Healing

Peritoneal regeneration is completed within 5 to 7 days, regardless of the defect size. Healing can occur by reperitonealization or creation of an adhesion with an adjacent nearby mesothelial surface. This adherent type of healing occurs more frequently if the inflammation is severe, with presence of bacteria and/or foreign material.^620,621,624

Host Defenses Against Peritoneal Infection

The first mechanism of defense is physical removal of the bacteria. In normal dogs, for example, it is possible to retrieve bacteria in the bloodstream 12 minutes after an experimental injection into the peritoneum.⁶²⁴ The second mechanism of defense relates to the response to noxious stimuli. This intense acute inflammatory response includes degranulation of peritoneal mast cells with release of vasoactive substances. This creates a net influx of fluid rich in complement and serum opsonins that can bind to the bacteria.^620,621,624 Third, the omentum contributes to the defense mechanism by adhering to an infected and/or damaged area to wall off the problem site. Finally the rapid movement of neutrophils, and later, macrophages, is also an important mechanism of control of infection.⁶²⁴

Adhesions

Adhesions are defined as fibrinous or fibrous bands that create an abnormal attachment of two or more surfaces that should be moving freely against each other. Formation of adhesions is part of the healing process and should be interpreted as an effort to control an injury. The omentum is often involved in adhesions and acts as a natural sealing device to control the acute phase of inflammation. Whole blood potentiates adhesion formation by providing more fibrinogen.⁶²⁰ The various suture materials are approximately equal in their capacity to induce adhesions, with chromic gut perhaps inducing the most reaction.⁶²⁰ Adhesion may or may not be reversible, depending on the amount of organization that takes place in the process. Adhesions that are cut or broken usually rapidly reform. As the fibrin deposition process is replaced by capillaries and fibroblasts, the adhesion becomes solid fibrous tissue. The three major elements responsible for dissolution of the fibrinous adhesions are (1) adequate oxygen and nutrient supply for the mesothelium, (2) liberation of plasminogen-activating substance by mesothelial and submesothelial cells, and (3) control of the inflammatory process.^620,621 Mechanical obstruction to the normal flow of ingesta and subsequent development of bowel obstruction are major undesirable side effects of formation of adhesions.

Definition and Etiology

Peritonitis is an inflammatory process involving the peritoneal cavity and its serosal surface, the peritoneum. Peritonitis is not a true synonym of intraabdominal infection because the latter is defined as an inflammatory response of the peritoneum to microorganisms and their toxins that results in purulent exudates in the abdominal cavity. Peritonitis should be considered as the localized equivalent of SIRS, whereas intraabdominal infection is the localized equivalent of sepsis. Intraabdominal abscess is an intraabdominal infection confined within the abdominal cavity. Because most often in farm animals peritonitis is caused by bacteria, the two terms are often used as synonyms. The inflammation may result from trauma, surgery, or vascular damage associated with an intestinal obstruction and/or accident or from gastrointestinal ulceration (Box 32-8). Peritonitis is a serious and complex process that is often accompanied by various degrees of abdominal pain, progressive signs of hypovolemia and septicemia, and/or endotoxemia.

Classification

Peritonitis may be classified according to the clinical presentation and/or the cause. Clinically relevant classifications include acute versus chronic, septic versus chemical, localized versus generalized, and primary versus secondary. Although it is useful to classify types of peritonitis, it is imperative to recognize that it is a dynamic process. An apparently localized nonseptic peritonitis can evolve toward a more diffuse septic process if the primary cause is not resolved.

Pathophysiology

After peritoneal injury or contamination, mesothelial cells initiate an inflammatory response, modifying the permeability of the peritoneum and its vascular supply. Several blood constituents are then able to move into the peritoneal cavity. Macrophages and polymorphonuclear cells, humoral opsonins, natural antibodies, serum complement, and a protein-rich fluid are the most important. The inflamed peritoneum also becomes more permeable to toxins, allowing them to be absorbed into the bloodstream. Although this initial response is beneficial to the organism, it induces several systemic abnormalities that the clinician must recognize and treat adequately.

Hypovolemia, hypoproteinemia, bacteremia or septicemia, and toxemia are commonly observed in acute diffuse septic peritonitis. The major adverse effects of peritoneal contamination are (1) rapid clearance of bacteria, producing endotoxemia and/or bacteremia, (2) rapid influx of fluid rich in protein, leading to hypovolemia and hypoproteinemia, (3) deposition of fibrin, occluding lymphatic drainage, contributing to abdominal distention, and enhancing the chance of abscess formation, (4) ileus, and (5) adhesion formation, which may lead to obstruction (Fig. 32-99).

Fig. 32-99 Pathophysiology of peritonitis.

Clinical Signs and Diagnosis

Clinical signs are often nonspecific but suggestive of gastrointestinal dysfunction. Severity of clinical signs ranges from mild recurrent discomfort caused by a localized abscess to an acute severe onset of toxemia and hypovolemia leading rapidly to death after the sudden rupture of a viscus. Cattle suffering from acute peritonitis tend to show more characteristic signs. As the condition becomes less acute, the ability of the bovine to seal the infection will attenuate the clinical signs. Chronic but active peritonitis remains to this day a very difficult diagnosis to make without ancillary tests. Abdominal rigidity and tenderness, abdominal distention, scleral injection, fever, anorexia, and sudden reduction in milk production are classic but not pathognomonic findings of acute peritonitis. In the acute stage, abdominal pain and the release of catecholamines often lead to a complete gastrointestinal stasis and ileus. The rumen is then completely atonic. Feces are abnormal in quantity and quality. In the acute stage, feces are present in small amounts and often dry. In more chronic cases feces are present with a tendency to be diarrheic. Pain, decreased plasma volume, and endotoxemia often result in persistent tachycardia. Anterior abdominal pain, evaluated by the withers pinch test, may be difficult to interpret. This procedure is based on the normal reflex of the bovine to drop its back when the withers and back are pinched (ventroflexion). Cattle with anterior abdominal pain may be reluctant to ventroflex on withers pinch. You can increase the sensitivity of this test by simultaneous auscultation of the trachea during the manipulation. Production of an expiratory grunt is considered as a sign of pain during ventroflexion. Cranial ventral pressure with the fist, knee, or some other external force (transverse pole under the abdomen) just behind the xiphoid can help identify the presence of pain (expiratory grunt) and even localize it in some cases. It is my impression that one of the most reliable clinical sign of abdominal discomfort in cattle is reluctance to move. Scleral injection, fever, tachycardia, gastrointestinal stasis, and distention are the clinical signs that should be monitored to evaluate peritonitis.

Ancillary Tests

Hematologic findings associated with peritonitis range from a completely normal hemogram to severe leukopenia with degenerative left shift and presence of toxic neutrophils, depending on the severity of the peritoneal contamination. In severe cases variations observed reflect the degree of sepsis and toxemia. PCV tends to increase as proteins decrease. In less severe cases, a neutrophilic leukocytosis and hyperfibrinogenemia are often present. Hematologic analysis has been a useful tool to monitor response to therapy after a diagnosis has been made by other ancillary tests. Immature cells in the peripheral blood and/or leukocytosis were better indicators of recurrence than body temperature in one human study.⁶³¹ Plasma fibrinogen concentration is also used to monitor the progress of a particular case.

The blood chemistry profile is rarely altered by peritonitis in a way that is diagnostically useful. Chronic inflammation causes a marked increase in serum proteins, particularly the globulin portion. In acute severe cases, secondary findings may include increased serum urea nitrogen and creatinine, mildly increased liver enzymes, reduction in total CO₂, and strong ion difference and reduction in serum albumin. Ileus and upper gastrointestinal stasis may result in marked hypochloremia and alkalosis.

Cytologic examination of the peritoneal fluid is a useful aid in making a definitive diagnosis of peritonitis (see Table 32-17).⁶³² Abdominocentesis techniques have been described elsewhere.⁶³⁰ The right side just cranial to the udder is the preferred site (to avoid stomach and omentum) (Fig. 32-100). A needle, a blunt teat canula, or a bitch catheter and scalpel blade may be used with success (Fig. 32-101). The heavy fascia of bulls makes a needle preferable. It is imperative to remember that failure to secure fluid is common and should be interpreted with caution (because fibrinous peritonitis with fluid loculation is common). More than one site should be attempted if no fluid is secured on the first attempt. Interpretation and classification of peritoneal fluid analyses have been reviewed by several authors.^{622,626,627,630} After exploratory celiotomy and omentopexy on normal cattle, peritoneal fluid has increased specific gravity, total protein, and WBCs for at least 6 days, even without any peritonitis.⁶³³ One should remember that because of the bovine’s ability to deposit fibrin and seal areas of the peritoneal cavity, the interpretation of peritoneal fluid analysis applies only to the immediate area that was sampled. The clinician can be misled to conclude that a nonseptic process is occurring on the basis of a caudal tap, when in fact a septic process has already been sealed by the fibrin deposition in the cranial abdomen.

Fig. 32-100 Site of caudal abdominocentesis.

Fig 32-101 Material used to perform abdominocentesis of the bovine.

Abdominal radiographs using a high-power unit are extremely useful in cases in which TRP is suspected.⁶³⁴ They have limited value in other causes of peritonitis. A review of radiography of the bovine cranioventral abdomen is available.⁶³⁵

Ultrasound examination is useful for assessing the size and anatomic relationships of lesions, particularly when considering drainage, aspiration, or surgical exploration of a mass surrounding vital structures. The reader should see the section on ultrasound in this chapter. Knowledge of the underlying anatomy is important to prevent misinterpretation. Clarity of the image is affected by the size of the probe and the depth of tissue being evaluated. Higher-frequency probes produce finer images but have limited tissue penetration. Images reflect the echogenicity of the tissues viewed; relative echogenicity helps to differentiate structures. Abscesses can have mixed echogenicity, varying from anechoic (absence of internal echoes) to echogenic, depending on the relative amount of fluid, fibrin, and gas. The fibrous capsule of abscesses may be identified as echogenic bands around the area in question. Ultrasound is particularly useful for evaluating the integrity of the body wall for presence of hernias resulting from traumatic injuries, secondary to abscessation or incision dehiscence. Normal and abnormal appearances of umbilical structures have been described.^636,637 Recognition of free abdominal fluid is easily accomplished by ultrasound examination, and it is also useful to guide a peritoneal tap. Areas that should be scanned include the caudal lower flank area (right and left), right perirenal area, liver, abomasum and pylorus, and right paramedian area. Normal liver and liver abscess formation have been described.^638,639 References are available to describe normal appearance of the reticulum and the small intestine in cows.^640,641 During exploratory surgery, ultrasound can be used to image an internal mass or a viscera appearing abnormal. Intraoperative ultrasound is performed by placing the probe in a sterile sleeve filled with ultrasound gel.

Surgical exploration is often used to confirm or rule out an intraabdominal problem.⁶⁴² Information obtained from physical examination and laboratory data is often indicative of a diagnosis but does not provide a specific cause. Cattle are particularly amenable to exploratory surgery, as the procedure is performed when they are standing and is not often associated with complications. Recent advances in minimally invasive surgical technique in cattle are promising. Laparoscopy can be used to diagnose acute and chronic peritonitis, which is otherwise difficult to identify with ultrasound or abdominocentesis. It is easier to evaluate the extent of the lesions with the organs in situ.⁶⁴³

Treatment

The basic elements of therapy are support, antibiotics, and surgery.

Ascites

Ascites is a collection of serous fluid in the peritoneal cavity. It must be considered as a secondary sign rather than a primary diagnosis.⁶⁴⁹ In that regard the primary cause must be identified in order to treat the patient adequately. Common causes of ascites in ruminants include severe liver disease and congestive right-sided heart failure. Young cattle with mesothelioma have remarkable ascites. Ascites remains an uncommon condition that needs to be differentiated from septic causes of peritonitis and from urine accumulation with ruptured bladder.

Pneumoperitoneum

Pneumoperitoneum is commonly observed postsurgically in the bovine. Presence of air in the abdomen can be recognized by simultaneous percussion and auscultation. A low-pitch resonance can be auscultated in the upper flank on both sides of the abdomen. Presence of pneumoperitoneum normally resolves in the week after surgery. No clinical signs seem associated with the presence of pneumoperitoneum, although some clinicians describe abdominal pain associated with no other cause than the presence of air in the peritoneal cavity. Pneumoperitoneum not associated with surgery is indicative of bacterial peritonitis and the presence of gas-producing bacteria (Box 32-9).

Retroperitoneal Abscess

Retroperitoneal abscess is a particular condition occurring in cattle after a flank laparotomy. Animals are often presented several days after surgery. They are mildly febrile, not performing adequately, and showing clinical signs compatible with peritonitis. The skin wound is often unremarkable, but some pain may be elicited while the flank area is palpated. A substantial mass may be palpated per rectum, localized in the upper quadrant of the side of the previous surgical approach. The mass will be firm, smooth, unmovable, and close to the previous flank incision. Transabdominal or rectal ultrasound examination reveals a large amount of fluid located between the peritoneum and the rectus abdominis or the internal oblique of the abdomen. More superficial abscesses can also occur. A needle aspiration allows visual inspection of a thick, opaque, foul-smelling fluid. Treatment is aimed at establishing drainage and systemic antimicrobial therapy. A large volume of purulent and fibrinous material (up to 40 L) can be removed from the abscess. Rapid decompression may provoke hypovolemic shock, and intravenous fluids should be administered before a large abscess is drained. Prognosis is good, but the recovery phase is extremely long because of the large cavity left after drainage. Early closure of the drain is often observed, necessitating reopening.

Definition and Etiology

Frothy bloat is caused by diets that lead to the formation of stable froth in the rumen. Ruminal tympany is synonymous with bloat. The condition may be fatal if the distention is extreme enough to compromise ventilation by compressing the thoracic viscera. Cattle are more susceptible than sheep, but the disease does occur in the same circumstances in small ruminants.

Clinical Signs and Differential Diagnosis

The degree of forestomach enlargement varies from that producing an even filling of the left paralumbar fossa to that causing a uniform, extreme abdominal enlargement when the animal is viewed from the rear. With intermediate degrees of distention, the left paralumbar fossa bulges beyond the contours of the last rib and the tuber coxae. Clinical signs of colic may be seen, including kicking at the abdomen, treading, frequent lying down and rising, and vocalizations. Some animals adopt a stretched stance with the rear feet placed far back. Sheep with heavy fleece may be significantly bloated without the changes in abdominal contour being obvious. As the forestomach enlarges and compresses the diaphragm, breathing becomes more labored. Open-mouth breathing, cyanosis of mucous membranes, and collapse leading to death may occur within a few minutes if the animal becomes frantic from the abdominal pain and dyspnea. Other conditions to consider in the diagnosis of frothy bloat in ruminants include other causes of ruminal enlargement: free gas bloat and vagal indigestion. Advanced pregnancy, hydropic conditions of the uterus, left or right abomasal displacements, cecal dilation or volvulus, intestinal volvulus, omasal bursitis, ascites, diffuse peritonitis, and pneumoperitoneum are conditions creating abdominal enlargement that may be included in the differential diagnosis.

Many systemic conditions influence the motility of the forestomach and thus may produce mild bloat coincidentally.

Clinical Pathology

Clinical pathologic measurements are not required for the diagnosis and management of most cases of frothy bloat in ruminants. When no cause for forestomach enlargement is obvious, evaluation of a sample of ruminal contents may provide information useful for prescribing treatment and prevention. The presence or absence of froth and the pH are critical features relating to the cause that influence the choice of therapy. The normal pH of the rumen varies with time after feeding but should be between 5.4 and 6.8.

Pathophysiology

Regardless of the cause of forestomach distention, the process may become self-perpetuating because of reflex inhibition of motility. Low-threshold stretch receptors in the ruminal wall augment cyclic forestomach contractions when stimulated. However, stimulation of high-threshold stretch receptors leads to inhibition of motility. Thus, beyond a certain degree of stretching of the ruminal wall, further contractions that may relieve the distention through eructation are prevented.⁶⁵⁰

Frothy bloat is caused by the retention of gases of fermentation within the mass of ingesta that fail to rise and coalesce into a dorsal gaseous layer. This condition can arise from diets of lush legumes or winter wheat pasture or may be seen with high-concentrate finishing rations in the feedlot. In the case of legume-induced disease, bloat has occurred after grazing or feeding of fresh-cut forages or the feeding of alfalfa hay. The structure of stable froth in the affected ruminal contents is not a true foam. The ingesta in the septa between adjacent bubbles form a complex structure that prevents coalescence. The viscosity of the fluid may prevent gravitational flow through the septa that would lead to the bubbles’ rising and coalescing. Frothy ruminal fluid is higher in chloroplast membrane fragments, soluble protein, and very fine particles than nonfrothy ruminal fluid.⁶⁵¹ The presence of the resulting frothy ingesta at neural receptors believed to be near the cardia prevents the reflex relaxation of the cardia during the secondary contractions of the forestomach that ordinarily lead to eructation.⁶⁵² In addition, the viscosity of the frothy ingesta is such that the cardia may become plugged during attempts to eructate.

Current research⁶⁵¹ supports both animal and plant characteristics as predisposing to legume bloat. Individual cattle have been classified as having either high or low susceptibility to legume bloat. Thus far, highly susceptible cattle have been shown to have larger ruminal volumes and specific salivary proteins in consistently different proportions than bloat-resistant cattle. The actual mechanisms that lead to larger forestomach volume in susceptible cattle have not been determined. There is a relationship between plant factors associated with bloat and the rapidity with which leaf structure is disrupted after ingestion.⁶⁵¹ Bloat-inducing plants are more readily macerated, thus providing quicker bacterial access to the inner leaf cells. Less bloat-predisposing cultivars of the main bloat-causing species, such as alfalfa (Medicago sativa), red clover (Trifolium pratense), and white clover (Trifolium repens), have a thicker leaf cuticle, smaller stomata, and a more fibrous leaf structure. Ionophore antibiotics such as monensin inhibit ruminal protozoa that normally ingest chloroplasts, leading to a reduction in the bloat potential of some forages.^653,654

Grain bloat occurs in a manner similar to that caused by legumes; a stable froth is produced from high-concentrate rations. Particle size and the rate of fermentation are thought to be the determining factors in the froth production. A mucoprotein slime composed of bacterial byproducts stabilizes the froth.^653,655 This material tends to be stable at a lower pH than is found in non—grain-fed ruminants, so grain feeding promotes slime accumulation by lowering ruminal pH. Genetically susceptible cattle lack adequate mucin in their saliva to disrupt the tiny gas bubbles. Animals (such as dairy cattle) that are fed grain and then legumes may be particularly susceptible to frothy bloat because all the factors leading to froth production and accumulation are present. Both legume bloat and grain bloat may resolve spontaneously if the animal stops consuming the bloat-producing feed and microbial digestion eliminates the froth-stabilizing factors.

Acute distress, often appearing as colic, is caused by overdistention of the forestomach that stimulates pain receptors in the ruminal wall. As the abdominal distention increases, the ability to achieve normal respiratory movements of the diaphragm and rib cage is impaired. Death from asphyxia ultimately results as the lungs are compressed by the cranially expanding diaphragm.

Epidemiology

Frothy bloat often occurs as an epidemic. Pasture bloat occurs wherever alfalfa, red clover, or white clover is grazed. Environmental conditions that produce rapid, early growth lead to a higher incidence of bloat. Frothy bloat also occurs when stocker cattle are grazed on winter wheat pastures in the southern Great Plains of the United States. Death losses at pasture range from 0.5% to 2.5% of cattle at risk on an annual basis. The incidence of feedlot bloat has been estimated at about 1%, with death losses of about 0.1%.⁶⁵¹

Necropsy Findings

The finding of tenacious froth in the rumen along with other evidence of bloat is grounds for a presumptive diagnosis of frothy bloat. The challenge for the diagnostician is to determine if the bloat occurred before death; this may not be possible if the animal was not observed before death. The increase in intraabdominal pressure prevents venous return from the hindquarters and may lead to obvious edema in the intermuscular areas. Unfortunately this is not a consistent finding; other evidence of impaired circulation or a differential degree of edema between fore and hind parts must be used to make a diagnosis.

Treatment and Prognosis

Passage of a stomach tube is indicated to determine the cause of the ruminal distention and possibly initiate treatment. A sample of the ruminal contents for pH measurement should be obtained at this time. Care must be taken to exclude saliva from the tube by blowing into the rumen, flushing water through the tube, or using a ruminal sampling device that carries the tip of the stomach tube down into the liquid ingesta. If no gas can be released with a stomach tube, the tube should be withdrawn after suction has been applied and examined for the presence of froth. If the animal is not in respiratory distress or extremely colicky, surface-active agents should be administered by means of a stomach tube. Poloxalene is recommended for forage bloat,⁶⁵⁴ and mineral oil or animal tallow for feedlot bloat.⁶⁵⁷

Some cattle are in violent pain with bloat but not in respiratory distress. Sedation with xylazine may be necessary for further examination and treatment. Animals with extreme distention of the forestomach and in respiratory distress require immediate surgical intervention. A trocar introduced through the left paralumbar fossa after local anesthesia relieves bloat caused by free gas accumulation but may not be adequate for frothy bloat. An emergency rumenotomy may be necessary to evacuate frothy contents.

Prevention and Control

Prevention of frothy pasture bloat has historically relied on attempts to anticipate when forages were most likely to induce bloat. Cattle were fed other feeds and allowed limited access to the problem forages. Accurately predicting when forages are safe has not been reliable. As an alternative the cattle at risk have been treated with supplemental surface-active agents such as poloxalene.

In Australia and New Zealand, oils and tallows have been drenched daily, sprayed on fields, and smeared on the flanks to be later licked off, to prevent pasture bloat. Although poloxalene has proved effective, it is more expensive than oils. It can be fed in molasses blocks or individually administered. More recently ionophore antibiotics have shown promise for controlling bloat. Rumensin (1 mg/kg daily) greatly reduced the incidence of legume bloat, and lasalocid (1.32 mg/kg/daily) effectively reduced the incidence of grain bloat.^653,654 In both circumstances, beginning treatment before exposure to the bloat-inducing feed was more effective than waiting until bloat occurred. Agronomists are selecting cultivars of the bloat-producing forages for slower rates of initial fermentation. These are likely to become more widely used in the regions in which bloat is a regular occurrence.

Providing adequate fiber in feedlot rations and slowly introducing higher proportions of concentrates, particularly corn, barley, and soybean meal, permit ruminal adaptation that helps prevent bloat.

Etiology

Although the precise cause of displacement of the abomasum remains unknown, general agreement exists in veterinary literature that it is a multifactorial syndrome and that abomasal hypomotility is an absolute prerequisite. Abomasal motility can be decreased in many ways. Overdistention of the rumen, reticulum, or omasum can inhibit motility of the abomasum,⁶⁵⁸ as can ulcers and ostertagiasis.⁶⁵⁹

Many of these conditions occur commonly in the immediate postpartum period or are related to common disorders of postpartum dairy cattle (Table 32-18).

Table 32-18 Factors Associated with Influencing Abomasal Motility and Contributing or Possibly Contributing to Abomasal Displacements

Prevalence and Incidence

Abomasal displacement occurs either to the right or to the left side of the abdomen when gas accumulates within this viscus. Left-displaced abomasum (LDA) is the more common, accounting for 85% to 95.8% of cases.⁶⁸⁰ By far the highest incidence is in adult dairy cattle in the early postpartum period, but cases have been seen in all other classes of cattle. LDA is probably a worldwide problem, and one survey of the prevalence of disease in dairy herds indicates that 24% of herds reported at least one case of LDA during a 3-year period.⁶⁶² In one Canadian study the lactational incidence risk of LDA was estimated to be 2%.⁶⁸¹ The prevalence among dairy herds is variable depending on geographic location, management practices (confinement vs. pasture), feeding practices, climate, and probably several other factors.

Pathophysiology

After abomasal atony, distention with gas produced by microbial fermentation occurs and most likely precipitates the displacement. Diets with more grain result in an increase in the amount of gas produced in the abomasum. It has been hypothesized that the displacement will be oriented (left or right) according to the size of the rumen. A large and filled rumen will make the left displacement less likely, and the abomasum will dilate and in some cases twist to the right (Figs. 32-102, 32-103, and 32-104). If the rumen is small and empty (as in the postpartum period), the abomasum can move to the left and LDA can occur.⁶⁶⁴

Fig. 32-102 Schematic view of a left-displaced abomasum.

Courtesy André Desrochers, from Surgery of the abomasum in cattle, Version 2.0, Université de Montréal.

Fig. 32-103 Schematic view of a right-dilated abomasum.

Courtesy André Desrochers, from Surgery of the abomasum in cattle, Version 2.0, Université de Montréal.

Fig. 32-104 Schematic view of an abomasal volvulus (AV).

Courtesy André Desrochers, from Surgery of the abomasum in cattle, Version 2.0, Université de Montréal.

Surgical Therapy

Numerous surgical techniques are used and have been described elsewhere.⁶⁸⁰ The comparison of their advantages and disadvantages has also been studied.⁶⁸² The permanent attachment is usually created by suturing either the abomasum or the greater omentum to the abdominal wall. The techniques may be classified into three different broad categories: blind technique, surgical (open) technique, and laparoscopic technique. Multiple factors influence the decision; cost and preference of the surgeon are very important. Recently, laparoscopic technique has been described and studied.^683-686

All techniques have been successful when performed adequately. Understanding the limitations of each of them will allow the food animal clinician to best serve the patient and client in all situations.

Clinical Signs and Differential Diagnosis

Cattle with simple LDA have a reduced appetite (complete anorexia, reduced consumption of concentrates, or alternating periods of normal appetite and anorexia). Milk production is reduced. Ketosis may develop as a secondary problem. Feces are often normal to softer than normal but reduced in volume. Rectal temperature is normal, unless a concurrent infectious problem is present (metritis, mastitis). Pulse and respiration are normal or slightly above normal, unless a concurrent or secondary problem is present. Ruminal contractions are decreased to absent and difficult to hear because the abomasum interferes with transmission of the sound. The last one or two ribs on the left are sprung, but the abdomen is sunken in the paralumbar fossa. Gurgling or tinkling rather than normal scratching sounds may be heard on auscultation in the left paralumbar fossa. Simultaneous auscultation and percussion reveal a ping over the gas-filled portion of the abomasum (see Fig. 1-5). With LDA the area of ping may be anywhere from the lower third of the abdomen in the eighth intercostal space to the paralumbar fossa. Attention should also be given to the cranial and lower aspect of the flank because in some cases the ping will be audible only in this area.

On rare occasions, during rectal examination the clinician may be able to palpate the abomasum to the left of the caudodorsal blind sac of the rumen or at least perceive that the rumen is displaced medially.

Ruminal tympany, pneumoperitoneum, and collapsed rumen⁶⁸⁷ may all produce pings on the left side of the cow. Physometra (air in the uterus) and dilation and displacement of the cecum to the left of the rumen (which is rare) may also produce left-sided pings. Having an assistant blow on the stomach tube passed into the rumen while auscultating over the left side differentiates the rumen from other structures. Percutaneous needle aspiration of fluid or gas from the suspected abomasum aids in correct identification. A pH of less than 4.5 as determined with wide-range pH paper or the odor of abomasal gas (slightly acrid or burnt almonds) confirms the presence of LDA.

Clinical Pathology

The most important abnormalities detected by clinical chemical evaluation usually are the serum electrolyte and acid-base levels.⁶⁸⁸ Sequestration of the hydrochloric acid secreted into the abomasum within the abomasum or by means of reflux in the ruminoreticulum may occur and lead to metabolic alkalosis. The blood pH and bicarbonate concentration are slightly elevated, with a concomitant small decrease in the blood chloride concentration. Cattle examined on the farm usually are hypoglycemic and ketonuric. However, any important stress (e.g., transportation) may create a transient hyperglycemia. The serum calcium level may be below normal as a result of decreased intake and absorption. Hypokalemia may develop as a consequence of both the metabolic alkalosis and reduced intake and absorption.

The CBC may reveal a mild dehydration and a stress leukogram. If LDA is combined with bleeding abomasal ulcers it may produce severe anemia. The presence of a concurrent disease may lead to specific changes (e.g., left shift with acute coliform mastitis).

Epidemiology

Cows in early lactation are at greatest risk of developing LDA. In one prospective study of 3172 lactations in New York, 81% of 48 LDAs occurred in the first 30 days after calving.⁶⁸⁹ The overall incidence was 1.5% of lactations. An older study reported a lower incidence rate (0.35% from 1970 to 1972), but even within that period the rate increased each year.⁶⁹⁰ A higher incidence has been reported in late winter and early spring after the winter housing season.⁶⁹¹ Cows in this study had LDA in association with parturition as expected, but a preponderance of cases occurred in cows calving in February to April. Increasing parity was associated with an increased incidence of LDA in studies from Ontario, Canada, New York, and Israel.^690-692 Milk production potential is not thought to be related to the risk of LDA.⁶⁹³ Most cows produce 300 to 500 kg less milk in lactations with LDA than would be expected if the disease did not occur.⁶⁹⁴ For unknown reasons, about 80% of recovered cases produce about 400 kg less milk, and 20% produce 2000 kg less milk. Length of time a cow remains in the herd after correction of LDA is not affected. The financial consequences of LDA for an individual cow with the smaller reduction in milk production favor maintaining the cow in the herd.

Energy and protein nutrition of the prepartum dry cow were suggested to be causally related to LDA in one study.⁶⁹⁵ On a herd basis, in cows fed levels of energy and protein above National Research Council recommendations, LDA was less likely to develop. Genetic factors may also play a role in the predisposition to LDA. In a retrospective case-control study, cows with LDA were 1½ times more likely to be sired by bulls in one group than controls.⁶⁹¹ Fox⁶⁹⁶ suggested that body depth had increased in dairy cattle since 1945 and that this may provide more room for the relatively empty abdominal viscera to move about at parturition. An experimental herd composed of two groups of Holstein cows, continuously mated and selected to produce large and small body sizes, had a 4.5% incidence of LDA in the large size group and a 1% incidence in the small cows during a 14-year period.⁶⁹⁷ Body weight was 514 kg versus 464 kg, wither height was 134 cm versus 129 cm, and fat-corrected milk production was 6163 kg versus 6135 kg for the two groups. Thus some evidence exists to support a genetic basis for predisposition to LDA, and perhaps this is mediated through body size or conformation.

Treatment and Prognosis

Treatment for LDA involves returning the abomasum to its normal anatomic location and preventing reoccurrence (“pexy”), treating the electrolyte and acid-base abnormalities, and providing therapy for concurrent disease conditions. Prognosis for LDA is good but is influenced by the severity of the concurrent disease. Cattle with severe hepatic lipidosis and LDA should be given a guarded prognosis, as their recovery is often slow and incomplete.

Prevention and Control

The incidence of LDA has been reduced in problem herds by dietary manipulation that reduces the likelihood of forestomach and abomasal atony caused by high-concentrate rations. This includes slow introduction of concentrates after calving, prepartum introduction of ensiled and concentrate feeds and increase in the particle size of the forage. Maintaining serum calcium concentration around parturition may be achieved by dietary management during the prepartum period. Dietary cation-anion difference (DCAD) is a reliable method of controlling hypocalcemia in dairy cows (see Chapter 41). Reduction in other periparturient inflammatory diseases such as mastitis and metritis also reduces the incidence of LDA.

Clinical Signs and Differential Diagnosis

The general systemic state of the cow with a simple RDA is the same as that of the cow with LDA. On the other hand, as the simple RDA evolves toward the volvulus, the systemic changes observed in cattle with abomasal volvulus progressively appear. An area of tympanitic resonance is heard on the right side with simultaneous auscultation and percussion. The ping usually is confined to an area under the last five ribs in the upper half of the abdomen. The condition must be differentiated from other causes of right-sided pings, such as cecal distention (with or without volvulus), gas in the spiral colon, pneumorectum after rectal examination, pneumoperitoneum, physometra (gas in the uterus), and abomasal volvulus (see Fig. 1-4).^699,700 Cecal and rectal pings usually are detectable in a linear pattern just below the transverse processes of the lumbar vertebrae extending to the tuber coxae. Rectal examination identifies the gas-filled structure. Pings heard with gas in the spiral colon typically have a variable pitch, depending on the location over the cranial paralumbar fossa and last three or four ribs. Generally the spiral colon may be palpated per rectum as a laterally flattened, mildly distended viscus adjacent to the right body wall. Gas in the uterus can be detected per rectum. Pneumoperitoneum creates a ping that is distributed all along the dorsal portion of the abdominal cavity and is usually heard on both sides.

Abomasal volvulus is the most difficult to differentiate from RDA. Determination of the difference by physical diagnosis in an early case of abomasal volvulus is probably impossible. With time the cow becomes progressively more dehydrated and more severely ill with volvulus than is usual with RDA. Heart rate (above 100 beats/min), ruminal motility (totally absent), and fecal output (almost none) are clinical signs in favor of a diagnosis of abomasal volvulus. Advanced cases of volvulus also have a ping that has an arched dorsal border and a horizontal ventral border caused by the fluid level in the abomasum. This fluid is auscultable on succussion of the abomasum.

Treatment and Prognosis

Surgical treatment is required to correct RDA. Because of the difficulty of differentiating RDA from early volvulus, intervention should be as prompt as possible. The prognosis for a successful recovery after surgery is comparable to that for LDA if no other concurrent disease is present.

Clinical Signs and Differential Diagnosis

The systemic effects of the gastrointestinal obstruction that results from abomasal volvulus progress to a much more severe degree than in LDA or RDA. Sunken eyes and loss of skin turgor accompany the dehydration that develops. The heart rate increases above 100 beats/min, and the pulse is weak and thready. Abdominal distention is marked bilaterally. Complete ruminal stasis develops, leading to bloat, and the abomasum greatly enlarges on the right. Despite the severe degree of gastric distention, colic rarely develops in abomasal volvulus; it is much more likely with cecal distention. The skin is cool to the touch. Feces are absent or watery but scant. A large area of tympanitic resonance with uniform pitch throughout is detectable on the right, extending from the eighth rib to the middle of the paralumbar fossa (see Fig. 1-5).⁷⁰⁰ The ventral border of the ping is a horizontal line reflecting the fluid level in the greatly distended abomasum. Borborygmi are absent. Splashing fluid sounds can be heard when the abomasum is ballotted (succussed) behind the last rib.

Other causes of proximal intestinal obstruction and torsion of the intestinal mass around the root of the mesentery must be differentiated from abomasal volvulus. On rectal examination the abomasum can usually be felt with abomasal volvulus. With intestinal obstruction or intestinal volvulus, distended loops of small intestine can be palpated. Pings caused by gas in the intestines have a variable pitch over the area involved.

Cecal distention with rotation can produce a similar degree of abdominal distention high on the right, but the abdomen usually is less filled cranioventrally on the right. A ping extends to the tuber coxae, and the cecum can be palpated per rectum. Diffuse peritonitis leads to complete atony of the gastrointestinal tract, and the abdomen may become distended with gas in all parts of the tract; there is no discrete ping extending over a large area of the right side.

As abomasal volvulus progresses, cattle become recumbent and depressed. Death occurs within hours of this stage, which occurs 1 to 3 days after the development of the volvulus.

Clinical Pathology

The serum biochemistry profile will show much more dramatic changes with abomasal volvulus than with RDA or LDA. Clinicopathologic consequences include hypovolemia, dehydration, hemoconcentration, metabolic alkalosis, hypochloremia, hypokalemia, and paradoxic aciduria. Hyperglycemia, hypocalcemia, and hyponatremia may also be observed. Later in the condition a superimposed metabolic acidosis is also present. Anion gap gradually increases with the severity of the disease. Systemic shock eventually causes fatality. Reduced fluid intake and sequestration of large quantities of chloride-rich fluid in the stomachs (third space problem) leads to dehydration and hypovolemia.

Under the influence of carbonic anhydrase, hydrogen ions are normally pumped into the abomasal lumen. A chloride ion follows into the lumen, whereas bicarbonate and sodium remain in the blood. Under normal circumstances the HCl leaves the pylorus, where the hydrogen ions are neutralized by pancreatic and intestinal secretions and the chloride is resorbed. When abomasal volvulus occurs, the HCl is sequestered in the abomasum and regurgitated into the omasum and rumen (internal vomiting). Ruminal chlorides increase. The animal becomes alkalotic and hypochloremic. Because of shifts between intracellular and extracellular compartments, potassium moves intracellularly as hydrogen ions move extracellularly in response to the metabolic alkalosis. This, plus the total anorexia, lead to severe hypokalemia. The hallmarks of abomasal volvulus are metabolic alkalosis, hypochloremia, and hypokalemia.

Paradoxic aciduria occurs in the face of metabolic alkalosis, when the cow should be retaining hydrogen ions.^701,702 The overwhelming renal physiologic drive appears to be sodium retention. Dehydration and reduced cardiac output result in falling blood pressure. The animal must respond by volume expansion; thus sodium is resorbed in the renal tubules. Chloride is also resorbed. Because there is hypochloremia, the electrical gradient that must be corrected is high; if 140 mEq/L of sodium is resorbed and only 60 mEq/L of chloride is available, there is a net of 80 mEq/L (140 − 60) of cations that must be secreted back into the tubules. This is normally accomplished by secretion of potassium. Because hypokalemia is severe, hydrogen ions are paradoxically secreted to retain electrical neutrality so that blood pressure can be maintained by means of maximum sodium resorption.

Pathophysiology

At least some of the factors predisposing to LDA or RDA probably contribute to the paths of abomasal volvulus. Whether true RDA precedes abomasal volvulus is not known. Dissection of naturally occurring cases of abomasal volvulus demonstrated that the structures involved in rotation can vary from the reticulum to the omasum at the orad end.^698,703,704 The rotation probably occurs most frequently at the reticuloomasal junction. The duodenum is looped around the omasum, regardless of the degree of volvulus. Creating the condition manually in an anesthetized calf was easier if the gas-filled fundus ascended around the cranial surface of the omasum, pulling the reticulum with it.⁷⁰³ The ensuing displacement leads to a counterclockwise rotation of the abomasum and omasum as viewed from the right side and the rear. The duodenum is pulled medial to the body of the omasum and wraps around the neck of the omasum in the final configuration. The continued hydrochloric acid secretion of the abomasum and the gas produced in the omasum and abomasum further stretch and occlude the duodenum. The abomasal blood vessels and the ventral vagal trunk are compromised near the site at which the duodenum wraps around the omasum in long-standing cases. Thrombosis of vessels may occur.

The acid-base and electrolyte abnormalities of early abomasal volvulus are the same as those of LDA. In cases of severe distention of the abomasum and omasum with vascular compromise, systemic cardiovascular insufficiency develops. Reduced perfusion of peripheral tissues may lead to metabolic acidosis terminally. Hemoconcentration develops, although bleeding into the abomasum may occur from devitalized mucosa, leading to a low hematocrit. These changes are compounded by the developing necrosis of the abomasum. The abomasum may physically leak contents through a weakened, overstretched wall. Endogenous inflammatory mediators and bacterial toxins may diffuse from the abomasum to viable surrounding tissues, where absorption occurs. In either case, the viability of the abomasum is lost, and death follows shortly.

Treatment

Immediate surgical intervention usually is necessary to save the animal’s life. Simultaneously fluid, electrolyte, and acid-base abnormalities need correction. For early cases of hypokalemic, hypochloremic alkalosis and dehydration, intravenous fluids consisting of 20 to 80 L of 0.9% sodium chloride with 25 to 100 mEq/L potassium chloride added are administered. Intravenous potassium should not be given at a rate greater than 1 mEq/kg/hr to prevent cardiotoxicity. For advanced cases with metabolic acidosis, balanced electrolyte solutions such as Ringer’s solution are indicated. Broad-spectrum antibiotics are appropriate if the integrity of the abomasal mucosa is questionable. NSAIDs are indicated to control pain, inflammation, and shock. Both standing right-sided and recumbent right paramedian approaches have been successful for correcting abomasal volvulus.^682,705

Prognosis

Establishing an accurate prognosis before surgery is optimal because at that time salvage remains a possibility and little expense has occurred. A second critical time is after surgery in cows not recovering appropriately. The decision will be whether to continue to treat (cost) or salvage, if that still is an option.

Preoperative assessment is difficult. In our experience, assessment cannot be based on a single clinical observation or serum biochemistry value. The best published studies looked at two different classifications of outcome: death versus survival and productivity versus nonproductivity. A logistic regression model,⁷⁰⁶ looking at heart rate, base excess, and serum chloride level, was developed as a preoperative predictor of death or survival. The study by Constable and colleagues found that four presurgical variables (hydration, heart rate, duration of inappetence, and AlP level) could be used to best predict cattle as productive or nonproductive after surgery.⁷⁰⁷

Surgical assessment of outcome has been investigated. The overall success rate of surgery varies between 61.5% and 86.3%.^708-711 The number of forestomachs involved in the twist has been found to adversely affect survival and productivity. Wallace found only 20% success in cattle with reticulo-omasal-abomasal volvulus.⁷¹¹ Another study reported success in 55% of cattle with omasal-abomasal volvulus and 87% success in cattle with only an abomasal volvulus.⁷⁰⁷ Edema of the abomasum carries a guarded to poor prognosis.^711-713 Edema around the proximal duodenum was associated with a poor outcome in Pearson’s study,⁷¹² but Fubini and co-workers found no association with outcome.⁷¹⁴ Purple discoloration of the abomasal serosa tends to bode poorly for long-term outcome, as does total distention of this organ, abomasal necrosis, and thrombosis of the gastric veins.^706,711 When it has been necessary to drain the abomasum of fluid to correct the twist, the animals have usually not done well.⁷⁰⁹ The measurement of intraluminal pressures of greater than 16 cm Hg also carries a poor prognosis because of mucosal damage.⁷⁰⁷ A logistic regression model using some of the surgical findings did not predict outcome any better than with the preoperative model.⁷⁰⁶

After correction, cattle with abomasal volvulus often have diarrhea for 24 hours. Feces then firm up to normal consistency. Postoperative clinical signs associated with a poor prognosis include melena, anorexia, persistent tachycardia, and dehydration.^709,713,715 In our experience, even if appetite and general attitude are initially good (24 to 48 hours after surgery), persistence of a loose low-volume stool 72 hours after surgery may indicate complications and possible vagal indigestion.⁷¹⁷ Once vagal signs develop, the survival rate is only 11.5% to 20%.^711,716 Prolonged treatment seems irrelevant, because neither surgical treatment (pyloroplasty, abomasal or ruminal fistula) nor medical treatment (prokinetic drugs or laxatives) has been shown to be effective.^672,709

Necropsy Findings

Cattle that die of abomasal volvulus are grossly dehydrated, and the abomasum is greatly distended or ruptured. The omasum often is also greatly distended when torsion occurs at the reticuloomasal junction. Cattle that die or are euthanized after developing postoperative complications have one or more of the following postmortem lesions: gastric compartment dilation, peritonitis, abomasal wall necrosis or ulcer, vascular thrombosis, or vagal nerve lesions.⁷¹⁷

Prevention and Control

Because factors predisposing to atony of the forestomach and abomasum probably are important in the genesis of abomasal volvulus, prevention should be similar to that outlined for LDA.

Definition and Etiology

Abomasal ulcers occur in cattle of all ages and rarely in sheep and goats. Signs of loss of gastric epithelium may range from no clinical signs, to hemorrhage and anemia and subsequent melena, to peritonitis if the erosive processes penetrate all layers of the abomasum. The exact cause of abomasal ulcers is still obscure and may be multifactorial. In calves, development of abomasal ulcers has been proposed to be associated with mineral deficiencies (mainly copper),^718,719 stress,⁷²⁰ proliferation of microorganisms (C. perfringens type A, fungi, or others),^720-724 and/or abrasion of the abomasal mucosa by roughage, geosediments, or trichobezoars.^725,726 However, all of these hypotheses have failed to demonstrate alone their involvement in the development of abomasal ulcers.^720,723,727 In adults the disease is associated with stress such as recent parturition, peak milk production, or presence of concurrent diseases (mainly those of the peripartum period), and with diets high in starch.^728-730 Lymphosarcoma of the abomasum also may lead to clinical signs of ulcer disease. Abomasal ulcers are also an adverse effect of NSAIDS.

Clinical Signs and Differential Diagnosis

Smith, Munson, and Erb⁷²⁹ have classified abomasal ulcers into four types: (1) nonperforating with minimal signs, (2) nonperforating with severe blood loss, (3) perforating with local peritonitis, and (4) perforating with diffuse peritonitis (Table 32-19). These classifications are useful for describing the various clinical pictures that may be observed when examining an animal with abomasal ulceration.

Table 32-19 Abomasal Ulcers

The mildest form (type I) is caused by nonperforating ulcers that do not result in extensive hemorrhage. Affected animals may have mild or no clinical signs. The signs are mild abdominal pain, shown by partial anorexia, decreased ruminal motility, and mild ruminal tympany. There is usually no febrile response. Manure may be normal or reduced in amount and stale because of prolonged transit. In some cases abdominal pain may be evident on manual pressure on the right ventral abdomen. TRP or indigestion may be suspected. In one study about two thirds of such cows had a positive test finding for fecal occult blood.⁷³¹

In cattle with ulcers that erode into major gastric blood vessels (type II), blood loss can be sufficient to cause signs of anemia and hemorrhagic shock. These animals have dark blood clots in their manure or tarry, black feces with the characteristic smell of partly digested blood. The mucous membranes may be pale, tachycardia may be pronounced, and the respiratory rate may be elevated. Total anorexia and ruminal stasis usually are present. The rumen may have a fluid consistency, and if the animal is able to stand, abdominal pain sometimes is evident. There are other possible sources of proximal gastrointestinal hemorrhage in cattle, but abomasal ulcers are by far the most common cause. Among them, bleeding abomasal ulcers must be differentiated from melena sometimes seen with intussusception or HBS (jejunal hemorrhage syndrome [JHS]). The PCV usually is increased with intussusception,^732,733 normal or increased in HBS,^734,735 and decreased with a bleeding ulcer.^736,737

Abomasal ulcers that perforate the serosal surface lead to localized peritonitis (type III) from contamination with abomasal contents. If the lesion is small or the local inflammatory reaction sufficiently swift, localized peritonitis results. This condition is most like TRP in presenting signs. The animal may be moderately febrile and partly or totally anorectic, and milk production may decrease acutely. There is evidence of abdominal pain, usually localized to the right ventral quadrant (positive withers pinch test). Ruminal motility may be absent, and mild bloat may be present. As with hardware disease, the signs usually abate over the course of a few days if the infection is successfully contained. In some cases the infection is confined to the omental bursa, where extensive fluid and pus may accumulate. The course of omental bursitis is much more prolonged than that of simple localized peritonitis and usually results in a guarded prognosis.

Major leakage from a perforating ulcer leads to acute diffuse peritonitis (type IV). The course of the disease usually is rapid, with signs of septic shock developing within 24 hours of the onset. Total anorexia and ruminal stasis are accompanied by tachycardia with a weak, thready pulse and a heart rate over 100 beats/min. Pain may be evidenced by grinding of the teeth or groaning. The extremities are cool, and the animal generally becomes recumbent. Abdominal enlargement may be evident as a result of both ruminal tympany and the accumulation of peritoneal fluid. Dehydration is detectable by skin pinch or by observation of the position of the eye in the orbit. Septic shock from other causes may be difficult to distinguish from that caused by perforated abomasal ulcers in the terminal stages of the disease. Diffuse peritonitis from uterine, cecal, or intestinal ruptures have the same final course. Abomasal volvulus of more than a day’s duration has similar characteristics but can be differentiated by the right-sided ping and fluid in the abomasum.

Clinical Pathology

The most useful diagnostic test for abomasal ulcer disease without visible melena is the fecal occult blood test. In an evaluation of 296 hospitalized cattle with gastrointestinal disease, this test had a sensitivity of 0.77 and a specificity of 0.97 for ulcers confirmed at surgery or necropsy.⁷³¹ The test is inexpensive and can be performed during the physical examination.

Abdominocentesis confirms diffuse peritonitis (a large quantity of abdominal fluid is obtainable); centesis fluid may contain leukocytes with phagocytosed or free bacteria, and even feed particles. In localized peritonitis the results of abdominocentesis may be normal.

Abdominal ultrasonography is also useful for the diagnosis and the evaluation of peritonitis (see section on abdominal ultrasound). Braun and colleagues reported that percutaneous ultrasound-guided abomasocentesis can be safely performed for the evaluation of abomasal fluid.⁷³⁸ The presence of blood or hemoglobin is principally associated with abomasal ulcers.^738,739

If peritonitis is present, leukocytosis usually is present, with neutrophilia predominating in many cases. The plasma fibrinogen is increased (over 700 mg/dL) in most cattle with peritonitis. This may be evaluated in the field with a glutaraldehyde coagulation test on whole blood. The hematocrit is normal or elevated with peritonitis, but plasma protein levels may be decreased as a result of protein accumulation in the peritoneal cavity or increased if dehydration is severe. If blood loss is severe, the PCV is decreased. Cattle over 5 years of age with a bleeding abomasal ulcer should be tested for bovine leukosis virus. Results of a complete biochemistry profile or blood gas analysis are nonspecific. In most cases, they reflect a digestive stasis (hypochloremic metabolic alkalosis), but in animals in shock a metabolic acidosis may be observed. BUN may be increased. This can be a result of blood degradation in the intestine or hypovolemia and prerenal azotemia. The utility of BUN in the diagnosis of abomasal ulcers by identifying digestive hemorrhage remains to be determined.

Pathophysiology

The specific events leading to erosion and ulceration of the abomasal mucosal epithelium are unknown but probably are similar to those in other species. Cytoprotective mechanisms include a mucous barrier, cloudy mucus containing bicarbonate ions to neutralize back-diffusing hydrogen ions, and high submucosal rates of blood flow to remove back-diffusing hydrogen ions. When these mechanisms are disturbed, gastric (abomasal) ulcers can occur. Stress, concurrent diseases, corticosteroids, and NSAIDs are among factors known to contribute.

Epidemiology

Abomasal ulceration occurs in cattle of all ages. At slaughter many calves are found to have clinically inapparent abomasal erosions and ulcers, with prevalence reported ranging from 32% to 76%.^740-743 In clinically affected calves, perforation with peritonitis (rather than hemorrhage) usually develops. In clinically normal slaughter cows, 20.5% had type I ulcers.⁷⁴⁴ However, a much lower prevalence (1% to 2.6%) of abomasal ulcers in healthy adult cows has also been reported.^745,746 In adult cattle with abomasal ulcers causing illness, approximately one third of clinical cases in a referral population had significant hemorrhage.⁷³⁶ Of these, half had lymphosarcoma and for the most part were older than 6 years of age. The age of the cattle with non—tumor-associated bleeding ulcers was generally younger (7 of 12 were less than 5 years old). In the remaining two thirds of the cattle, ulcers had perforated, with about half having diffused and half having localized peritonitis.⁷⁴⁷ Most adult cattle with abomasal ulcer disease are in the first month after calving and have a concurrent disease. Many cows have been discovered to have an abomasal ulcer at surgery for displaced abomasum. Metritis, mastitis, and ketosis are the other diseases commonly seen with abomasal ulcers. The incidence of abomasal ulcers apparently increased with the advent of heavy corn silage and high-moisture corn feeding. In the recent past, as feeding and management practices have addressed the most common abomasal displacements, the incidence of ulcer disease has also decreased.

Necropsy

Cattle with bleeding abomasal ulcers resulting in death are very pale and may have blood or bloody fluid throughout the distal gastrointestinal tract. The lesion in the abomasum is typically small and involves an abomasal blood vessel in the submucosa. Most bleeding and perforating ulcers were found in the fundic portion of the abomasum in the region of the proper gastric glands. The most ventral portion of the abomasum in its normal position is frequently affected.^{737,745,746,748} Most animals have a single ulcer significantly bleeding, but approximately 60% have one or more additional ulcers or erosions.^737,745 Cattle with diffuse peritonitis have many liters of foul-smelling fluid in the peritoneal cavity. Fibrin usually covers the serosal surface of all abdominal organs. The defect in the serosal surface of the abomasum is usually nearly round and 3 to 6 cm in diameter. Abomasal fluid freely enters the peritoneal cavity. Omasal bursitis may be present, with the omental recess filled with purulent to fibrinous fluid. In these cases the remainder of the abdomen may not be grossly affected. Asymptomatic abomasal ulcers (often 50 to 200) may be found coincidentally in cattle that die of septic metritis or mastitis. These ulcers generally show no signs of hemorrhage and go undetected until necropsy.

Treatment and Prognosis

Treatment is aimed at correcting dietary problems, reducing stress, ameliorating concurrent disease problems, and initiating specific therapy for the clinical problems caused by the ulcer. Removal of high-energy feedstuffs and replacement with good-quality hay plus confinement to a stall are beneficial.⁷²⁸ The buffer effect of food is very important for the control of abomasal pH. Consequently, the return to a normal appetite is the main goal of the treatment of abomasal ulcers.⁷⁴⁹

Blood transfusions may be necessary for cattle that have lost enough blood to lower the hematocrit to 14% or below. Usually 4 to 6 L given once is adequate, but repeated transfusions occasionally may be necessary. Cross-matching usually is not necessary for cattle unless repeat transfusions are performed over a period of more than 3 days. Broad-spectrum antibiotics are administered to cattle with signs of peritonitis. Principles and details on the treatment of peritonitis are described in the section on peritonitis in ruminants. Intravenous or oral fluids may be necessary to treat dehydration and metabolic or acid-base disturbances that occur concurrently. Animals with diffuse peritonitis must be given intravenous fluids with caution because of the risk of pulmonary edema associated with the low colloid oncotic pressure of their plasma.

Numerous recent studies have been performed to evaluate the effect of different therapeutic agents on abomasal pH of healthy calves. Results of these studies have been summarized by Constable and colleagues.⁷⁴⁹ The therapeutic agents studied in normal calves included oral administration of an antacid agent containing aluminum hydroxide and magnesium hydroxide (25 mL and 50 mL, tid), oral administration of specific H₂-antagonists (cimetidine, 100 mg/kg and 50 mg/kg, tid; and ranitidine, 10 mg/kg and 50 mg/kg, tid), and oral administration of the proton pump inhibitor omeprazole (4 mg/kg sid). All these treatment regimens induce an increase in mean 24-hour abomasal luminal pH. Oral administrations of the antacid agent induced a dose-dependant increase in luminal pH and were more efficacious when administered postprandially. Because some deleterious effects were observed when this antacid was administered at the dose of 50 mL tid, this should be considered the maximal dosage rate in calves.⁷⁴⁹ Cimetidine (100 mg/kg tid) was the most effective. However, ranitidine (50 mg/kg tid) was the most cost-effective in theses studies. Results of theses studies need now to be confirmed in ill calves. In adults, oral administration of these therapeutic agents is of doubtful benefit because of dilution in the rumen and slow release into the abomasum. Oral medications administered after stimuli that induce reflex esophageal groove closure would be more likely to have the desired effect. Traditional stimuli to close the esophageal groove have included copper sulfate solutions and 10% sodium bicarbonate solution. Vasopressin (0.25 IU/kg IV) was shown to induce reliable abomasal deposition of materials given by drench to adult goats.⁷⁵⁰ Intravenous administration of H₂-antagonists at lower doses may be efficacious, but their use by this route is cost-prohibitive ($100 to $200 USD per day) or reserved for very high-value animals. In our clinic in Quebec, we use ranitidine 1 to 1.5 mg/kg IV tid for high-value animals; our clinical impression is that this is effective.

The prognosis is good for ulcers that are not bleeding and not perforated. For those animals that stop bleeding and those with localized peritonitis, survival and eventual return to normal function can be expected. Many dairy cattle stop lactating during the acute course of the illness and do not return to milk until the next lactation. Because abomasal ulcers generally occur within the first month after calving, most of these animals are salvaged for slaughter. Most cattle with diffuse peritonitis die despite aggressive specific therapy. Early recognition and immediate surgery followed by antibiotic and fluid therapy may save some valuable individuals. Cattle with ulcers that occur secondary to lymphosarcoma should be euthanized or slaughtered.

Prevention and Control

Because the exact cause of development of abomasal ulcers is unknown, prevention is difficult. Dietary management that reduces other abomasal diseases likewise reduces the incidence of abomasal ulcers. Avoiding abrupt changes in rations and including adequate fiber sources of sufficient particle size to facilitate normal ruminal function also promote normal abomasal function. Minimizing stress caused by overcrowding, excessive competition, and adverse environmental conditions, and minimizing mastitis and metritis should also reduce problems with abomasal ulcers. Elimination of animals infected with the bovine leukosis virus from the herd eliminates lymphosarcoma as a cause of abomasal ulcers. Judicious use of corticosteroids and NSAIDs is also important.

Definition and Etiology

A syndrome of abomasal dilation and mechanical transport failure has been described in adult Suffolk sheep.^751-754 The condition resembles but is uniquely different from abomasal impaction of cattle wintering on very-poor-quality roughage. It has been mainly reported in Suffolk sheep but a similar syndrome has been described in two Hampshire,⁷⁵⁵ one Dorset⁷⁵⁶ and one Texel sheep.⁷⁵⁷ No hereditary pattern of disease has yet been found.^753,754

Clinical Signs and Differential Diagnosis

The disease is primarily manifested by anorexia and weight loss. Most patients eventually die. Animals described in reports from several teaching hospitals were adults of both sexes.^751-754 Not all animals had all of these signs, but the following have been reported: watery green diarrhea or normal feces; ruminal tympany; pear-shaped abdominal distention; increased, normal, decreased, or absent ruminal contractions; a palpable firm mass in the right lower abdomen; mild abdominal pain; tachycardia; duration of observed signs from days to months; partial to total anorexia; dullness and depression; marked to undetectable weight loss; ketonuria.

Wasting diseases of sheep include malnutrition, parasitism, dental problems, Johne’s disease, caseous lymphadenitis, other chronic infections, and neoplasia. Abomasal emptying defect is distinguishable by the palpable abomasum in advanced cases and the exclusion of other possible problems. Other causes of abomasal enlargement or impaction resembling those reported in cattle must also be considered. However, when a mature Suffolk from a well-nourished flock shows weight loss and a palpable abomasum, this syndrome must be considered highly likely. Confirmation should involve response to therapy but may require necropsy or exploratory surgery.

Clinical Pathology

Reports on cases seen in North America have found hematologic and blood chemical determinations of little benefit in the diagnosis. The hypochloremic metabolic alkalosis common in cattle with abomasal problems has not been consistently observed in affected sheep. Elevated ruminal chloride ion values have been the most consistent laboratory findings in published reports.^752,753,758 The normal ruminal chloride level in sheep is 8 to 15 mEq/L; affected sheep have had values ranging from 34 to 130 mEq/L. Mild hypocalcemia was observed in all cases in one report.⁷⁵³

Pathophysiology

The mechanisms underlying the dilation of the abomasum and the failure to transport ingesta to the intestines are unknown. None of the problems commonly associated with abomasal impaction and dilation in cattle have been identified in affected Suffolk sheep. Recently Pruden and colleagues advanced that abomasal emptying defect of Suffolk sheep may be an acquired form of dysautonomia.⁷⁵⁴

Epidemiology

The disease has been mainly reported in sheep of the Suffolk breed. The disease has mostly been seen in winter months in association with lambing and feeding of concentrates. Both rams and ewes have been affected. Most cases are sporadic but at least two outbreaks have been reported.^753,754 The incidence in one report was 13 of 92 mature ewes affected in the flock during one winter.⁷⁵³ In the other, five ewes of the same flock (200 ewes) were submitted for necropsy the same day.⁷⁵⁴ In both studies, pedigree analysis of affected sheep in the flock showed no hereditary pattern. One report from a diagnostic laboratory in England described abomasal impaction in a Texel ewe and in a Suffolk ram that were simultaneously diagnosed as having scrapie.⁷⁵⁷ It remains to be seen if any causative connection exists between the two diseases. Because no antemortem tests exist for the diagnosis of scrapie, this relationship will be difficult to establish. In one study, six sheep were immunohistochemically tested for scrapie; five were negative, and one was positive and presented equivocal microscopic lesions.⁷⁵⁴

Necropsy Findings

The abomasum is greatly distended in sheep that die of this condition. The contents are either dry or liquid but most often have resembled normal ventral ruminal sac contents. The pylorus has always been patent. Normal ingesta have been observed throughout the remainder of the intestinal tract. Incidental findings have included aspiration of ruminal contents and subsequent pneumonia, abomasal ulcer with local peritonitis, passive congestion of the liver, megaesophagus, and esophageal ulcers. Reports of histopathologic findings include no lesions other than thinning of the abomasal muscle layers⁷⁵³ (presumably as a result of stretching), mononuclear cell infiltration of the main muscle layers of the abomasums,⁷⁵¹ and one case of myxomatous changes in the abomasal branches of the vagus nerve.⁷⁵² Chromatolytic and necrotic neurons without signs of inflammation within the celiacomesenteric ganglia were found in six of six sheep examined.⁷⁵⁴

Treatment and Prognosis

Medical therapy alone with cathartics and laxatives has been of limited benefit. Mineral oil, dioctyl sodium sulfosuccinate, and magnesium sulfate have all been used. Neostigmine and calcium gluconate were not useful.⁷⁵¹ Abomasotomy has led to death from complications in many affected sheep, but those that have survived more than 2 days and have been treated with metoclopramide (dosage not reported) have shown varying degrees of recovery. Metoclopramide is a dopamine antagonist that has been used in ruminants to facilitate abomasal emptying. However, experimental studies in cattle and sheep have failed to demonstrate any beneficial effect of metoclopramide on abomasal emptying.^759,760 On the other hand, erythromycin, a motilin agonist, has been shown to increase abomasal emptying rate in cattle.^759,760 Its utility in sheep remains to be determined. Despite these successes, most affected sheep die of cachexia. Because of the expense, poor response, and risks associated with abomasotomy, this treatment is reserved for valuable breeding stock.

Prevention and Control

Until more is known about the pathogenesis of this specific defect in abomasal function in Suffolk sheep, no useful recommendations for prevention can be made.

Definition and Etiology

Abomasal impaction is the accumulation of firm ingesta in the abomasum with failure of aboral transport. Depending on the cause, abomasal impaction can be classified as primary or secondary. In primary abomasal impaction, no underlying cause can be identified and the impaction is considered idiopathic. On the other hand, secondary abomasal impaction can be the result of feeding poor-quality, coarse roughage as the sole feed. Several animals in a herd may be affected over a short period. Calves may also have impaction of the abomasum caused by eating bedding or indigestible objects when fed low-quality milk replacers. The distended abomasum is filled with a firm mass of fibrous ingesta. Animals on low-fiber diets may consume wood or baling twine. Hairballs occasionally accumulate in the abomasum of calves. Indigestible material creates a mechanical outflow obstruction. Abomasal distention may occur with normal diets after correction of abomasal volvulus, secondary to reticuloperitonitis, or secondary to the development of adhesions between the abomasum and the rumen and or the abdomen. These conditions are referred to as vagal indigestion. Lymphoma involving the abomasum or other space-occupying lesions adjacent to the pylorus may lead to abomasal distention. Abomasal emptying defects of Suffolk sheep were addressed in the previous section.

Clinical Signs and Differential Diagnosis

Beef cows with abomasal impaction develop abomasal and ruminal enlargement over a period of days to weeks. Closely monitored animals have reduced feed intake and a reduced volume of firmer than normal feces. The animal may have bilateral ventral abdominal enlargement and bulging of the left paralumbar region. Ruminal contractions are of normal or increased frequency but often reduced in amplitude. In the later stages of the disease, ruminal motility often is absent. Cattle with advanced abomasal impaction may be recumbent and groan with each respiration. The consistency of the ruminal ingesta, as judged by ballottement, may be more fluid than expected on the basis of the coarse diet in some animals, whereas other animals have a uniformly firm and distended rumen. The pulse and respiration are usually normal until the animal is near death, at which time tachycardia develops. The abomasum may be palpable as a firm mass following the right coastal arch. Rectal examination reveals a distended rumen; often the ventral sac extends to the right body wall (L-shape rumen). The pyloric part of the distended abomasum may be palpable in the right ventral quadrant. Wintering beef cows usually are pregnant, and therefore the uterus prevents palpation of the abomasum. Mucus may be all that clings to the clinician’s sleeve after rectal examination. Clinical signs in adult dairy cows are reported to be inconsistent, with the exception of decreased appetite.⁷⁶¹ In calves the abomasum may fill most of the abdomen and be doughy or firm on external palpation. The body condition of affected animals is invariably poor because negative energy balance precedes and is amplified by the impaction. If the abomasum ruptures, signs of generalized peritonitis occur. Death usually follows within hours of rupture.

In dairy cows, abomasal impaction should be considered in the differential diagnosis of nonspecific clinical signs of decreased milk production and appetite.⁷⁶¹ Conditions that cause dehydration and bilateral abdominal distention with absence of feces must be considered in the diagnosis. In many of these cases exploratory celiotomy is necessary to arrive at a definitive diagnosis.

Clinical Pathology

The hypochloremic, metabolic alkalosis typical of upper gastrointestinal obstruction in ruminants does not always develop in abomasal impaction.⁷⁶¹ Initially some fluid ingesta may pass through the abomasum, preventing chloride sequestration. However, some cattle have metabolic alkalosis with chloride accumulating in the rumen (internal vomiting). Terminally a metabolic acidosis from starvation may mask the metabolic alkalosis. Anemia and leukopenia can accompany the cachexia of chronic abomasal impaction in poorly fed animals. If abomasal rupture has occurred, profound hemoconcentration and leukopenia are present. Abdominocentesis generally is not useful in diagnosing abomasal impaction, because peritoneal fluid is abnormal only after abomasal rupture.

Pathophysiology

Animals fed roughage that is poorly digestible and incapable of meeting their energy requirements consume as much as the rumen will physically permit. The flow of ingesta from the forestomachs to the abomasum normally contains only small, finely digested particles of forage material. With chronic engorgement of highly lignified, poorly digestible forage, larger particles escape the forestomach and accumulate in the abomasum. Once a mass of fiber forms in the abomasum, further accumulation of particulate material is enhanced. With time, the mass fills the abomasum. Additional ingesta distend the abomasum to several times normal size. Also, abomasal secretion may be inhibited by the cachexia and chronic distention of the organ.

Abomasal transport failure after correction of abomasal volvulus is typical of vagal indigestion syndrome. Abomasal wall and vagal nerve damage, as well as peritonitis occurring secondary to the volvulus, prevent the return of normal abomasal muscular activity.⁷⁶² Vagal tone sometimes increases, and bradycardia is observed. Hypochloremic, metabolic alkalosis does develop frequently, with chloride accumulating in the ruminoreticular contents. The abomasum distends moderately, presumably as a result of atony.

Pyloric obstruction caused by foreign bodies or occlusion caused by lymphoma leads to mechanical outflow obstruction and must be considered. Chloride escapes back into the rumen, and metabolic alkalosis develops. The abomasum retains motility, but it is ineffective in moving ingesta into the duodenum.

Necropsy Findings

Emaciation and a firm, grossly enlarged abomasum are consistent with primary abomasal impaction. In Holstein cows a syndrome has also been described in which the impaction affected only the pyloric part of the abomasum.⁷⁶¹ The abomasal contents resemble normal, dry ruminal contents. The rumen is also enlarged but either filled with homogenous, watery ingesta that lack normal stratification or impacted with dry ingesta, similar to the abomasum. The abomasum is dilated, flaccid, and filled with fluidy ingesta if secondary to an abomasal volvulus. Intraluminal foreign body or tumor involvement of the abomasal wall is self-evident.

Prognosis

Because most cases of abomasal impaction are quite advanced when brought to the attention of the veterinarian, treatment usually is unrewarding. In dairy cows the short-term prognosis was reported to be good (93%) for impaction that affects only the pyloric antrum and guarded (50%) for impaction involving the entire abomasum.⁷⁶¹ The clinician must weigh the severity of the metabolic disturbances and the likelihood of recovery. Salvage by slaughter is often the most economic recommendation. If therapeutic measures do not resolve the impaction, death usually occurs within a few days of the onset of severe signs.

Treatments

Medical management includes correction of fluid and electrolyte abnormalities. Early cases may be resolved with easily digestible feeds, aggressive fluid therapy, and oral administration of laxatives such as mineral oil (4 L daily). Metoclopramide at a dose of 0.3 mg/kg given SC four to six times daily has been used to increase passage of ingesta through the pylorus. However, recent studies have failed to demonstrate any efficacy of metoclopramide on increasing abomasal motility.^763,764 Erythromycin (8.8 to 10 mg/kg IM bid) and bethanechol (0.07 mg/kg SC tid) alone or in combination with metoclopramide (0.1 mg/kg SC or IM tid) have been reported to increase abomasal emptying rate.^763,764 Pregnancy may be terminated by induction of parturition with corticosteroids and/or prostaglandin, leading to improved comfort.

Different approaches have been proposed for a surgical treatment of abomasal impaction. Baker⁷⁶⁵ recommended rumenotomy followed by installation of a nasogastric tube inserted into the abomasum through the omasum. Through the indwelling tube laxatives and emulsifiers may be given during the postoperative days to aid in softening and removing the abomasal contents. Mineral oil (8 mL/kg/day), dioctyl sodium sulfosuccinate (50 mg/kg/day), magnesium hydroxide (1 g/kg/day), or magnesium sulfate (2.5 g/kg/day) have all been recommended. Right flank or right paracostal approaches could also be used in order to gain direct access to the abomasum. Abomasotomy could be performed to remove the abomasal content, but it has not been reported successful in restoring abomasal function.⁷⁶⁶ External massage may help break up the contents of the abomasum. Intraluminal administration of 5% dioctyl sulfosuccinate solution or saline could also be performed.⁷⁶¹

Prevention and Control

Prevention of primary abomasal impaction requires proper dietary management of cattle in cold weather. Because animals outside without shelter have substantially increased maintenance energy requirements in cold, windy weather, straw or corn stover (stalks) is not adequate as the sole feed. Concentrates and better-quality forage prevent abomasal impaction. Monitoring body condition during winter weather alerts the good manager that supplemental feed is needed before abomasal impaction occurs.

Definition and Etiology

Several conditions may lead to obstruction of the flow of ingesta through the intestinal tract. They can be divided into functional and mechanical obstructions. Functional obstructions (pseudoobstruction or ileus) are the consequence of neuromuscular perturbations of the gastrointestinal tract. Mechanical obstructions are the consequence of physical obstruction of the gastrointestinal tract secondary to digestive tract lesions (intussusception, volvulus, or congenital lesions) or extradigestive lesions (mesenteric fat necrosis, fibrous adhesions, or hernia). Each of the specific diseases is discussed in the following paragraphs and summarized in Table 32-20.

Table 32-20 Causes of Intestinal Obstruction in Ruminants

LI, Large intestine; SI, small intestine.

Clinical Signs and Differential Diagnosis

Acute manifestations of obstructive diseases include a reduced amount of feces or failure to pass feces, progressive abdominal enlargement with areas of tympanic resonance on the right side of the abdomen, and sometimes colic. If pain is severe, forestomach atony may occur. Mechanical obstructions may lead to circulatory shock and collapse. Electrolyte abnormalities depend on the site of the obstruction; those near the duodenum or pylorus lead to sequestration of abomasal secretions and result in hypochloremic, hypokalemic metabolic alkalosis. Obstructions of the cecum, colon, or rectum may lead to dehydration without alkalosis. If bowel necrosis or rupture occurs, acidosis may result from the circulatory collapse that accompanies peritonitis and the absorption of toxins.

Definition and Etiology

C. perfringens is a toxin-producing, anaerobic, spore-forming rod. It is a variable species that causes a variety of diseases in human beings and animals. Some biotypes are normal inhabitants of soil, and some are commensal intestinal organisms of animals. A sometimes confusing nomenclature has evolved to organize the complexity of C. perfringens biology. Clinical isolates are assigned to one of the types (A through E) on the basis of possession of the major toxins (alpha, beta, epsilon, iota) (Table 32-21). In addition to these four major toxins, strains of C. perfringens may produce any of at least eight other recognized soluble antigens, some of which have pathogenic importance and could be called toxins. Beta 2–toxin may be an important toxin as well.⁸²⁵ Most of these antigens are named with Greek letters.⁸²⁶ The soluble C. perfringens toxin responsible for one type of food poisoning in humans has not received a Greek-letter name but is commonly known as enterotoxin (or CPE for C. perfringens enterotoxin). Enterotoxin is also the general name for toxins that affect the intestines, and many of the C. perfringens antigens with Greek-letter names are also enterotoxins. In this discussion the toxin that causes food poisoning in human beings is denoted CPE to distinguish it from enterotoxin as a class of toxins. CPE is not recognized as the major component of classic C. perfringens disease in animals, but it may be important in some cases.^827,828

Table 32-21 Types of Clostridium perfringens by Toxin Type and Diseases That Have Been Attributed to the Type*

The different biotypes of C. perfringens cause different diseases because they have different toxins, but a clear-cut assignment to one of the groups is not always possible, and overlap is considerable in the clinical signs caused by the various toxins. Many different diseases in many different animals have been ascribed to C. perfringens, but the ubiquitous nature of the organism and the fact that it rapidly overgrows into tissues after death makes the significance of its isolation questionable at times.

One additional potentially confusing bit of nomenclature concerns the term “enterotoxemia.” Although this term is widely applied to various diseases caused by C. perfringens, it is strictly appropriate only for diseases in which the major signs are caused by systemic spread of the toxin in the blood.

One group of diseases caused by C. perfringens type C is commonly called “hemorrhagic enterotoxemia,” even though the disease is not always hemorrhagic and, although the toxin may incidentally reach the circulation, it is produced in the intestine and exerts its major effects locally. A better descriptive name for this disease has been proposed to be necrotic enteritis.⁸²⁹ It is important to realize that many of the effects of other biotypes of C. perfringens are systemic and that enteric clinical signs may be entirely lacking with disease caused by C. perfringens types A and D. Each type is discussed in the following paragraphs. Type E is only occasionally isolated from livestock and is not discussed.

Diagnosis of Disease Caused by Clostridium Perfringens

Meaningful diagnosis of C. perfringens as the cause of death or disease in an animal requires an integrative, open-minded approach. Type A is routinely isolated from soil and clinically normal animals. Types C and D are only rarely isolated from soil but can be isolated from asymptomatic individuals, especially those with neutralizing antibody to toxin. The bacterium proliferates after death, often crowding out other enteric organisms and invading tissues beyond the gut. The isolation of C. perfringens from a necropsied animal is not by itself sufficient basis for the diagnosis; however, if toxin is also demonstrated in gut contents and the history and lesions are compatible, a diagnosis of death from C. perfringens intoxication can be made.

Until recently, an isolate of C. perfringens was assigned to one of the five biotypes by demonstrating toxin production with mouse-protection assays or ELISA techniques. This has been replaced by a multiplex PCR technique that detects the genes for toxin production in a clinical isolate.⁸³⁰ CPE, which causes food poisoning in human beings, can be detected with commercially available assays and is also detected by the multiplex PCR technique.⁸³¹ Meaningful samples for bacterial isolation come from freshly dead animals. Samples of gut contents should be collected into sterile containers and cooled or frozen. In addition to typing bacterial isolates, demonstration of toxin itself in gut contents may aid in diagnosis. False-negative results may occur in type C disease if proteases inactivate the beta-toxin.

In the absence of definitive microbiologic evidence, a presumptive diagnosis of type C or D disease must be based on the history, clinical signs, pathologic findings, and differential diagnoses. Administration of toxoid vaccines is cheap and effective and may be recommended without conclusive evidence for causation. This “whole herd” protection test may be as close as one gets to definitive diagnosis in field situations. Examination of gut-content smears from various levels of the gastrointestinal tract to demonstrate large numbers of bacteria resembling C. perfringens may be a helpful piece of information, but the significance of such a finding by itself is questionable. Glucosuria in urine obtained from the bladder at necropsy is often seen in sheep (but not other species) with type D disease.

Type D disease should be distinguished from other causes of acute death (see Chapter 14). A history of sudden death in a rapidly growing, apparently healthy individual is characteristic. A single lamb is much more likely to have overeating disease than is a twin. Other causes of acute disease in well-fed individuals include systemic pasteurellosis (lambs), acute bloat, grain overload, polioencephalomalacia, and thromboembolic meningoencephalitis (cattle). These generally have a longer disease course than type D enterotoxemia.

Definition and Etiology

C. perfringens type C elaborates the alpha (hemolytic)-toxin common to all types, in minor amounts, and the beta-toxin in major amounts. The amount of beta-toxin produced may determine the pathogenicity of a type C strain. In addition, type C strains produce the cytotoxic and hemolytic alpha-toxin, which is used to assign strains to group C if they have lost the ability to produce beta-toxin in culture.⁸³⁹ Beta-toxin appears capable of producing all the signs of necrotic enteritis; the role of alpha-toxin or CPE in disease is unclear.⁸²⁹

Necrotic enteritis is primarily a disease of neonates and occurs in calves, lambs, foals, and piglets. A similar disease in adult sheep, known as struck, has a very limited geographic range in Great Britain.

Clinical Signs and Differential Diagnosis

Affected animals may die acutely without diarrhea, but this is rare. The diarrhea may be yellow or, in more hemorrhagic cases, brownish. Gray-red streaks of necrotic mucosa may be present in the stools. Foals with type C disease at first show acute abdominal pain, then explosive yellow diarrhea that becomes brown and hemorrhagic.⁸³⁹ Animals become dehydrated, anemic, weak, and moribund, despite intensive therapy. Morbidity and mortality are high, but the disease is quite sporadic in occurrence. Salmonellosis and coccidiosis should be considered in the differential diagnosis, but necrotic enteritis is the more common disease in very young animals.

Pathophysiology

The causative beta-toxin is readily destroyed by proteolytic enzymes such as trypsin. The neonate is especially predisposed to beta-toxin attack by the presence of trypsin inhibitors in colostrum, the function of which is to prevent proteolytic degradation of immunoglobulins. Necrotic enteritis in humans is believed to be caused by decreased proteolytic activity arising from low-protein diets or the consumption of sweet potatoes, which contain heat-stable inhibitors of trypsin.⁸²⁹ The scattered cases of necrotic enteritis in adult animals may be the result of similar dietary factors. Type C disease has been reproduced experimentally in maturing lambs by administering type C cultures and soybean flour, which contains potent protease inhibitors.⁸⁴⁰

Ingestion of a protein-rich diet into a protease-deficient intestinal tract allows rapid growth of C. perfringens organisms. The bacteria attach to the villi, and elaboration of the cytotoxic beta-toxin results in necrosis and invasion of deeper intestinal layers. Death may result from the direct effects of the severe diarrhea or may be caused by secondary bacteremia or toxemia from the compromised gut barrier.

Epidemiology

Neonates that ingest type C organisms during the first few days of colostrum feeding are at risk. They pick up the organism from an environment contaminated by an asymptomatic shedder or from contaminated feed. Type C may be isolated from asymptomatic individuals on occasion, but it is not considered a normal commensal as is type A. Once established on a premises, the disease may become endemic. In foals the disease is significantly associated with housing in a stall or drylot during the first 3 days of life, previous presence of livestock on the farm, low amounts of grass hay fed postpartum, being born on dirt, and having stock horse parentage (e.g., quarter horse, Paint). Feeding smaller amounts of grain prepartum is associated with decreased incidence of the disease.⁸⁴¹

Necropsy Findings

Necrosis of the mucosa of the small intestine, especially the jejunum, is the consistent finding in all species. The large intestine may be normal except for intraluminal blood. The peritoneal cavity often contains excessive fluid, which clots when exposed to air. The mesenteric lymph nodes may be hemorrhagic. Microscopically, affected gut shows hemorrhage throughout the mucosa and submucosa. The tips of the necrotic villi are covered with numerous, large, gram-positive rods.

Treatment, Prevention, and Control

Once a case becomes clinically apparent, treatment generally is unsuccessful because of the fulminant nature of the disease. Foals can be treated with supportive intravenous broad-spectrum antibiotics (to cover gram-negative bacteremia caused by loss of gut integrity), fluids, plasma (intravenous and oral), withdrawal of milk for 24 hours, oral metronidazole, and intravenous C. perfringens types C and D antitoxin. Metronidazole (10 mg/kg PO or IV given twice daily) can be given to at-risk foals in the face of an outbreak, beginning at 8 to 12 hours of age and continuing for 5 days.⁸⁴² Toxoid has been administered to horses⁸⁴³ to control the disease on an apparently endemic property, with good results. Antitoxin* may be given to animals at risk in an outbreak, and C. perfringens types C and D are common components of multivalent vaccines. The primary vaccination series consists of two injections 1 month apart, with the final dose given 2 weeks before parturition, and a yearly booster thereafter. Neonates should be vaccinated at 8, 12, and 16 weeks of age on problem farms.

Definition and Etiology

Enterotoxemia caused by C. perfringens type D is a disease of major importance in sheep and of lesser importance in cattle and goats. It is caused by strains of the bacterium that produces the epsilon-toxin. This type is not a common soil organism, as is type A, but it may be isolated from the feces of apparently normal sheep and, less often, cattle.⁸⁴⁴ Most clinical disease occurs in animals fed a highly nutritious diet, especially grain-fed livestock.

Clinical Signs and Epidemiology

The sudden death of a well-fed, rapidly growing animal is the most common presentation of enterotoxemia. The disease may run its course in 30 to 90 minutes, with affected lambs showing ataxia, trembling, stiff limbs, opisthotonus, convulsions, coma, and death. At the onset of clinical signs, the animal is hyperglycemic. At death it is glucosuric. The differential diagnoses should include other causes of neurologic signs and acute death: anthrax, botulism, black disease, leptospirosis, listeriosis, enterotoxigenic E. coli infection, septicemia, polioencephalomalacia, toxic indigestion (grain overload), systemic pasteurellosis, and tetanus.

Sublethal doses may result in brain damage and focal symmetric encephalomalacia (see diseases of nervous system, Chapter 35). Affected lambs are dull and unresponsive to normal environmental stimulation. The major differential diagnosis is polioencephalomalacia. Experimental intravenous injection of type D epsilon toxin into calves produced neurologic signs and severe acute pulmonary interlobular edema. The histologic lesions in the brain consisted of perivascular proteinaceous edema in the interna capsule, thalamus, and cellebellar white matter, whereas in the lung intraalveolar and interstitial edema were found. These are similar to some of the lesions found in sheep and goats with type D enterotoxemia.⁸⁴⁵

The disease in goats is usually confined to the intestinal tract and seldom involves system signs seen in sheep.⁸⁴⁶

Pathophysiology

In some feedlot situations the animal ingests C. perfringens type D on a regular basis, but the acid environment of the abomasum and continuous peristalsis, as well as low amounts of fermentable substrate, conspire to keep bacterial numbers low and moving out of the animal. The intestinal environment also influences the amount of toxin produced.

Some factor of overnutrition, often heavy grain feeding or very rich pasture, provides substrate for rapid proliferation of the type D organism, leading to elaboration of the prototoxin. Cleavage of the prototoxin by proteases yields the active toxin. Epsilon toxin increases intestinal permeability, causing edema in a variety of organs, notably the lungs, kidney (hence the name “pulpy kidney disease”), and brain (focal symmetric encephalomalacia). Excess pericardial, peritoneal, and pleural fluid (with or without fibrin) and subcapsular petechiation in the kidneys may be seen.⁸⁴⁷ These lesions cause rapid deterioration and death. Hyperglycemia and glucosuria are the result of massive hepatic glycogen release caused by the epsilon-toxin.

Necropsy Findings

Postmortem lesions are inconsistent. The pulpy kidney lesion may not be seen in freshly examined specimens. The epicardium, serosa, thymus, and diaphragm may have small areas of hemorrhage. The pericardial sac often contains excess fluid. The lungs may be edematous. Glucosuria is considered a hallmark of type D enterotoxemia but is sometimes not present. Histologic lesions include pleural and interlobular and perivascular edema in the lung, as well as perivascular edema in the brain of some affected animals.⁸⁴⁷

Treatment, Prevention, and Control

If initiated at the first suspicion of overeating disease, type D antitoxin and oral antibiotics (sulfa) may have dramatic results.⁸⁴⁸ The diet should be adjusted downward in outbreaks to try to minimize the substrate, especially starch, that reaches the bacteria. Lambs on rich pasture should be moved to poorer pasture or corralled and fed hay until they have been vaccinated twice. Lambs and calves brought into a feedlot should have the concentrate ration increased slowly to minimize microfloral disruptions.

Antitoxin can be given in an outbreak, but previous vaccination is more effective. Vaccination with type D bacterin-toxoid is effective in preventing disease. Two doses are given 14 to 56 days apart, before heavy grain feeding or exposure to rich pasture begins. The aluminum hydroxide adjuvanted vaccines may cause raised subcutaneous lumps (most noticeable on goats) that may go on to abscess. Dairy goats fed continuous high-grain rations may need to be vaccinated more often for continuous protection. One study of three commercial vaccines found that one of the vaccines provoked no antibody response in goats 14 days after vaccination and that at 28 days after vaccination, even the goats that had responded to the other two vaccines had titers no higher than unvaccinated controls.⁸⁴⁹ The vaccine is not licensed in the United States for use in goats but is routinely used. Bummer lambs may be protected by feeding bovine colostrum from cows vaccinated several times with the sheep vaccine to provide high titers in colostrum.⁸⁵⁰ Colostral titers from the dam are protective to 12 weeks of age, after which vaccination should be used to provide active immunity against the disease.⁸⁵¹

Definition and Etiology

Toxic signs can appear in ruminants^854,855 and occasionally in horses⁸⁵⁶ that ingest large quantities of oak buds, oak leaves (green or dried), or acorns. Most species of oak (Quercus species) cause similar signs when ingested, although there are marked differences in the amount of toxins among the 75 oak species.⁸⁵⁷ The metabolites of oak tannins and volatile phenols present in the buds, leaves, twigs, and acorns are responsible for causing toxicosis. The mouth, esophagus, gastrointestinal tract, and kidneys (renal tubular nephrosis) are the organs most affected. Because they are less selective in what they ingest, cattle seem to be the most frequently affected species. Signs begin shortly after ingestion of 50% or more of the diet as oak, and young cattle (under 300 kg) often appear to be more severely affected than adult cattle.

Factors leading to toxicosis include the presence of large acorn crops when forage is scarce, wind or hail that causes large numbers of acorns to drop suddenly, or the sudden presentation of oak buds and young leaves to hungry cattle, as in spring windstorms or snowstorms that cover the grass and break branches. In the southwestern United States, range cattle regularly consume some oak species, which are apparently highly palatable and nutritious.⁸⁵⁸ The condition has been described wherever oak grows, including most of the United States, France, Great Britain, Germany, Sweden, Australia, China, and South Africa.

Acorn calf syndrome is completely different from the oak toxicosis described in this section. Acorn calves are congenitally malformed calves born to dams that ingest large numbers of acorns under poor forage conditions during the second trimester of pregnancy. The cause appears to be a combination of poor nutrition and exposure to acorns. The calves have very short leg bones and may have abnormal hoof development and a short or long narrow head. In badly affected herds as many as 15% of calves are affected. The disease has been reproduced experimentally. Supplementation of the herd with adequate protein and energy eliminates the disease.

Clinical Signs and Differential Diagnosis

The course of oak toxicosis usually is 1 to 12 days, but some cattle have a protracted, debilitating disease.^854,855 In the peracute stages cattle are recumbent, weak, anorectic, and listless.⁸⁵⁴ The rectal temperature is normal or below normal, and the heart and respiratory rates are elevated. Marked edema is present in the perineum and vulva (Fig. 32-105), and edema is obvious in the submandibular area, brisket, and ventral abdomen. Hydration appears adequate, but anuria is present. Firm, dark, mucus-covered feces usually are present. Evidence of hydrothorax, hydropericardium, and ascites may be noted on physical examination. Some cattle may simply be found dead.

Fig. 32-105 Perirectal and vulvar edema in a 3-month-old calf with acute oak bud toxicity. Acute acorn or oak poisoning causes similar lesions.

A day or two after ingestion the animals appear anorectic and listless and have decreased ruminal motility. Many calves have hemorrhagic diarrhea or dark diarrhea that tests positive for fecal occult blood. The feces may have a smell of phenol. Dehydration occurs rapidly, but vital signs may be remarkably normal until hypovolemia develops. As uremia progresses, scleral vessels become dark and engorged, and the breath may take on the smell of ammonia. The major differential diagnoses are other causes of renal failure and other toxins and clostridial diseases; viral diseases that cause ulceration of the alimentary tract should also be considered. Protracted cases most often result from renal failure and uremia, although some animals have chronic oral, esophageal, or gastrointestinal ulceration or perforation with abscessation.

In horses signs usually are peracute or acute; they include sudden death or colic, tenesmus, and hemorrhagic diarrhea.⁸⁵⁶ Acorn husks and shells may be noted in the feces. As with most colics, tachycardia, hyperpnea, and injected oral mucous membranes are seen. Increased abdominal borborygmi often are present, and hemoglobinuria may occur. Determination of serum or urinary phenolic (hydrolyzed tannin) content, based on a gallic acid standard, may be used in acute cases.⁸⁵⁶

Clinical Pathology

In cattle with peracute and acute signs, the serum urea nitrogen and creatinine are elevated, whereas other laboratory values may show considerable variation.^855,856 Initially hyponatremia, hyperkalemia, hypochloremia, hyperphosphatemia, and a marked hypocalcemia (5.1 to 6.8 mg/dL) accompany a mild metabolic acidosis with a very high anion gap (29 to 32).⁸⁵⁴ Neutrophilia with mild hyperfibrinogenemia may be present. Although sorbitol dehydrogenase and GGT may be elevated, biopsy does not indicate that significant hepatic disease occurs with oak toxicosis. Animals may be anuric. If urine is being produced, often isosthenuria, proteinuria, and glucosuria occur. The urinary fractional excretion of sodium was elevated in one steer.⁸⁵⁸

In protracted cases the major findings are elevated serum urea nitrogen, creatinine, and anion gap, with variable hyponatremia, hypokalemia (versus hyperkalemia in acute stages), hypochloremia, and hyperphosphatemia. A mild metabolic alkalosis may be present. Hyperfibrinogenemia and an increase in total plasma proteins also are variable. An elevated WBC count most often reflects chronic ulceration or abscessation (neutrophilia or monocytosis or both). Liver enzymes usually are normal in protracted cases. Urinalysis results are similar to those in acute cases; in addition, hematuria often is present. By 6 weeks after exposure, a normocytic, normochromic anemia may develop as a result of chronic inflammation and uremia, and hypoalbuminemia may result from chronic renal and gastrointestinal losses. By 8 weeks after exposure, surviving cattle have largely returned to normal renal function as determined by normal serum urea nitrogen and creatinine concentrations and by the ability to concentrate urine after a 24-hour water deprivation test.⁸⁵⁴

Laboratory findings in horses are similar to those in ruminants, except that during the acute stages rapid hemoconcentration and marked increases in PCV occur.⁸⁵⁶ Although protein, occult blood, and hemoglobin casts have been reported to be present in the urine, the urine specific gravity was 1.052.

Pathophysiology

The toxicity of oak is attributed to its high concentration of tannins, which are hydrolyzed in the rumen to gallic acid, pyrogallol, and other compounds. The tannins themselves may contribute to oral, esophageal, and gastrointestinal damage by binding to proteins, including those in epithelial cells. This results in oral, esophageal, and ruminal ulcers or perforations. Protein-bound tannins are liberated in the acidic abomasum, making them available once again to damage intestinal epithelium. Some hydrolyzed tannins are absorbed and bound to plasma proteins and endothelial proteins, resulting in hemorrhage and fluid loss from the vascular compartment into body cavities and tissues; this results in edema. The gallic acid and pyrogallols are extremely toxic to renal tubules, causing acute tubular necrosis, anuria, electrolyte abnormalities, and uremia. Ruminants are more susceptible than horses because of the hydrolysis of the gallotannins in the rumen.

Epidemiology

Young cattle in the 100- to 300-kg range seem to be particularly susceptible. In the southwestern United States oak toxicosis accounts for considerable economic loss in cattle.⁸⁵⁸ The disease is seen sporadically in other ruminants and in horses. The morbidity rate in cattle varies considerably, with several to many calves in a pasture usually affected, and case fatality rates frequently exceed 80%.⁸⁵⁵

The disease is most often associated with ingestion of acorns in the fall and buds or young leaves in the spring. Cattle turned onto a pasture with oak trees under which acorns have accumulated may have toxicosis even when adequate forage is available.⁸⁵⁵ In other cases windstorms have dropped numerous acorns or branches in a pasture to which cattle were already accustomed. In the early spring a heavy, unseasonable snowstorm may occur, covering the grass and bending young trees and breaking branches so that oak buds and young leaves are accessible.⁸⁵⁴ Young leaves and acorns are more palatable than older leaves and also contain more tannins (up to 10% dry matter in acorns). The seedlings, buds, and acorns of small scrub oak may be important forages for cattle in parts of the United States.⁸⁵⁸

Necropsy Findings

In peracute and acute cases prominent edema is often the most striking lesion. Ascites, hydrothorax, hydropericardium, perirenal edema, and subcutaneous edema are found. The kidneys are normal in size with multiple diffuse hemorrhages on the surface and extending into the cortex. The liver is slightly swollen and pale or mottled. Digestive tract lesions vary from congestion to hemorrhage and deep ulceration or perforation with necrotizing inflammation. Mucosal ulceration is found in the pharynx, esophagus, rumen, abomasum, small intestine, cecum, and colon. Free blood or melena may frequently be observed.

Diffuse renal tubular damage is present. The changes include coagulation necrosis of cortical tubular epithelium and dilated tubules devoid of epithelium but with intact basement membranes. Many medullary tubules contain hyaline, granular, or cellular casts. The principal renal lesion is necrosis of the proximal convoluted tubules, but glomerular degeneration and fluid in Bowman’s capsules are also seen.

By 3 to 6 weeks after exposure, the lesions include gastrointestinal ulceration, often with secondary infection; some healed ulcers; secondary bacterial bronchopneumonia; and slightly swollen, pale brown kidneys. Histologically, atrophy of the cortical tubular epithelium with a marked interstitial fibrosis and mononuclear infiltrate is seen. Evidence of tubular epithelial regeneration may be present. The liver appears normal.

Treatment and Prognosis

In acute stages intravenous fluid therapy aimed at promoting diuresis and correcting acid-base and electrolyte abnormalities may be lifesaving. Calcium, sodium, and chloride deficits should be replaced, and sodium bicarbonate should be given if needed to correct metabolic acidosis. In anuric animals furosemide (1 mg/kg given IV) can be administered every 12 hours, along with adequate fluid therapy. Corticosteroids and NSAIDs are not likely to have a measurable effect on the course of the disease because they are unlikely to alter the direct toxic effects of the toxic metabolites. The prognosis is guarded and must be considered poor in animals that remain anuric despite therapy. The case fatality rate undoubtedly depends more on the amount of toxic material ingested than on therapy. Antibiotics, given to prevent secondary pneumonia and abscessation, ruminal transfaunation, and readily accessible grass hay and water are recommended components of nursing care.

If the animal survives the acute stage and begins to eat voluntarily, the prognosis for recovery is good unless secondary pneumonia or gastrointestinal abscessation after perforation occurs. Renal function can return to normal by 5 to 10 weeks, and weight gains as high as 1.76 kg/day may be recorded in recovered cattle.⁸⁵⁴

Colicky horses can be treated as one would usually treat colic (intravenous fluids, analgesics, oral laxatives). Particular attention should be paid to diuresis, acid-base balance, and maintenance of serum calcium levels.

Prevention and Control

No specific antidote exists for oak toxicosis, but supplementation with calcium hydroxide (hydrated lime) immediately before anticipated exposure to oak has been effective under experimental conditions.⁸⁵⁹ Feed containing 10% or less calcium hydroxide is palatable. Consumption of 0.9 kg/head/day of cubed or pelleted supplement containing 10% hydrated lime is effective in preventing toxic manifestations.

Supplementation of cattle suddenly exposed to oak with any feed reduces death losses, apparently by allowing hungry cattle to consume the supplemental forage preferentially.^854,859 In an outbreak in California caused by spring snows in which 2700 cattle died of oak toxicosis, ranches where hay was immediately supplemented had minimum losses compared with ranches where feed supplementation was not offered.

Definition and Etiology

Winter dysentery is an acute, contagious diarrheal disease of cattle that occurs in epizootic fashion in a herd, usually during the colder months of the year. It is usually recognized by the clinical syndrome that occurs in herds and by exclusion of other causes of contagious diarrhea.⁸⁶⁰ In the United States the disease is more common in the northern states; however, it has been reported in Australia, Sweden, the United Kingdom, Israel, France, Belgium, Japan, and Canada. The period of illness in an individual is brief, and within a herd the outbreak usually lasts less than 2 weeks. Recovery is spontaneous in most individuals, but in some cases supportive therapy may be indicated. The morbidity rate may be high in a herd that has not experienced winter dysentery for several years; regardless, mortality usually is rare. Although most reports indicate this to be a disease of adult cattle, in a herd outbreak mild diarrhea may be observed in animals as young as 4 months old.

There is still uncertainty regarding the precise cause of winter dysentery, but most recent attention has focused on a coronavirus that may be the same as or related to the coronavirus that causes diarrhea in neonatal calves. In Japan, France, Belgium, and the United States, investigators have identified a coronavirus or similar virus particle in the feces of cattle with winter dysentery.^861-866 The disease was reproduced by contaminating feed with untreated feces in one of two attempts.⁸⁶¹ By immune electron microscopy, antigenic cross-reaction has been demonstrated between the original Nebraska calf coronavirus diarrhea agent and coronavirus isolated from field outbreaks of winter dysentery.^863,865 A rise in serum antibody titer to the calf coronavirus after an outbreak of winter dysentery in adult cattle was found.⁸⁶³

Clinical Signs and Differential Diagnosis

Winter dysentery is an explosive diarrheal disease accompanied by some degree of anorexia and depression. In lactating cows, milk production is reduced. In rare cases mild colic may be observed; other animals may appear weak and prefer to lie down. If the diarrhea is severe or persists longer than a day, dehydration may develop. Weight loss is apparent and is caused by loss of ruminal fill and depletion of extracellular fluid. Ruminal motility usually is reduced, but intestinal borborygmi may be increased. Thirst often is increased, and polydipsia follows the diarrhea. Rectal examination may reveal dilated intestinal loops. The feces vary from light tan to dark brown; bubbles commonly form in the puddles that are deposited several feet behind the cow. Blood may be present in the feces of several animals in a group, typically in the first lactation heifers. The amount of blood may range from just visible to large clots, or it may be uniformly mixed into the feces. Some animals may have thick mucus in the feces. The odor in a barn during an outbreak of winter dysentery has been described as musty, fetid, and sweet and nasty.⁸⁶⁷

Fever usually is not present during the diarrheal phase of the disease but has been reported to precede it⁸⁶⁰ or have no consistent relationship.⁸⁶⁸ Mild respiratory signs consisting of serous nasolacrimal discharge and a soft cough have been inconsistently observed before diarrhea. Diarrhea caused by BVDV, coccidiosis, and salmonellosis must be considered in the differential diagnosis of winter dysentery. With winter dysentery no mucosal lesions are visible on physical examination. The absence of coccidial oocysts or parasite ova in the feces helps exclude these agents as responsible for the diarrhea. However, diarrhea caused by parasites may precede the shedding of detectable organisms in feces. The rapid occurrence of multiple cases within a herd, and often within herds in a locality, suggests winter dysentery. Fecal culture for Salmonella yields negative results in uncomplicated cases of winter dysentery.

Clinical Pathology

No consistent hematologic changes that would be of diagnostic benefit have been observed. If significant dysentery persists for longer than a day, signs of anemia may develop.

Pathophysiology

If the current contention that a coronavirus or coronavirus-like agent is causal in winter dysentery is correct, the pathophysiologic characteristics of the disease can be attributed to lesions of the colonic mucosa.⁸⁶⁴ Epithelial cells of colonic crypts are destroyed by viral action, leading to necrosis and hemorrhage. Even though histologic changes have been observed only in the colonic mucosa, blood was observed from the distal duodenum aborally in cattle that died of winter dysentery.⁸⁶⁶ Loss of intestinal mucosal epithelium from colonic crypts leads to transudation of extracellular fluid and blood. The exact mechanism leading to the voluminous, watery diarrhea has not been clarified but may be related to the inflammatory nature of the disease. Mediators of inflammation may lead to hypersecretion in the small intestine and colon.

Epidemiology

The incubation period is thought to be 2 to 8 days. The most susceptible animals are first and most severely affected. In a small, housed herd, the typical incidence of diarrhea during an outbreak begins with the explosive appearance of signs in 10% to 15% of animals on the first day. The second day another 20% to 40% are affected. On subsequent days similar proportions become ill. By the end of a week the first affected animals are completely recovered, and only a few new cases occur. Typically within 2 weeks of the onset of diarrhea, all animals have recovered. This period is marked by significant reduction in milk production. In large herds the outbreak may be prolonged for 6 to 8 weeks. Animals in their first lactation usually are most severely affected, but other cattle recently fresh or otherwise stressed may also have a longer clinical course. This scenario is typical of a herd that had not experienced an epizootic of winter dysentery during the preceding few years. In some herds milder outbreaks occur annually, with fewer animals showing diarrhea and with less severe clinical signs.

Treatment and Prognosis

Most animals with winter dysentery recover spontaneously in a few days without specific treatment. Many palliative treatments have been recommended and used over the years, including intestinal astringents, protectants, and adsorbents. On the basis of 30 years of observations, Roberts⁸⁶⁹ considered none of these treatments to alter the course of the disease. Provision of adequate fresh water, palatable feed, and free-choice salt is the most useful nonspecific therapy. The occasional animal with prolonged or severe dysentery may need a transfusion of 4 to 8 L of whole blood.

Definition and Etiology

Salmonellosis is one of the few diseases that are increasing in prevalence. According to one study, 75% of dairies sampled in California had evidence of Salmonella infection.⁸⁷⁰ A recent multistate study found that 56% of dairies sampled contained cows shedding Salmonella in feces.⁸⁷¹Salmonella of concern for livestock fall mainly into one species, Salmonella enterica, with numerous serovars or serotypes, such as S. enterica serovar Typhimurium, with the words serotypes and serovars used interchangeably. We shorten it to Salmonella Typhimurium by convention. More than 2200 Salmonella serotypes (serovars) have been identified, and many are potential animal and human pathogens. Multidrug-resistant Salmonella Typhimurium DT104 and Salmonella Newport are particularly virulent to animals and human beings. The presence of identical strains of Salmonella Newport among bovine and human isolates indicates that zoonotic transmission is likely.⁸⁷² Fortunately 10 serotypes of Salmonella in serogroups B, C, D, and E are responsible for most disease in cattle; therefore control programs can be aimed at these. Table 32-22 lists the serotypes most commonly isolated from ill cattle in 2006 in the United States.⁸⁷³ Salmonella organisms are gram-negative enteric bacteria that are facultative intracellular parasites. Most serotypes are non—host-specific, but a few are host-adapted. Salmonella Dublin is host-adapted to cattle, Salmonella Abortus ovis, and Salmonella Arizonae to sheep, and Salmonella Abortus equi to horses. Host-adapted serotypes are found most often in their host species, where true long-term carriers exist.⁸⁷⁴ In contrast, non—host-adapted serotypes rarely achieve carrier status and usually infect an animal for a period of 3 to 16 weeks before infection is cleared,⁸⁷⁴ although one cow with multidrug-resistant Salmonella Newport excreted the organisms for 190 days.⁸⁷² Infection with either host-adapted or non—host-adapted serotypes can be symptomatic or asymptomatic, depending on the dose, the virulence of the serotype, and the host’s immune status. There appears to be an association between an increased incidence of Salmonella infections and intensive management practices such as large farms, crowded conditions, and high-protein diets. In the absence of carriers, chain infections and persistence of Salmonella in the environment are responsible for long-term persistence of a given strain on a given dairy.⁸⁷²

Table 32-22 Most Frequently Identified Salmonella Serotypes from U.S. Cattle from July 2005 Through June 2006

Courtesy Dr. Brenda R. Flugrad, APHIS, USDA, NVSL, Ames, IA.

Salmonella are grouped into serogroups (A to Z and 51 to 65), depending on their cell wall antigens (somatic antigens that comprise specific oligosaccharides, often called O antigens, LPSs, or endotoxin). Thus, for example, local and regional laboratories often report that an isolate is a group D Salmonella. The most common group D isolate of cattle is Salmonella Dublin. Final confirmation that the Salmonella isolated is indeed Salmonella Dublin comes from the National Veterinary Services Laboratory in Ames, Iowa, or from some other laboratory in which antisera and facilities exist for identification of all 2200 serotypes on the basis of flagellar (H) antigens and somatic (O) antigens. Some serotypes also express capsular (Vi) antigens composed of mucopolysaccharide. Identification of the serotype is important in planning control strategies. In addition to the serotypes listed, lambs may be infected with Salmonella Arizonae, which comes from several different serogroups. Salmonella organisms are relatively easy to culture from the feces or tissues of infected animals, using common enteric agar such as XLT4 or brilliant green (BG) agar, with tetrathionate and selenite as selective enrichment media.

Clinical Signs and Differential Diagnosis

Salmonella infection can cause a variety of clinical signs. The most common signs are fever and diarrhea⁸⁷⁵ after an incubation period of 1 to 4 days after exposure or a recrudescence from the carrier state. Animals of all ages may be affected, but serious illness is observed most frequently in very young animals and parturient dairy cattle.

The character of the diarrheic feces varies from watery to mucoid with fibrin and blood. Sheets of fibrin may appear to be sloughing mucosa. The feces often have a putrid, foul odor because of the presence of plasma proteins associated with severe IBD. Salmonellosis causes an acute protein-losing enteropathy. The systemic effects of endotoxins (and other toxic material) absorbed through the damaged bowel mucosa may be severe (fever, anorexia, depressed attitude, shock).

Bacteremia may occur rapidly, especially in neonates infected with Salmonella Dublin, Salmonella Typhimurium, or Salmonella Newport. Peracute to acute septicemia in calves may produce lesions in many organ systems. Affected calves usually are under 2 months of age (the range is 1 day to 6 months). Dyspnea, respiratory symptoms, sudden death, and occasionally diarrhea are the principal signs of Salmonella Dublin infection, the incidence of which usually peaks in 6-week-old calves. Blood culture results frequently are positive. Pure cultures of Salmonella Dublin often can be grown from specimens from the lungs of 4- to 8-week old calves with pneumonic (septicemic) salmonellosis. Calves infected with Salmonella Typhimurium are only 14 days of age on average (the range is 1 to 35 days) and have mainly enteric lesions, including enlarged mesenteric lymph nodes, abomasitis, fibrinonecrotic plaques in the ileum, and hemorrhage of Peyer’s patches.⁸⁷⁶

Dry gangrene of the extremities may occur in calves after Salmonella infection, particularly with Salmonella Dublin. Legs, ears, and tails are most commonly affected, and cold agglutinins are suspected to be involved.⁸⁷⁷

In adult cattle, diarrhea or abortion may occur.⁸⁷⁴ Abortion may occur by two mechanisms, because both culture-positive and culture-negative fetuses and placentae may be found in an outbreak. In the former, bacteremia in the dam results in infection of the placenta or fetus, with resulting fetal death and expulsion. Bacteremia and endotoxemia associated with diarrhea and damaged gut mucosa in cattle may result in release of PGF_2α and subsequent lysis of the corpus luteum. Abortion follows in 2 to 3 days, and the fetus and placenta will have culture-negative findings. When the fetus has a culture-negative finding, many other causes of abortion must be considered. Many infectious agents that infect only the dam can act similarly to cause luteolysis and abortion.

Differential diagnoses for the enteric form of salmonellosis in neonates include all the common enteropathogens of neonates: E. coli, rotaviruses and coronaviruses, clostridia, cryptosporidia, and other forms of coccidia. Concurrent infection with these agents is common. In older animals outbreaks should be differentiated from those caused by BVD, winter dysentery, and feed-induced indigestion. Pneumonic and bacteremic salmonellosis in 4- to 8-week-old calves must be differentiated by culture from pneumonic pasteurellosis; in goats, from mycoplasmal infection; and in lambs from septicemic pasteurellosis.

Clinical Pathology

Salmonella enteritis often results in changes in the hemogram,⁸⁷⁸ as effects of endotoxin manifest.⁸⁷⁹ Plasma fibrinogen frequently is elevated because of the inflammatory nature of the disease, and either neutrophilia or neutropenia may be seen. In severe cases a left shift may be present. Initial dehydration may result in an elevated PCV and plasma protein level. The plasma protein level often drops over a period of days as protein is lost into the bowel lumen. Many other nonspecific abnormalities in clinical chemistry values are often seen, including elevated liver enzymes, decreased plasma calcium, and indications of prerenal azotemia if dehydration occurs.

Definitive diagnosis of salmonellosis requires culture of the organism from feces, blood, or tissues. PCR is also available. Serologic evaluation to confirm the development of anti-Salmonella antibodies is useful⁸⁸¹ but is not commonly performed and is not currently available in most laboratories.

Pathophysiology

Salmonellae are invasive organisms that may penetrate ocular, nasal, oral, or intestinal mucous membranes. Salmonella infection is most often transmitted by fecal-oral contamination from livestock or rodents, or by feeding of contaminated protein source animal byproducts (e.g., fish meal, meat meal, bone meal, or feather meal, 40% of which are contaminated in the United States) or contaminated forages or plant proteins such as soybean or cottonseed.

Once eaten, salmonellae attach to mucosal cells, probably by means of a nonfimbrial adhesion.⁸⁸¹ Attachment is increased if gastrointestinal stasis is present or the normal competitive flora has been disturbed. Salmonellae cause degeneration of nearby cells and penetrate both through microvilli and through tight junctions between cells.⁸⁸² The bacteria pass through the enterocytes to the lamina propria, where they stimulate an inflammatory response and are engulfed by macrophages and neutrophils.⁸⁸³ Intracellular bacteria reach regional mesenteric lymph nodes or beyond. The organism has a predilection for lymphoid tissues and is found in highest numbers in Peyer’s patches and mesenteric lymph nodes.⁸⁸⁴ Thrombi form in vessels, and tissue damage can be severe. Virulent salmonellae are capable of surviving in host tissues and multiplying, often as facultative intracellular parasites in macrophages and reticuloendothelial cells.⁸⁸⁵ In the case of carrier animals, salmonellae survive in cells in the presence of high titers of specific extracellular (i.e., serum) immunoglobulins. Intracellular salmonellae can also avoid many antimicrobial drugs and complement. Stress may cause a latent infection to recrudesce, resulting in fecal or mammary gland shedding or clinical disease.

The cell wall of all gram-negative bacteria contains LPS as a component. LPSs are also called endotoxins, and they are extremely biologically active, setting off an immunologic cascade of events that can lead to leukopenia, fever, anorexia, and eventually shock and death.⁸⁷⁹

Epidemiology and Control

A study of calves in California found that 18% of 1-day-old calves shed Salmonella, but this percentage declined rapidly over the first 11 weeks of life. Farms that received calves from other sources were 35 times more likely to have calves that were shedding Salmonella in feces than were closed herds.⁸⁸⁶ Infection with host-adapted Salmonella serotypes may occur as a cyclic endemic disease, especially in calves when Salmonella Dublin is involved. Salmonella infections on a farm are maintained by (1) carrier animals shedding Salmonella Dublin in the feces⁸⁷⁴ or milk,⁸⁸⁰ (2) chain infections in infected calves and cows, (3) rodents, and (4) environmental contamination. Salmonella carriers infected with a host-adapted serotype such as Salmonella Dublin may shed constantly or intermittently. Cattle with the highest risk of becoming Salmonella Dublin carriers are heifers infected between 1 year of age and first calving and cows infected in the parturient period,⁸⁸⁷ but calves surviving Salmonella Dublin infection and illness may also become carriers. Infected carriers that are not shedding are called latent carriers; stress may cause shedding in feces or milk to recrudesce. A single infected, asymptomatic fecal shedder may produce one billion Salmonella Dublin organisms per day to contaminate the environment (one million organisms per gram of feces). Unlike other serotypes, Salmonella Dublin may be carried as a chronic gut and mesenteric lymph node infection and passed in feces or carried as an intramammary infection and passed in contaminated milk.

Calving areas must be constantly cleaned and disinfected between calvings. Raw milk feeding to calves may be a source of Salmonella (100 to 100,000 organisms per milliliter of milk).⁸⁸⁰ Infected calves constantly amplify the number of organisms in the environment, causing exposure of other calves. Calves with clinical signs may shed billions of Salmonella into the environment daily.

Environmental contamination can be difficult to eliminate, because salmonellae survive for months in moist areas out of direct sunlight and in lagoons and drainage areas. Salmonella Dublin was recovered from feces dried for 41 months.⁸⁸⁸ Freezing feces at −20° C (−4° F) kills 85% of salmonellae in 2 days and over 95% by 1 month.⁸⁸⁹ Direct sunlight and drying in hot weather are effective at eliminating salmonellae.

Research has documented contaminated irrigation water as an important source of Salmonella organisms. In some cases municipal sewage treatment plant effluents had contaminated water.⁸⁹⁰ On one dairy farm, river water used to sprinkler irrigate green chop contaminated the green chop, which was fed to cows. On another farm, Salmonella-contaminated river water was used to irrigate cotton. When the cottonseed from that gin was used as feed, cattle became infected. On a third dairy, contaminated irrigation water resulted in haylage containing Salmonella organisms.⁸⁹¹

Feedlot cattle colonized by Salmonella organisms could pose a public health risk when meat is contaminated at slaughter. In a study by NAHMS, 7.5% of cattle on feed the longest shed salmonellae, whereas 3.5% of cattle that had recently entered the feedlot were shedding salmonellae in the feces.⁸⁹² Contamination of the animals before entry can cause the entering cattle to have a higher rate of shedding than was found in cattle that had been in the feedlot for several months⁸⁹³ Standing water contaminated with feces is frequently highly contaminated with Salmonella; culture of temporary shallow lakes (called playas in the southwestern United States) yielded numerous Salmonella serotypes.⁸⁹⁴ In one study 1.4% of cattle, mostly from dairies, shed salmonellae when in a veterinary clinic,⁸⁹⁵ whereas I have found an average of 7% of cattle (mainly dairy cows) in our large animal clinic are shedding Salmonella.

Control of Salmonella infection requires an integrated herd approach. Sick pens were found to be 7.4 times more likely to yield Salmonella as were pens of preweaned calves.⁸⁹⁶ Management interventions that were found effective in helping control Salmonella on dairy farms include separation of sick and parturient cattle into hospital and maternity pens respectively (considered the most important and effective intervention), switching from a phenolic disinfectant to a peroxygen biocide such as Virkon S for equipment disinfection, use of separate footwear or footbaths for personnel in the hospital and maternity pen sections, strict protocols for disinfection of hands and equipment between handling each sick or periparturient cow, strict separation of feeds used in the hospital and maternity pens, and use of clean bedding in the hospital and maternity pens.⁸⁷² To detect herds infected with Salmonella Typhimurium or other serotype except Salmonella Dublin, a herd serologic profile based on ELISA can be used.⁸⁹⁷ Rectal swab sampling and culture of cull dairy cows was found not to be a satisfactory method of detecting Salmonella-infected herds.⁸⁹⁸ To control Salmonella Dublin, carrier cows and calves over 6 months of age are identified by serologic testing (ELISA) for anti-Salmonella antibody.^880,899-901 Suspect animals are culled or tested further by serologic means or by multiple fecal cultures and milk cultures (five samples at weekly intervals). Animals with positive test results are culled. In infected herds, Salmonella Dublin carriers (fecal or mammary) usually make up 0.4% to 3% of a dairy herd. Animals that remain seropositive over a 2-month period should be considered carriers, even if a culture result is negative on five samples.⁸⁸⁰ A Danish study⁹⁰² found that only 14 of 31 persistently seropositive animals were culture positive for Salmonella Dublin at postmortem examination, and one seronegative animal was culture positive. One study found that ELISA serology had a good negative predictive value for cattle 100 to 300 days of age, whereas fecal culture had a poor predictive value.⁹⁰³

To control all non—host-adapted and host-adapted serotypes of Salmonella, calves and cows are promptly treated when signs of illness occur, and strict procedures to prevent the spread of infection are instituted. A study of 14 farms infected with Salmonella Typhimurium DT104 showed that clinical disease ceased by 4 months, but widespread infection and contamination continued. Over time the number of infected farms gradually declined, and vaccination correlated positively with a herd remaining free of clinical illness from DT104.⁹⁰⁴ Control measures include the use of separate feeding utensils for each calf, washing of boots and hands by calf raisers between calves, isolation of ill calves to noncontact pens, and thorough disinfection of pens between calves. Decontamination of pens is most effectively accomplished if an all-in, all-out system is used. Pens are divided into four groups, with each group of pens used for calves born during a given week. When 3- to 4-week-old calves leave their pens as a group, these pens are cleaned and disinfected with a chlorine product such as bleach, a peroxygen product such as Virkon S, or a phenylphenolic disinfectant. This helps prevent continuous recycling of bacteria to each group of new calves. Environmental monitoring by frequent swab cultures of pens is the best way to check the effectiveness of the sanitation and disinfection program. Infection with Salmonella Typhimurium and other non—host-adapted serotypes most often occurs as an epidemic after the organisms enter the farm by means of purchased cattle, rodents,⁹⁰⁵ rendering trucks, or feedstuffs. Even Salmonella Dublin may be maintained on a farm by mice.⁹⁰⁵ A case control study of farms infected with Salmonella Typhimurium DT104 found that the most effective interventions included purchasing cattle directly rather than through a sales yard, quarantining purchased cattle for 4 weeks, housing sick cattle in dedicated isolation areas, and preventing wild bird access to feed storage areas.⁹⁰⁶ Feeds may be contaminated by irrigation water,⁸⁹¹ in manufacturing when byproduct ingredients contain Salmonella organisms, on the farm, or in shipment by birds or rodents or contaminated trucks. When an epidemic involving an exotic serotype occurs, feedstuffs should be examined as a likely source. Exotic serotypes are Salmonella from serogroups other than B, C, D1, and E1; that is, all those groups not listed inTable 32-22. Feedstuff contamination with the serotypes not considered exotic may also occur. High-protein supplements, rumen bypass protein, or calcium-phosphorus supplements of animal origin are sources of epidemics of various Salmonella serotypes in livestock. Forty percent of all animal byproduct feedstuffs in the United States are contaminated with Salmonella organisms. Once a Salmonella serotype enters a herd, the bacteria are rapidly spread among livestock and into the environment, where they may cause a prolonged course of herd illness and can be difficult to eliminate. Such appeared to be the case with Salmonella Newport and Salmonella Montevideo in dairy cattle in California in the past (Table 32-23). These and other group C Salmonella species tend to become endemic and persist for years on a dairy farm once it has become infected. Culture of feeds before use on a farm currently is the only means of preventing the introduction of exotic Salmonella serotypes, because national and international controls currently appear to be inadequate.

Table 32-23 Changing Incidence of Salmonella Serotypes on California Dairy Farms as Illustrated by the Percentage of Farms from Which each Serotype was Isolated in 1985 to 1986 Compared with 1987 to 1988

Blanchard P, Anderson M: Unpublished data based on calves brought for necropsy from Tulare area farms, 1988.

Vaccination

Control by vaccination of dams using killed bacterins may be somewhat beneficial in protecting neonates under 3 weeks of age through colostral and milk immunoglobulin. Because most dairy calves are taken from their dam and fed milk replacer after day one to day 3 of age, the potential benefit of intraluminal milk antibody from the dam is lost. This may account in part for the fact that vaccination of cows by itself often is insufficient to protect calves from salmonellosis. In neonates over 3 weeks of age, colostral immunity appears to play only a small role in protecting against salmonellosis. Because both humoral and cell-mediated immunity are important in protecting against salmonellosis,^907-909 active immunity is superior to passive. Modified live, genetically altered vaccines that stimulate humoral and cell-mediated immunity offer better protection for calves.^909,910 Modified live vaccines have been available in Europe for years. Such a vaccine recently became available in the United States.* The role of increased nonspecific immunity to gram-negative core antigens (through immunization with rough mutants of E. coli and salmonellae lacking complete cell walls) is being investigated. Some studies have been able to demonstrate an increased survival rate for salmonellosis after vaccination with a mutant stain of E. coli (J5),⁹¹² designed to produce antibodies to the common core antigens of gram-negative bacteria. Endovac-Bovi (Re mutant Salmonella) is marketed with the same goal.

Available commercial Salmonella vaccines are killed whole cell bacterins for use in cattle, and a new genetically altered modified live Salmonella Dublin vaccine for calves.* Some practitioners report that they have used the live vaccine orally and found it to be effective but with fewer adverse reactions than when used parenterally. The only products that are solely Salmonella vaccines contain Salmonella Typhimurium or Salmonella Typhimurium and Salmonella Dublin or live Salmonella Dublin organisms (see Chapter 48). Autogenous bacterins can be made for serotypes not commercially available when they are isolated from animals on a farm and believed to be the causative agent of disease. A new subunit vaccine with siderophore receptor protein (SRP vaccine) is being marketed by AgriLabs under conditional USDA license. Siderophores are iron chelating proteins produced by all Salmonella, so producing antibodies against SRPs from Salmonella Newport should theoretically be effective for all serotypes of Salmonella, and because they are a subunit, they should be less toxic.

A major problem associated with Salmonella bacterins and modified live Salmonella vaccines is adverse reactions. Adverse reactions vary from fever, depression, and anorexia to collapse and death after vaccination. Animals may have severe reactions after the first, second, or third dose. The apparent cause of these severe reactions is a high degree of sensitivity to the presence of gram-negative endotoxin, which results in a rapid immune cascade leading to shock.⁸⁷⁹ This sensitivity is genetically controlled, possibly accounting for the high frequency of adverse reactions in one herd and their absence in a neighboring herd. High ambient temperatures also increase sensitivity to the adverse effects of endotoxin. Adverse reactions usually can be reversed by using epinephrine (1 mL of 1:1000 [1 mg/mL] for every 50 kg of body weight given IM or IV) as soon as evidence of polypnea, dyspnea, or weakness appears.

Lack of efficacy of killed Salmonella bacterins in calves is evident in experimental studies. Commercial bacterin vaccines in aluminum hydroxide administered directly to calves at 2 and 4 weeks of age failed to protect the calves when they were orally challenged at 6 weeks of age.⁹¹² Other research has demonstrated protection in older vaccinated calves that were challenged intravenously.⁹¹³ Calves under 12 weeks of age do not serologically respond with anti-LPS antibodies after vaccination with two or three doses of killed bacterins in aluminum hydroxide.⁹¹⁴ On the other hand, calves over 12 weeks of age and cows do respond serologically to two doses of the same vaccine.⁹¹⁵ The ELISA titer in cows is short-lived (2 to 4 weeks); therefore the timing of vaccination before parturition is critical if the aim is to increase the anti-Salmonella colostral immunoglobulin G titer.⁹¹⁵ Under experimental conditions, calves fed colostrum from vaccinated dams were not protected against oral challenge at 3 weeks of age.⁸⁷⁸ One report suggests that vaccination with killed Salmonella Typhimurium vaccine prevented reinfection and recrudescence of clinical signs after an outbreak of DT104 and helped in eliminating the organism from the farm.⁹⁰⁶ As mentioned previously, these differences may in part be explained by whether or not a calf continues to receive milk from its dam and thus has or does not have intraluminal antibodies. Other live vaccines have been found effective in calves and capable of cross-protection against other serotypes, including a DNA adenine methylase—deficient Salmonella Typhimurium⁹¹⁶ and an avirulent live Salmonella Choleraesuis strain 54,⁹¹⁷ but neither was licensed for cattle in the United States as of 2007.

Necropsy Findings

Treatment

The keys to successful treatment of bacteremia caused by gram-negative bacteria are (1) antimicrobial drugs, (2) fluids and electrolytes, and (3) NSAIDs. Salmonella Typhimurium antiserum is available commercially. Adverse reactions by cattle to horse serum are common; care should be taken.

Early in the course of disease in calves, appropriate antimicrobial therapy often increases the survival rate markedly, because bacteremia frequently occurs. Appropriate antimicrobial therapy depends on culture and antimicrobial sensitivity patterns. Many of the most virulent Salmonella types are now multidrug-resistant, but isolates of relatively nonpathogenic Salmonella on dairies and feedlots found on surveys are usually sensitive to most antimicrobials.^886,918 In general, most Salmonella organisms are sensitive to florphenicol, ceftiofur (and other third-generation cephalosporins), TMS, gentamicin, amikacin, and fluoroquinolones such as enrofloxacin.^885,886 Higher than label doses of ceftiofur used in calves with experimentally induced Salmonella Typhimurium infections did not alter mortality but did reduce fecal shedding and promote more rapid clearance.⁹¹⁹ Sulfas and fluoroquinolones may not be used extralabel in food animals in the United States. Aminoglycosides such as neomycin, gentamicin, and amikacin produce long-term tissue residues and should be avoided in animals intended for use as food. Susceptibility to ampicillin, amoxicillin, sulfas, and tetracycline varies considerably, whereas resistance to penicillin, streptomycin, erythromycin, and tylosin is anticipated. TMS combinations are relatively inexpensive, especially when given orally, but oral TMS should be used only in calves younger than 3 weeks of age. In calves over 3 weeks of age, trimethoprim should be given IV because it is destroyed in the rumen and not absorbed. Antimicrobial drugs such as fluoroquinolones, florphenicol, or TMS that achieve good intracellular levels and have a large volume of distribution appear to be more effective than those that do not achieve good intracellular levels (e.g., gentamicin and amikacin). Florphenicol or cephalosporins such as ceftiofur are good choices for therapy against many Salmonella isolates depending on susceptibility testing results. Antimicrobial drugs may not be effective at altering the clinical course of strictly enteric infections without bacteremia, but because bacteremia frequently accompanies salmonellosis, systemic antimicrobial therapy often is chosen.

The effects of endotoxins can be partially dampened or controlled by the judicious use of NSAIDs. The cascade of events caused by bacterial endotoxin (LPS from the cell wall) must be brought under control early and rapidly, by the use of drugs such as flunixin (Banamine) at a dose of 1.1 to 2.2 mg/kg every 12 hours. Once the animal is stabilized, NSAIDs should be discontinued, as continued administration can lead to adverse side effects such as abomasal ulceration.

Intravenous fluid therapy to maintain blood volume and pressure and correct acid-base or electrolyte abnormalities is important in any animal that is dehydrated or in shock (see Chapter 20, Neonatal Diarrhea, Chapter 32, Equine Fluid Therapy, for adult equine, and Chapter 44 on critical care). Measurement of blood gases and electrolyte values is useful to assist in fluid therapy formulations. Fluids containing sodium, with supplementation of glucose, should be administered intravenously as needed. Metabolic acidosis with mixed water by electrolyte losses is most often seen. Oral fluids and electrolytes may also be effective supplements. The prognosis is good if animals are treated aggressively and early in the course of illness.

Control of Infectious Disease in a Veterinary Hospital

Veterinarians must also be aware of preventing the spread of Salmonella and other nosocomial diseases within an animal hospital and should have an effective written infectious disease control program in place.⁹²⁰ See Chapter 46.

Definition and Etiology

Johne’s disease is an insidious chronic infection of primarily ruminants but also includes rabbits,^921-923 foxes, stoats, weasels, Eurasian badgers, bears, wild boar, brown hare, brown rat, crow, rook, jackdaw, and long-tailed field mouse, among other species. It is caused by Mycobacterium avium subsp. paratuberculosis.^924-932 Despite having 99% DNA homology,^933,934M. avium subsp. paratuberculosis can be differentiated phenotypically from M. avium subsp. avium by its dependence on mycobactin⁹³⁵ and genotypically by the presence of multiple copies of an insertion element, IS900,⁹³⁶ or a single copy of heat shock protein (HSx), among other DNA markers.⁹³⁷ The two major strains of M. avium subsp. paratuberculosis identified by DNA strain typing are the cattle strain (c) and the sheep strain.⁹³⁸ Other strains of M. avium subsp. paratuberculosis, with the exception of the Bison strain, have less species specificity.^939-942

After ingestion of M. avium subsp. paratuberculosis during the perinatal period, the bacteria are absorbed by the M cells of the small intestine and gradually spread to regional lymph nodes.⁹⁴³ Given adequate time, M. avium subsp. paratuberculosis infection becomes systemic, spreading to other body organs including the liver, mammary gland, uterus, pulmonary lymph nodes, and peripheral lymph nodes such as the popliteal and superficial cervical nodes. The term Johne’s disease typically refers to the clinical disease condition with weight loss and diarrhea, whereas the term paratuberculosis refers to the condition of being infected with the causative organism, M. avium subsp. paratuberculosis, but not necessarily having clinical signs.

Clinical Signs

The great majority of infected animals appear clinically normal when compared with herdmates. Only after a prolonged incubation period, typically longer than 2 years and up to 10 years, do infected animals begin to develop subtle clinical signs including gradual weight loss despite a normal appetite and usually decreased milk production. Over a period of several weeks, concurrent with the weight loss, the manure consistency changes to become softer then loose and usually progresses to a pipestream diarrhea without tenesmus. The diarrhea is initially intermittent, with periods of normal manure consistency. Other than the loose consistency, the manure appears normal; blood, excess mucus, and tenesmus are not present during this time, and the animal continues to lose weight despite a normal appetite. In rare cases diarrhea begins suddenly as a persistent loose manure or watery scours. Other than the loose consistency, the manure appears normal. As the disease progresses, affected animals become increasingly lethargic and emaciated. Intermandibular edema and possibly ventral sternal edema caused by hypoproteinemia typify advanced stages of the disease. Cachexia and “waterhose” diarrhea characterize the terminal stages of the disease. Most animals are culled from the herd before this time because of decreased milk production and/or severe weight loss.

Stages of Infection and Disease

Clinical Pathology

Early stages of infection are not associated with any characteristic biochemical or hematologic changes. Animals with clinical signs are typically hypoproteinemic (TPP <5.5 g/dL) with reductions in albumin (<2 g/dL) and all classes of immunoglobulin. The marked muscle loss may be associated with elevated plasma phosphorous levels (up to 10 mg/dL), which is attributed to the catabolic state with phosphorus release resulting from muscle wasting. The animals are often mildly anemic (PCV <25%) with concurrent hypocalcemia (caused in part by the hypoalbuminemia), hyponatremia, and hypokalemia.

Pathophysiology

M. avium subsp. paratuberculosis enters the intestinal tract typically by fecal-oral contamination and is taken up preferentially by the M cells, specialized absorptive cells in Peyer’s patches,⁹⁴³ where the organisms are resistant to intracellular degradation and eventually phagocytosed by subepithelial macrophages.¹⁰⁰⁸ However, recent work would suggest that these organisms may be taken up by absorptive cells throughout the entire length of the small intestine. Typically the organisms proliferate slowly within macrophages in the intestinal mucosa then spread to regional lymph nodes. In the regional lymph nodes the bacteria stimulate inflammatory and immunologic responses.^1009,1010 The elicited response is similar to that to other mycobacterial infections, most importantly T lymphocytes with cytokines from T helper cells. IFN-γ, one of these cytokines, is an important component of the protective host response and may be an early indication of M. avium subsp. paratuberculosis infection.¹⁰¹¹ In some infected cows the cellular response is able to control infection, with the animal never developing clinical signs but remaining subclinically infected for life.^992,1010 Poor nutrition, stress related to transport, lactation, and parturition have been proposed as accelerating or precipitating the onset of the clinical phase of infection.⁹⁹²

The minimum time from infection to the onset of clinical signs requires at least 12 months of heavy and repeated doses of M. avium subsp. paratuberculosis, and small doses of organism may require more than 10 years before clinical signs appear. In heavily infected herds with many clinical cases, yearling heifers may show evidence of ill thrift and loose manure because of Johne’s disease, but this is rare. Typically the first evidence of weight loss and diarrhea occurs within several months of calving or another period of stress. On some occasions noninfected adult cattle become infected as adults when introduced to a heavily infected herd and then develop clinical signs several years later. The infected animal responds to the mycobacterial organism with the recruitment of macrophages and development of giant cells.¹⁰¹² As the organism multiplies over weeks and months, the thickened intestine is less able to absorb nutrients and the animal loses weight despite a normal appetite. The thickened intestinal wall begins to gradually leak protein, mainly albumin, from the blood into the intestine, resulting in a direct nutrient loss from the bloodstream and hypoproteinemia.