CASE NOTES
Mortalities associated with oesophagitis in sheep
Andrew Peters1, Timothy Biffin2, Emma Croser1, Janet Wild1
1 School of Animal & Veterinary Sciences, Charles Sturt University
2 Riverina Local Land Services, Wagga Wagga
Posted Flock & Herd March 2016
Introduction
Oesophagitis is a rarely described pathological finding in sheep. Previously described naturally-occurring cases include ulcerative oesophagitis associated with caseous lymphadenitis and oesophageal compression in a sheep flock in Brazil1, with pythiosis in lambs in Brazil2 and with non-cytopathic border disease virus (BDV) in Switzerland3. Erosive-ulcerative oesophagitis has been observed in sheep inoculated experimentally with intranasal ovine herpesvirus-2 (OvHV-2), one of the viral agents of malignant catarrhal fever4.
Erosive and ulcerative oesophagitis is more commonly seen in other species and typically has either a viral or physical injury aetiology5. Herpesvirus infection is infrequently associated with oesophagitis in animals. Oesophageal ulceration has been reported in goats, bison and cattle infected with OvHV-26-8. Erosive oesophagitis associated with herpesvirus infection has been described in various bird groups, including pigeons, raptors, waterfowl and parrots9-11. Ulcerative or erosive oesophagitis occurs in mucosal disease associated with infection with Bovine Viral Diarrhoea Virus and also the so called “3D syndrome” in cattle is a recognised cause of ulcerative or erosive oesophagitis5,12. Physical injury can occur to the oesophagus through contact with erosive substances, including gastric contents during gastro-oesophageal reflux, as reported in foals13. Mechanical and chemical injury causing oesophagitis is also a recognised, albeit uncommon, condition in dogs and cats14.
This case report documents the gross, clinical and histological presentation of erosive oesophagitis in a group of sheep in central southern New South Wales, most likely following ingestion of a caustic substance.
History and clinical examination
Sudden death was reported in 22 out of approximately 2100 merino crossbred weaner lambs (3-4 months old). Symptoms were rapidly progressive, including weakness, altered mentation, recumbence and inability to rise, preceding death. The majority of cases were found dead and all animals that displayed clinical signs subsequently died or were euthanased. In total, over 30 lambs died in association with this one event.
The mob had been weaned onto a non-irrigated super phosphate treated lucerne pasture with access to dam water. Five days prior to the onset of symptoms, the mob was moved onto 162 hectare dry wheat stubble containing varied amounts of rye grass, present as a crop weed. In this paddock there were no dietary supplements (including minerals) and grain spillage was not identified. The mob had received appropriate multi-valent clostridial and caseous lymphadenitis vaccination and was reported to have been in sound health and body condition when moved onto the wheat stubble. Notably, the mob was driven to the three available dams upon arrival at the stubble paddock.
At the onset of disease, carcasses were scattered with the majority lying along the eastern fence line: the side closest to the lucerne weaning paddock (Figure 1). There was no evidence of external injury, thrashing or paddling surrounding any of the carcasses.
Four animals, displaying similar clinical signs, were clinically examined. The first sheep [sheep 1] was examined one day after the first deaths occurred. This animal was in sound body condition score (2.5/5) stuporous and laterally recumbent with only occasional limb movement. Tachycardia, tachypnoea, pyrexia (41.7°C), reduced gut sounds and moist, pink mucosal membranes were observed. As deaths continued, three more sheep were examined, five days after the onset of deaths. These animals [sheep 2-4], were ambulatory although mentally altered and ataxic (sheep 3 was least affected). Sheep 2-4 also had mild perineal faecal staining. Ptyalism was not observed in any of the animals.
Figure 1. The majority of the sheep found dead with no observed clinical signs were located along the eastern boundary of the affected paddock, which was the side closest to their original weaning paddocks of lucerne. To the right is dry wheat stubble typical for the affected paddock. Photo edited for brightness and contrast.
Clinical pathology
An onsite anthrax immunochromatography (ICT) test was negative.
Blood was collected ante-mortem from all four sheep. Urine was collected from three (sheep 1,3-4) via cystocentesis immediately post-mortem. Haematology, biochemistry and urinalysis were performed (Table 1).
Table 1. Haematological, serum biochemical and urinanalysis parameters in four examined sheep. Serum haemolysis index of '+' indicates mild haemolysis.
| Analyte | Sheep 1 | Sheep 2 | Sheep 3 | Sheep 4 | Reference intervals |
|---|---|---|---|---|---|
| Red blood cell count | - | 16.4 | 14.8 | 9.7 | 10.0-14.2 x1012/L |
| Haemoglobin | - | 168 | 147 | 96 | 99-135 g/L |
| Haematocrit (calculated) | - | 0.37 | 0.35 | 0.27 | 0.29-0.40 L/L |
| Haematocrit (PCV) | - | 0.56 | 0.53 | 0.30 | 0.29-0.40 L/L |
| MCV | - | 23 | 24 | 27 | 25-34 fL |
| MCH | - | 10 | 10 | 10 | 9-12 pg |
| MCHC | - | 451 | 415 | 364 | 323-367 g/L |
| Platelets | - | - | 1024 | 1193 | 372-367 g/L |
| White blood cell count | - | 5.5 | 25.3 | 6.8 | 4.1-13.0 x109/L |
| Neutrophils | - | 3.6 | 19.7 | 5.1 | 0.5-9.3 x109/L |
| Band neutrophils | - | 0.0 | 0.0 | 0.0 | 0.0-0.0 x109/L |
| Lymphocytes | - | 1.5 | 4.3 | 1.5 | 1.1-7.6 x109/L |
| Monocytes | - | 0.4 | 1.3 | 0.2 | 0.0-0.7 x109/L |
| Eosinophils | - | 0.0 | 0.0 | 0.0 | 0.0-0.3 x109/L |
| Basophils | - | 0.0 | 0.0 | 0.0 | 0.0-0.2 x109/L |
| Fibrinogen | - | 13.0 | 12.0 | 14.0 | 3.0-7.0 g/L |
| Total protein | 99 | 94 | 69 | 82 | 60-82 g/L |
| Albumin | 53 | 48 | 20 | 47 | 29-41 g/L |
| Globulins | 46 | 46 | 49 | 35 | 30-42 g/L |
| A:G ratio | 1.2 | 1.0 | 0.4 | 1.3 | 0.6-1.7 g/L |
| Creatinine | 1699 | 764 | 75 | 645 | 44-72 µmol/L |
| Urea | 84.5 | 48.4 | 11.9 | 72.8 | 5.4-11.4 mmol/L |
| CK | 31967 | 1969 | 111 | 1373 | 1-617 U/L |
| AST | 758 | 503 | 71 | 408 | 59-130 U/L |
| GLDH | 25 | 15 | <1 | 9 | 1-23 U/L |
| Glucose (unpreserved) | 38.9 | 16.1 | 8.8 | 10.2 | |
| Glucose (preserved) | - | 10.2 | 7.9 | 9.8 | 2.4-4.5 mmol/L |
| Bilirubin | 5 | 5 | 8 | 4 | 2-3 µmol/L |
| GGT | 63 | 49 | 22 | 46 | 47-95 U/L |
| Potassium | 9.4 | 2.1 | 3.7 | 3.9 | 4.3-5.5 mmol/L |
| Sodium | 188 | 121 | 139 | 117 | 137-148 mmol/L |
| Na:K ratio | 20 | 58 | 38 | 30 | 24.9-33.9 |
| Anion gap | 40 | 23 | 20 | 27 | 12-23 mmol/L |
| Bicarbonate | 11 | 11 | 17 | 8 | 19-32 mmol/L |
| Calcium | 2.7 | 2.78 | 2.24 | 2.58 | 2.81-3.42 mmol/L |
| Phosphate | 6.47 | 0.75 | 0.50 | 3.15 | 1.02-2.67 mmol/L |
| Ca:PO4 ratio | 0.4 | 3.7 | 4.5 | 0.8 | 0.9-2.9 |
| Chloride | 146 | 89 | 106 | 86 | 101-112 mmol/L |
| Magnesium | 1.57 | 1.22 | 0.75 | 0.94 | 0.50-1.50 mmol/L |
| Cholesterol | 4.2 | 3.1 | 0.7 | 1.9 | 1.3-2.0 mmol/L |
| Beta hydroxybutyrate | 0.1 | 0.2 | 0.2 | 0.6 | 0.0-0.9 mmol/L |
| Serum haemolysis | + | + | + | + | |
| Urine specific gravity | 1.038 | - | 1.030 | 1.018 | |
| Urine pH | 5 | - | 6 | 5 | |
| Urine blood | +++ | - | +++ | ++ | |
| Urine protein | +++ | - | + | ++ | |
| Urine ketones | 0 | - | 0 | 0 | |
| Urine bilirubin | 0 | - | Trace | 0 | |
| Urine glucose | 0 | - | 0 | 0 |
All sheep had evidence of azotaemia. Sheep 1, 2 and 4 had moderate to marked panhyperproteinaemia indicative of dehydration, chronic inflammation or antigenic stimuli, while sheep 2 and 4 also displayed moderate polycythaemia, further indicating dehydration.
An increase in CK and AST in sheep 1, 2 and 4 indicates significant sub acute muscle damage.
Hyperbilirubinaemia in all sheep, in the absence of cholestatic liver enzyme elevation is indicative of anorexia. Severe and varied electrolyte abnormalities were observed.
Post-mortem examination
Sheep were euthanased by exsanguination [Sheep 1] or intravenous pentobarbitone [Sheep 3 and 4]. Full post-mortem was performed on the three sheep including removal of the brain. Sheep 2 was not euthanased and only blood was collected for haematological and biochemical examination.
Sheep 1. The oesophageal mucosa was pale and friable. No mural lesions or unusual contents were observed in the lower gastrointestinal tract except for a focal area of discolouration in the jejunum. The liver was mildly pale and friable. The urine was dark yellow-brown. There was no distension of the urinary bladder.
Sheep 3. Enlarged mesenteric lymph nodes and mildly congested intestines. Rumenal pH was 7. There was marked distension of the gall bladder. The oesophagus appeared normal.
Sheep 4. Mild multifocal subpleural pulmonary emphysema (sub acute). The oesophagus had an extensive caseous change to the mucosal surface.
All other tissues and organs examined in the three sheep were grossly unremarkable. Significantly, the rumen contents of all three sheep were moist with reasonable water content.
Histopathology
Multiple tissues from Sheep 1, 3 and 4 were examined histologically following formalin fixation.
Primary histopathological findings in Sheep 1 and 4 included extensive and severe ulcerative oesophagitis with eschar formation (Figures 2-5). Fixed oesophagus for histological examination was not submitted from sheep 3. The rumen and reticulum from sheep 1, 3 & 4, did not exhibit histological abnormalities.
Figure 2. Oesophagitis in Sheep 1, demonstrating marked infiltration of the mucosa and submucosa with neutrophils. H&E stain.
Figure 3. Eschar formation present in the oesophageal mucosa of Sheep 1. In other sections this was associated with full-thickness ulceration of the oesophageal mucosa. H&E stain.
Figure 4. Severe, full thickness oesophageal mucosal ulceration was present in Sheep 4. H&E stain.
Figure 5. Significant formation of eschars had occurred in the oesophageal lumen of Sheep 4. H&E stain.
Further laboratory testing
Laboratory tests were conducted on water samples from each of the three dams in the stubble paddock (Table 2).
Table 2. Electrical conductivity and pH results from water samples obtained from each of the three dams available to the affected sheep.
| Dam name | Test performed | |
|---|---|---|
| Conductivity (µS/cm) | pH units | |
| "G2" | 298 | 7.2 |
| "G3" | 169 | 9.8 |
| "G4" | 178 | 8.0 |
Discussion
All sheep had evidence to support dehydration. Sheep 1, 2 and 4 all seem to be at different stages of the same condition, with sheep 1 in the most advanced stage. Sheep 2 and 4 appeared to be losing sodium-rich fluid. Loss of sodium via the kidneys or lower gastrointestinal tract was unlikely given urine acidity and the lack of histopathologic lesions in these organs. It was more likely that extracellular fluid loss was occurring via the grossly and histologically observed oesophageal lesions.
It is expected that this electrolyte shift would be corrected by intestinal reabsorption, however, decreased ruminal emptying, associated with anorexia, may have been preventing this mechanism. This also explains the contradictory moistness of the ruminal contents observed, despite strong clinical pathological evidence to support dehydration. The rumenal mucosa is capable of absorbing water but not ions, such as sodium; in this scenario hypoosmolarity can develop in the extracellular fluid as electrolyte rich fluid, lost via the oesophagus, is resorbed without its accompanying electrolyte component. Eventually, increasing osmolarity of the rumenal contents would prevent further absorption of water from this compartment against its concentration gradient into the extracellular fluid, leaving the rumenal contents moist despite systemic dehydration.
All sheep had evidence of inflammatory response and hyperglycaemia, which may have been associated with physiological stress. Sheep 1 varied somewhat with particularly elevated glucose. In this animal, elevated potassium and urine specific gravity was likely due to near total cessation of glomerular filtration. Interestingly, in humans, uncorrected mild hyperglycaemia and dehydration can physiologically exacerbate each other, giving rise to severe hyperglycaemia and dehydration in a condition called hyperglycaemic hyperosmolar syndrome16. A similar scenario has been reported in ruminants.17
Sheep 3 had a different clinical pathology profile to the other animals, with a neutrophilic inflammatory leukogram, hyperglobulinaemia and hypoalbuminaemia (most likely due to loss of protein-rich fluid but accompanied by chronic inflammation), only mild azotaemia and no evidence of muscle damage. These clinical pathology findings were suggestive of gastrointestinal disease.
Oesophagitis is very seldom observed in sheep, even as an incidental finding. The ovine oesophageal mucosa consists of keratinised stratified squamous epithelium, presumably as an adaptation to a rough, fibrous diet. Our finding of severe, extensive erosive oesophagitis in two of the three sheep examined by post-mortem during the reported mortality event is likely to be significant and associated with their clinical condition. The severity of the lesions might be expected to cause behavioural avoidance of ingestion.
The clinical pathology findings from three of four affected sheep were suggestive of severe dehydration, and it appears likely from the absence of other specific clinical signs or pathological findings that dehydration would have been the ultimate cause of death in these animals. The pyrexia observed in the first sheep may have been associated with dehydration.
In light of the low serum sodium and chloride levels, it is possible in two of the sheep (Sheep 2 and Sheep 4) that fluid loss contributed significantly to dehydration. Fluid loss into the gut was a significant possibility in these cases, especially in light of the perineal faecal staining seen in these animals. Gastrointestinal lesions responsible for fluid loss in the gut were not obvious in these two sheep on gross and histological examination. Sheep 3, which had significant gastrointestinal lesions and a different clinical presentation, was unlikely to be part of the same clinical picture seen in the other animals. The deaths of the majority of sheep along the fence line closest to their previous paddock may be consistent with water-seeking behaviour (for more familiar water sources), despite the presence of dams in the paddock. It is probable that erosive oesophagitis leading to severe dehydration was the cause of the majority of deaths in the reported mortality event.
Described infectious causes of oesophagitis affecting multiple ruminants are viral. OvHV-2 infection in goats and cattle is almost pathognomonically accompanied by lymphohistiocytic vasculitis and a variety of other gross changes6-8, which were not observed in the three sheep examined histologically. No evidence of viral inclusions, fungal elements or monomorphic bacterial colonisation of the oesophagus renders an infectious aetiology unlikely. Physical or chemical injury is the probable cause of the erosive oesophagitis observed in the two affected sheep. Physical injury is unlikely to have occurred naturally in multiple animals, especially considering the robust mucosa present in the sheep oesophagus. Chemical injury can be due a diverse array of substances, but most commonly strongly acidic or alkaline chemicals. Acidic damage to the oesophagus tends to be superficial as the coagulative damage elicited by the acid protects deeper mucosal layers from further insult. Alkaline materials however are capable of very deep liquefactive injury to the oesophageal mucosa, and this would be consistent with the histological changes observed in the two affected sheep22, 23.
The majority of deaths (n=22) occurred four to five days after movement into the new paddock. Sheep 1 was examined at six days post-move and the remaining three sheep were examined ten days after the move. Several sheep had died between these examination dates. No sheep died after the tenth day following the move to the new paddock. The histological changes in the oesophagus of Sheep 1 were subacute, while those of Sheep 4 had progressed further and likely represented a later stage of development of the same injury. This timeline of deaths and stage of pathology suggests a single period of oesophageal insult followed by the development of oesophagitis and progression of dehydration to death.
Affected animals came from several different weaning paddocks and so any aetiological agent responsible for the lesions were most likely present during common mustering along a public road or in the paddock to which the animals were transferred. If the latter were the case, the agent would have been only present initially in the affected paddock as new cases ceased prior to the animals' eventual transfer out of this paddock.
All three dams in the stubble paddock were fresh water (conductivity <300µS/cm). Initial testing of water pH found one dam (“G3”) to have a relatively high pH of 9.8. This, however, would not have been alkaline enough to cause the oesophageal injury seen in the affected sheep and is only marginally above European Community drinking water allowances (pH of 9.5)24. This dam was subsequently fenced off, and the possibility of contamination of the water with an injurious alkaline substance was considered but not able to be confirmed. The first common mustering point for the flock, immediately prior to entry to the affected paddock, was a public road. No obvious suspect material was found along this road, however a significant possibility remains of dumped liquid chemicals at this site. This highlights the potential risk to livestock and difficulty of determining the presence of or tracing the origin of illegally dumped chemical waste in rural environments.
Acknowledgements
Michelle Ayton, Lori Blechynden, Kristie Hann, Cate Hardy, Maree Scali and Naomi Tidd processed all diagnostic samples and provided high quality histological sections for this case.
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