lameness, multiple joint pain, joint swelling, fever, malaise, and anorexia. Clinical signs commonly wax and wane. Diagnosis is aided by radiography, biopsy, arthrocentesis, and serologic testing. Radiography reveals periarticular swelling, effusion, and joint collapse plus subchondral bone destruction in erosive conditions. Arthrocentesis reveals

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synovial fluid with reduced viscosity and increased inflammatory cell counts. Biopsy of synovial tissue reveals mild to severe inflammation and cellular infiltrates. Serologic testing is performed for rheumatoid factor and antinuclear antibodies. Treatment involves anti-inflammatory medications (eg, corticosteroids) and chemotherapeutic agents (eg, cyclophosphamide, azathioprine, or methotrexate). Prognosis is guarded due to relapses and inability to determine the inciting cause of the autoimmune reactions. Neoplastic Arthritis Synovial cell sarcoma is the most common malignant tumor involving joints. The tumor arises from primitive mesenchymal cells outside of the synovial membrane. Clinical signs include lameness and joint swelling. Radiography reveals soft-tissue swelling and a periosteal reaction. Pulmonary metastasis is detected in ~25% of animals at initial examination. Biopsy reveals evidence of a soft-tissue tumor. Limb amputation is the treatment of choice. Cranial Cruciate Ligament Rupture Rupture of the cranial cruciate ligament is most frequently due to excessive trauma and a possibly weakened ligament secondary to degeneration, immune-mediated diseases, or conformational defects (straight-legged dogs). Most injuries involve a midsubstance tear, although bone avulsion at the origin of the ligament is possible. Instability of the stifle joint after rupture of the cranial cruciate ligament can lead to medial meniscal injury, joint effusion, osteophytosis, and joint capsule fibrosis. Clinical signs involve lameness, pain, medial joint swelling, effusion, crepitation, excessive cranial laxity of the tibia relative to the femur (drawer motion), and increased internal tibial rotation. Partial cranial crucial ligament tears are characterized by a reduced cranial laxity, usually more pronounced in flexion. Medial meniscal injury may be identified by a clicking sound during locomotion or flexion and extension. A tibial compression test (flexion of the hock and cranial displacement of the tibial tuberosity) can also be used to demonstrate insufficiency of the cranial cruciate ligament. Radiography will reveal joint effusion and signs of degenerative joint disease in chronic injuries. Arthrocentesis may reveal mild cellular increases and hemarthrosis; arthroscopy can confirm the diagnosis but requires specialized equipment. Treatments include medical and surgical therapies. Weight reduction, controlled physical therapy, and nonsteroidal anti-inflammatory drugs (eg, aspirin, carprofen, phenylbutazone) alleviate pain and discomfort from inflammation and degenerative joint disease. Surgical stabilization of the stifle joint is recommended for active dogs. Extracapsular techniques include fascial suturing, fabella to tibial tuberosity imbrication sutures, and cranial transposition of the fibular head. Hypertrophic Osteodystrophy Hypertrophic osteodystrophy is a developmental disorder of the metaphyses in long bones of young, large, and giant breeds of dogs. The exact etiology is unknown, but vitamin C deficiency, excessive dietary supplementation, and infection have been suspected. The pathophysiology is based on metaphyseal vascular impairment leading to a failure in ossification and trabecular necrosis and inflammation. Clinical signs include bilateral metaphyseal pain and swelling in the distal radius and ulna, fever, anorexia, and depression. Clinical signs may be periodic. Angular limb deformities may develop in severely affected dogs. Radiography reveals metaphyseal bone lucencies and circumferential periosteal bone formation. Therapy is symptomatic and aimed at relieving pain (eg, aspirin), reducing dietary supplementation, and providing supportive fluid care. Panosteitis Panosteitis is a spontaneous, self-limiting disease of young, rapidly growing, large and giant dogs that primarily affects the diaphyses and metaphyses of long bone. The exact etiology is unknown, although genetics (in German Shepherd Dogs), stress, infection, and metabolic or autoimmune causes have been suspected. The pathophysiology of the disease is characterized by intramedullary fat necrosis, excessive osteoid production, and vascular congestion. Endosteal and periosteal bone reactions occur. Clinical signs are acute, cyclical, and involve single or multiple bone(s) in dogs 6-16 mo old. Animals are lame, febrile, inappetent, and have palpable long bone pain. Nutritional Myopathies: Overview The most common and economically important myopathies of domestic animals are those due to deficiency selenium vitamin E, or both. Characteristically, these are acute diseases and most often, but not exclusively, affect young animals of suckling age. The clinical signs vary widely, depending on the distribution and severity of muscle damage. Frequently, they include stiffness or inability to stand as a result of symmetrical damage to the girdle muscles or the large muscles of the limbs. Complications, such as bronchopneumonia or inability to nurse, may lead to prostration and death within a few days to ~1 wk after onset. Acute cardiac failure is often the precipitating cause of death, especially in calves.

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The lesions in heart or skeletal musculature are almost always bilaterally symmetrical and vary from diffuse, lightcolored areas to well-defined, white streaks or patches. Most muscles can be involved, but macroscopic lesions are most common in the heart or in the large muscles of the shoulder girdle, back, and thighs; those of the diaphragm and tongue also may be affected. Examples have been described under various names in most domestic and laboratory animals, including muscular dystrophy, white muscle disease, nutritional muscular dystrophy, stiff lamb disease, late-lactation paralysis, white flesh, fish flesh, waxy degeneration, paralytic myoglobinuria, and selenium-responsive myopathy. Pathologic changes in other tissues often occur in association with some of the myopathies. These include liver necrosis, subcutaneous and pulmonary edema with exudation into the body cavities, steatitis, gastric ulceration, pancreatic necrosis, gizzard myopathy, anemia, intestinal lipofuscinosis, testicular degeneration, embryonic death and resorption, and encephalomalacia and other nervous system lesions. Concentrations of muscle creatine are generally decreased, with increased calcium and sodium and decreased potassium. Serum from myopathic animals has decreased levels of selenium and glutathione peroxidase and increased levels of lactic dehydrogenase, AST, and CPK. The urine may contain myoglobin and frequently has an increased creatine:creatinine ratio as a result of increased creatine excretion. Nutritional Myopathy of Calves and Lambs (White muscle disease, Stiff lamb disease, Enzootic muscular dystrophy) A myodegeneration frequently occurs in calves and lambs of dams that received selenium-deficient feed during or before gestation. Etiology: Some myopathies (especially in herbivores) and some of the related conditions listed above have been attributed to a deficiency of vitamin E, which may be caused by large amounts of unsaturated fatty acids and other peroxide-forming substances in the diet. For example, continuous supplementation with cod liver oil has induced cases of vitamin E deficiency. White muscle disease in pastured cattle after spring turnout has been attributed to absorption of the portion of polyunsaturated fatty acids in lush grasses that escapes ruminal hydrogenation. In many cases of nutritional myopathy, selenium deficiency is present. This may be a simple deficiency caused by animals eating forage grown on seleniumdeficient soils, or it may be precipitated by antagonistic effects of various metals (silver, copper, cobalt, cadmium, mercury, tin). High dietary intake of phosphorus has enhanced the severity of the disease and resulted in decreased hepatic selenium content in sheep. Application of sulfur to pasture soils, as elemental sulfur or gypsum, may interfere with uptake of selenium by forage plants and precipitate the disease in grazing ruminants. Some myopathies and related conditions respond only to selenium, some only to vitamin E, others to either. While vitamin E cannot completely satisfy the need for selenium, it can reduce the amount required to protect against exudative diathesis. Clinical Findings: The congenital type of white muscle disease may result in sudden death within 2-3 days of birth, usually with involvement of the myocardium. If the condition is severe enough to prevent nursing, either from dysfunction of the muscles of the legs or the tongue, death may result from starvation. Sometimes, there is profuse diarrhea. In chronic cases, there may be relaxation of the shoulder girdle and splaying of the toes. In progressive cardiac failure, dyspnea results. Signs vary with dietary selenium status and, in some areas, general unthriftiness may be the only sign associated with selenium deficiency. Lesions: Generally, skeletal muscle lesions are bilaterally symmetrical and may affect one or more muscle groups. Grossly, the affected muscle is pale and dry. It usually shows distinct longitudinal striations or a pronounced chalky whiteness due to abnormal calcium deposition, but sometimes the involvement may be diffuse. Microscopically, evidence has been established for sequential changes in damaged muscle progressing from mitochondrial swelling and myofibrillar lysis to either hyaline or granular necrosis. When the heart is involved, Purkinje fibers may be damaged. Pleural, pericardial, and peritoneal effusions with pulmonary congestion and edema are not uncommon. Diagnosis: In lambs, outbreaks of infectious, nonsuppurative arthritis result in a clinical syndrome similar to that of white muscle disease, and sudden deaths from heart failure might be confused with enterotoxemia. In calves, the typical syndrome and lesions are reasonably definitive. In mild cases—and particularly in older animals—diagnosis can be difficult, and laboratory studies (as with lambs) may be necessary. Prevention: To prevent white muscle disease within 4 wk after birth, ewes are given 5 mg and cows 15 mg of selenium, PO or SC, usually as sodium selenite 4 wk before expected parturition. A selenium and vitamin E mixture is advocated in some areas. Other procedures for selenium supplementation include administration of intraruminal selenium pellets, use of

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selenium-fortified salt or mineral mixtures, subcutaneous implantation of selenium pellets, or soil application of selenium at 4 g/acre (10 g/hectare) in fertilizer. Treatment: When simple vitamin E deficiency is apparent, dietary supplementation with α-tocopherol or substances rich in vitamin E should be instituted. Ionophore Toxicity Monensin, lasalocid, salinomycin, maduramicin, and narasin may cause myopathy. Horses are highly susceptible, and reports of toxicity also exist for cattle, sheep, pigs, dogs, chickens, turkeys, and guinea fowl. Toxicity has generally resulted from exposure to undiluted premixes or from mixing errors. Toxicosis may be potentiated by various antibiotics and sulfonamides incorporated into feeds in combination with ionophores. Affected horses and cattle may develop anorexia, cardiac failure with tachycardia, dyspnea, diarrhea, stiffness, muscular weakness, and myoglobinuria. At necropsy, pale areas of myocardial necrosis and pulmonary congestion are usually prominent in horses and cattle. Pigs and sheep tend to have mainly skeletal muscle lesions that appear quite similar grossly and histologically to those of nutritional myopathy. Diagnosis requires history of exposure with development of characteristic clinical and pathologic alterations. Plant Intoxication Degeneration of skeletal and cardiac muscles results when cattle and some other animals, notably goats, consume the fruit or beans of certain plants. Karwinskia humboldtiana (coyotillo) and Cassia spp (sennas) have been incriminated. Azoturia and “Tying-up” or “Cording-up” Syndrome of Horses (Paralytic myoglobinuria, Exertional rhabdomyolysis) Tying-up or cording-up is thought to be a mild form of azoturia and, therefore, to have a similar etiology. The terms are applied mainly to light horses and to heavier breeds, respectively; both are associated with skeletal myopathy. (See also fatigue during exercise , Fatigue During Exercise: Introduction.) Etiology: The cause is unknown. Both entities are usually associated directly with forced exercise after a period of rest during which feed has not been restricted, but the disease has been seen in horses on pasture. The cause seems to relate more to excess total feed energy consumption than specifically to the carbohydrate content of the diet as once believed. Clinical Findings: In both tying-up and azoturia, the first signs are profuse sweating, trembling, and rapid pulse followed by weakness of the hindlimbs, which results in a stiff gait and reluctance to move and, in severe cases, myoglobinuria. In azoturia, the disease quickly progresses to recumbency, often with nervous signs. Increased serum activities of AST and CPK are useful indicators of the extent of muscle damage. Prognosis depends on the extent of muscle damage. It is good for those animals that remain standing and fairly good for those that go down due to loss of use of their hindquarters, providing that they remain quiet and contented and the pulse returns to normal within 24 hr. However, survivors sometimes suffer from lameness and prolonged, or occasionally permanent, muscle atrophy. The prognosis is poor for nervous, restless, recumbent animals that continue to struggle and are not quieted by sedatives or tranquilizers; for those that are forced to continue moving after the signs become apparent; and for those that after 24 hr show progressive inability to roll up on the sternum and retain that position. A weak or irregular pulse is most unfavorable. Lesions: Extensive pale areas of myonecrosis are present, especially in the thigh, pelvic, and loin muscles. Muscles are generally moist and dark, but pale areas of myocardial necrosis may occur, and swollen kidneys with a brown cortex and brown-red streaks in the medulla may be seen. Brown urine reflects myoglobinuria. Histopathology reveals hyaline degeneration, myonecrosis, and myoglobinuric nephrosis. Calcification usually is not a component. Treatment: Good management is important. The animal should be kept as quiet as possible, and attempts should be made to keep it standing. Good nursing care should be provided, and precautions taken to prevent development of decubital ulcers. Nervous, restless animals, or those showing evidence of pain, should be given sedatives such as chloral hydrate or tranquilizers. If conditions result in a period of recumbency, an oily laxative should be given. More severely affected horses should not be moved but instead provided with on-the-spot shelter. They should be rubbed dry and blanketed according to the weather. Selenium and vitamin E injections appear to give favorable results in many cases; however, no evidence of underlying selenium or vitamin E deficiency has been found in affected horses. Osteochondrosis: Introduction Osteochondrosis is a disturbance in endochondral ossification that is sometimes classified as dyschondroplasia. It may involve the separation of the immature articular cartilage from the underlying epiphyseal bone, which sometimes
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dissects completely free and floats loose in the synovial cavity and results in accompanying synovitis, or it may result in the retention of pyramidal cores of physeal cartilage projecting into the metaphysis. Often, these two lesions occur simultaneously in the same bone. The disease occurs during maximal growth when the biomechanical stresses are greatest in the immature skeleton (4-8 mo in dogs, 80-120 lb [36-54 kg] in pigs). It is most common in large and giant breeds of dogs and in rapidly growing pigs, horses ( Osteochondrosis , Osteochondrosis), turkeys, and chickens. Osteochondritis Dissecans In osteochondritis dissecans, a focal area of the immature articular cartilage is retained, and the matrix in the basal area of this region becomes chondromalacic and acellular. The immature articular cartilage separates from the underlying trabecular bone. The chondral fracture extends horizontally and vertically until a flap is formed. Synovial fluid gains entrance to the underlying medullary space and subchondral cysts may form (usually only in larger animals). The flap of immature articular cartilage may break away completely (joint mice), or may reattach by endochondral ossification to the underlying bone, especially in pigs, and result in a wrinkled articular surface. The latter occurs only if the joint is rested or protected, which permits reestablishment of the circulation necessary for endochondral ossification. If the flap is torn free by joint motion, it may be ground into smaller pieces during locomotion and disappear, while the larger plaques may become attached to the synovial membrane, become vascularized, and ossify. The resultant articular defect, in time, fills with fibrocartilage. Etiology: The exact cause is unknown, but it is assumed to be multifactorial. Trauma due to excessive biomechanic stresses in focal areas has been implicated. In pigs, complementary lesions in the immature articular cartilage and the adjacent physeal cartilage are not uncommon. The inheritance of predisposing characteristics (rate of growth, excitability, size of skeleton, muscle mass, etc) is not known. The joint most commonly affected varies among species (eg, shoulder in dogs, elbow in pigs). The stifle (medial or lateral condyle) and hock (caudal aspect of medial trochlea of the talus) also may be involved. Clinical Findings: Osteochondrosis causes an insidious and usually persistent lameness beginning, in dogs, at 4-8 mo of age. Lameness is often unilateral, even though the lesions can be bilateral. Occasionally, several joints are affected. The animal may be stiff after resting, and lameness is aggravated by exercise. Depending on which joint is affected, pain can be elicited by hyperextension or hyperflexion (eg, shoulder joints are most painful on hyperextension). Untreated, the lameness persists and becomes permanent due to secondary osteoarthritis. The joint is crepitant, and muscular atrophy develops in the chronic condition. When the articular cartilage does not fracture, the condition may go undetected; however, the silent lesions may be demonstrated radiographically. Diagnosis: The history, age, breed, sex, and clinical signs provide useful information; however, radiographs are required to substantiate the diagnosis. The shoulder lesion is observed on a lateral radiograph as a flattened irregularity of the central caudal half of the humeral articular surface. Osteochondrosis of the femoral condyles in the dog is observed best from a lateral radiograph in which the condyles are not superimposed. Craniocaudal radiographs of the hock in full extension reveal the characteristic depression of the affected surface. The specific lesions in the elbow and hock are not visible on radiographs until after proliferative osteoarthrosis develops. Treatment: A few animals recover spontaneously with 4-6 wk of rest and restricted exercise. Anti-inflammatory drugs are not indicated because they promote physical activity, and thus aggravate the condition. If surgery of affected shoulder joints is performed soon after diagnosis, the prognosis is good. Joint bodies should be removed and the lesion in the subchondral bone curetted. Lesions involving the stifle, elbow, and hock also should be treated surgically; however, the prognosis for these joints is guarded. Problematic Bovine Sternal Recumbency: Introduction (Downer cow) Because ruminants must retain an upright position to eructate gas, a bovid in lateral recumbency is usually near death. Numerous factors can render a bovid unable to stand but still able to maintain sternal recumbency. These animals are often referred to as downers, and those that move considerably may be called creepers. The large immobile mass of the animal makes examination especially difficult; therefore, the specific cause for the recumbency frequently is elusive. Etiology: Recumbency itself can induce sufficient pressure damage of muscle and nerve tissue to prolong the recumbency, even if the primary cause of recumbency is corrected by treatment (eg, as in the case of hypocalcemia associated with parturient paresis). Because there are no specific anatomic signs of conditions such as hypocalcemia, lesions seen on necropsy are usually secondary to the recumbency itself. These include hemorrhagic muscle due to tearing, ischemic muscle resulting from compression, hip dislocation, and even fractures. Nerve damage is indicated by discoloration and perineural fibrosis at the gross level and by demyelination with axonal loss at the microscopic level.
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Most downer cattle are periparturient dairy cows; the common contributing factors are hypocalcemia, metritis, exhaustion due to calving, calving paralysis, toxic mastitis, and trauma associated with concrete floors. Other associated causes include hypophosphatemia, hypokalemia, and hypomagnesemia. The rarity of hypocalcemia and not calving on concrete lessen the incidence in beef breeds. Lifting of affected cows usually reveals that the hindlimbs are unable to support weight, while the forelimbs commonly appear to be functional. Loss of hindlimb function is due to either calving paralysis or pressure damage to the hindlimb that is under the body during recumbency. Because the forelimbs are held lateral to the sternum, which is weight bearing in sternal recumbency, they are protected from compression damage. Other reasons for hindlimbs to be affected more frequently include vertebral lymphosarcoma and abscess, both of which are most common in the lumbar region. Involuntary sternal recumbency not associated with parturition has numerous causes, including vertebral lymphosarcoma and abscess, traumatic injuries, and the weaver syndrome. Traumatic injuries most often are due to falls on slippery concrete or ice and being caught within a stanchion or other restraining structure. The most common skeletal injury is a dislocated hip joint, but fractures of the femoral head and neck and the pelvis also occur. The weaver syndrome is a genetic defect that seems to be limited to the Brown Swiss breed and usually is not manifest until at least 8 mo of age. There is a gradual onset of ataxia, and necropsy findings are nonspecific. Clinical Findings: Periparturient cows should be evaluated for hypocalcemia, mastitis, and metritis. After lifting, the cow should be lowered and raised slowly to determine its ability to bear weight. Some cows are marginal downers; these cows are not able to rise to a standing position without help but, once in a standing position, they can support themselves for a short time and may fall when they start to move. Such cows have the best prognosis for recovery. Crepitus may be felt if the hip is dislocated. With time, a false joint, which is often weight bearing, may be formed. Treatment: The importance of good nursing care for the downer cow cannot be overstated. The recumbent cow should be removed from concrete immediately and provided a soft, clean, and dry surface with good footing. The so-called manure pack provides good footing but also has negative effects; continual urine and manure soiling of the skin can lead to dermatitis and add to the generalized debilitation. Clean, dry sand at least 25 cm (10 in.) deep provides excellent bedding for a recumbent cow. Urine quickly percolates through the sand and, therefore, will not cause skin problems, and manure is easy to remove. If the manure is removed several times daily, the remaining sand can be reused (only what is discarded with the manure needs to be replaced). Prolonged lying in the same position on a hard surface has caused permanent muscle and nerve damage. Prevention: More important than therapy is prevention. Close attention to dietary calcium and phosphorous levels and dry-matter intake during the dry period will minimize the incidence of parturient paresis. Sarcocystosis: Introduction (Sarcosporidiosis) In sarcocystosis, the endothelium and muscles and other soft tissues are invaded by protozoans of the genus Sarcocystis . As the name implies, Sarcocystis spp form cysts in various intermediate hosts—man, horses, cattle, sheep, goats, pigs, birds, rodents, and reptiles. The cysts vary in size from a few micrometers to several centimeters, depending on the host and species. Etiology, Transmission, and Pathogenesis: Sarcocystis spp normally develop in two-host cycles consisting of an intermediate host (prey) and the final host (predator). About 1 wk after ingesting muscle tissue that contains Sarcocystis cysts (sarcocysts), the final host begins to shed infective sporocysts in the feces; shedding continues for several months. After ingestion of sporocysts by a suitable intermediate host, sporozoites are liberated and initiate development of schizonts in vascular endothelia. Merozoites are liberated from the mature schizonts and produce a second generation of endothelial schizonts. Merozoites from this second generation subsequently invade the muscle fibers and develop into the typical sarcocysts. Initially, sarcocysts contain only a few metrocytes—round, noninfective parasites that give rise to the banana-shaped infective zoites found in mature cysts beginning 2-3 mo after infection. Sarcocysts of some species grow so large that they are easily visible with the unaided eye. The presence of such sarcocysts can cause condemnation of the carcass during meat inspection. Sarcocystis cruzi is probably most important in condemnation of beef cattle for human consumption. However, S hirsuta was primarily responsible for dairy cattle condemnation for visible sarcocysts. Sarcocystis meischeriana is usually the species responsible for sarcocyst condemnation of pork and may affect meat quality. Sarcocysts are easily recovered from esophagus, diaphragm, and heart muscle. Sarcocysts of some species remain microscopic even though tremendous numbers of cysts may be present in the muscles. “Immunization” using small doses of sporocysts appears to prevent development or reduce severity of clinical disease in sheep when challenged with large doses later (premunitive immunity).
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Clinical Findings: Sarcocystis spp . infections are quite prevalent in farm animals; however, there have been few outbreaks of clinical disease. Most animals are asymptomatic, and the parasite is discovered only at slaughter. In cattle severely affected by S cruzi , the signs include fever, anorexia, cachexia, decreased milk yield, diarrhea, muscle spasms, anemia, hyperexcitability, weakness, prostration, and death. Cows infected in the last trimester of pregnancy may abort. After recovery from acute illness, some sheep may lose their wool. Equine protozoal myeloencephalitis (EPM,) is now considered to be caused by Sarcocystis neurona . An experimental DNA probe appears promising as a diagnostic tool. Only asexual stages of this parasite have been found and may be located in neurons and leukocytes of the brain and spinal cord. Horses may also develop a myopathy. Multifocal myositis has been reported and is possibly due to S fayeri . Clinical signs in horses include gait abnormalities such as ataxia, knuckling, and crossing over. Muscle atrophy, which is usually unilateral, is possible. The lesions are typically focal, and brain-stem involvement is common. Depression, weakness, head tilt, and dysphagia are other possible signs. EPM can mimic many neurologic diseases. Control: Livestock become infected by sporocysts from the feces of carnivores. Because most adult cattle, sheep, and many pigs harbor cysts in their muscles, dogs and other carnivores should not be allowed to eat raw meat, offal, or dead animals. Supplies of grain and feed should be kept covered; dogs and cats should not be allowed in buildings used to store feed or house animals. Amprolium (100 mg/kg body wt, s.i.d. for 30 days), fed prophylactically, reduced illness in cattle inoculated with S cruzi . Prophylactic administration of amprolium or salinomycin also protected experimentally infected sheep. Therapeutic treatment of cattle and sheep has been ineffective. Vaccines are not available. Experimental work demonstrated that infected pork could be made safe for consumption by cooking at 70°C for 15 min or by freezing at -4°C for 2 days or -20°C for 1 day.

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Nervous System Basic Sensory and Motor Functions: Groups of neuronal cell bodies in the PNS are called ganglia, while those in the CNS are called nuclei. Nuclei form the CNS gray matter. Groups of axons in the CNS form the white matter and are arranged into tracts. The tracts are usually named after their site of origin and termination (eg, the spinocerebellar tract begins in the spinal cord and ends in the cerebellum). PNS sensory or afferent neurons carry information such as nociception, proprioception, touch, temperature, taste, hearing, equilibrium, vision, and olfaction to the spinal cord or brain stem. CNS sensory neurons carry information to the cerebellum, brain stem, and cerebrum for further interpretation. Important spinal cord and brain-stem sensory tracts include several spinocerebellar, spinothalamic, and spinoreticular tract systems. Reactions to sensory inputs are initiated by efferent or motor neurons in the cerebrum and brain stem called upper motor neurons (UMN). The UMN axons descend to brain-stem and spinal cord segments in tracts named after their site of origination and termination. The UMN of the reticulospinal tracts (from midbrain, pons, and medulla oblongata reticular formation) and the rubrospinal tract (from midbrain) are important for voluntary movements of skeletal muscles in domestic animals. The corticospinal tracts (cell bodies in the cerebral cortex) are most important for voluntary movement in primates. Domestic animals with severe cerebrocortical disease may suffer only transient loss of voluntary movements because the corticospinal tract has limited influence. Motor neurons with cell bodies in the brain stem, and spinal cord gray matter with axons that travel in the PNS cranial and spinal nerves, respectively, are referred to as lower motor neurons (LMN). Injury to either the UMN or LMN will result in paresis or paralysis. Brain-stem and spinal cord reflexes are the phylogenetically oldest responses of the nervous system. When the eyelid is touched, it closes; when the toe is pinched, the limb withdraws before conscious perception intervenes. In a monosynaptic reflex (eg, patellar reflex), only a sensory neuron and lower motor neuron are present. Horner's syndrome (ptosis, miosis, and enophthalmos) is a common finding associated with loss of sympathetic innervation to the eye. Divisions and Effects of Lesions: The PNS consists of 26 or more pairs of spinal nerves that correspond to each spinal cord segment and 12 pairs of cranial nerves that correspond to specific brain and brain-stem segments. The spinal cord is divided into 8 cervical, 13 thoracic, 7 lumbar, 3 sacral, and 5 or more caudal segments. Spinal cord lesions from T2 to L7 produce paresis or paralysis of the pelvic limbs (paraparesis and paraplegia, respectively). Lesions from T2 to L3 cause pelvic limb ataxia, conscious proprioceptive deficits, and paresis and paralysis with normal or exaggerated spinal reflexes (UMN signs). Pelvic limb nociception caudal to the lesion may also be depressed or absent. Spinal cord lesions from L4 to S2 cause pelvic limb ataxia, conscious proprioceptive deficits, and paresis or paralysis with depressed or absent spinal reflexes and muscle tone (LMN signs). Spinal cord lesions from C1 to T2 cause hemiparesis or hemiplegia (paresis or paralysis of the limbs on one side), or quadriparesis. The brain stem is divided from caudal to rostral into four segments: the medulla oblongata (myelencephalon), the pons (metencephalon), the midbrain (mesencephalon), and the thalamus and hypothalamus (diencephalon). Lesions of the medulla oblongata cause conscious proprioceptive deficits and weakness on the same side (ipsilateral) or both sides with normal or hyperactive limb reflexes similar to cervical spinal cord lesions. However, involvement of cranial nerve nuclei IX, X, XI, or XII localizes the lesion to the caudal medulla oblongata. Involvement of cranial nerve nuclei VI, VII, or VIII localizes the lesion to the rostral medulla oblongata. It is rare to have a lesion of the medulla oblongata that does not affect one or more of the cranial nerves as well as sensory and motor tracts. Pontine lesions cause ipsilateral conscious proprioceptive deficits, hemiparesis or quadriparesis with normal or hyperactive limb reflexes, mental depression from involvement of the ascending reticular activating system (ARAS), and cranial nerve V deficits. Caudal midbrain lesions cause ipsilateral conscious proprioceptive deficits and hemiparesis. Rostral midbrain lesions cause contralateral (on the side opposite the lesion) conscious proprioceptive deficits and hemiparesis. Cranial nerve III nucleus involvement is present on the ipsilateral side and localizes the lesion to the midbrain. In large midbrain lesions, the ARAS is affected, and the animal will be stuporous or comatose. If the sympathetic UMN and parasympathetic LMN are both affected in the midbrain, the pupils will be midrange size and unresponsive to light. Diencephalic lesions can be difficult to differentiate from cerebral cortical lesions, because many tracts going to and from the cerebrum pass through the diencephalon. The thalamus, hypothalamus, and subthalamus of the diencephalon have many important structures that alter feeding, drinking, sexual, sleeping, and other behaviors, as well as body temperature regulation. The pituitary gland, which controls many hormonal functions of the body, is connected to the hypothalamus. The ARAS projects through the subthalamus area, in which lesions also produce stupor or coma.

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The cerebellum is part of the metencephalon and is attached to the dorsal surface of the pons and medulla by rostral, middle, and caudal cerebellar peduncles. The cerebellum coordinates all muscle activity and establishes muscle tone. The flocculonodular lobe of the cerebellum has equilibrium functions. Unilateral lesions of the cerebellum cause ipsilateral dysmetria (hypermetria or hypometria) and a contralateral head tilt. Bilateral lesions of the cerebellum cause generalized incoordination of the head and limbs, head tremors, and generalized disequilibrium. The telencephalon, also called the cerebral cortex, is divided into the neocortex, paleocortex, and archicortex. The paleocortex and archicortex include the olfactory and limbic regions, which provide smell and emotional reactions to all stimuli. The neocortex is divided into the frontal, parietal, occipital, and temporal lobes. The frontal cortex functions include intelligence and fine motor skills (corticospinal tract). Lesions in this area cause dementia, lack of recognition of the owner, difficulty in training, compulsive pacing, circling toward the lesion (adversion syndrome), and motor seizures with contralateral involuntary muscle twitching. Contralateral hopping and placing deficits are also found with frontal lobe lesions. Ascending and descending tracts to and from the frontal lobe form the internal capsule through the region of the basal nuclei and diencephalon. Lesions of the internal capsule can produce the same signs as frontal lobe lesions. Because few neurologic signs are associated with parietal lobe lesions in animals, cerebral biopsies may be obtained from this site. Occipital lobe and optic radiation lesions result in blindness with pupils that respond normally to light. Unilateral occipital lobe and optic radiation lesions result in some degree of visual loss in the contralateral eye depending on the percentage of crossover of the optic nerve fibers in the optic chiasm of the species (65% in cats; 75% in dogs; 80-90% in cattle, horses, pigs, and sheep). The pupils still respond normally to light. Blindness with pupils that do not respond to light is associated with lesions of the retina, optic nerve, optic chiasm, and rostral optic tract. Difficulty in localizing sound may occur with temporal lobe lesions, as may psychomotor seizures characterized by hysterical running. “Fly-biting” hallucinations are suspected to occur with lesions in the temporal-occipital region. Aggression occurs when lesions of the pyriform area (paleocortex) of the temporal lobe and the underlying amygdaloid nucleus are affected. Aggression can also occur with hypothalamic lesions as well. Lesions of the olfactory region may alter feeding or sexual behavior. Mechanisms of Disease: Degeneration of intervertebral discs that subsequently herniate into the vertebral canal often produces paresis and paralys