Acute Colic in a Dartmoor Pony PDF

Pathology in Practice In collaboration with the American College of Veterinary Pathologists Acute colic in a Dartmoor pony History pulse of 80 (RI, 24 to 48 beats/min) combined with...

Pathology in Practice In collaboration with the American College of Veterinary Pathologists Acute colic in a Dartmoor pony History pulse of 80 (RI, 24 to 48 beats/min) combined with icteric sclera and muddy brown, tacky mucous mem- A 14-year-old 200-kg Dartmoor pony gelding branes. Gastrointestinal borborygmi were auscultated was presented to the North Carolina State University in all four quadrants but notably decreased. Dark red- (NCSU) Veterinary Hospital because of a 2-day his- brown urine was collected, and urine specific gravity tory of being down with acute colic. No other ponies was 1.035 (RI, 1.020 to 1.050) with the presence of on the premise were reportedly ill. A red maple leaf white blood cells (0 to 5 cells/LPF) and fine granular tree (Acer rubrum) had fallen into the pasture 3 days casts (5 to 10 casts/LPF) on urinalysis. Additionally, prior to clinical signs with several bite marks noted the PCV had further decreased (29.8%), with marked on the bark. hemolysis, and occasional eccentrocytes on the blood smear. A serum biochemistry panel was per- Clinical and Gross Findings formed and revealed increasing hyperlactatemia (> 15 mmol/L), mildly increased creatinine (2.6 mg/dL On the initial physical examination, the refer- [RI, 0.2 to 2.2mg/dL]), hyperbilirubinemia (7.3 mg/ ring veterinarian reported markedly icteric mucous dL [RI, 0.5 to 2.3]), hyperglycemia (191 mg/dL [RI, membranes with an elevated rectal temperature 65 to 110 mg/dL]), elevated AST (670 IU/L [RI, 202 of 39.6 °C (reference interval [RI], 37.2 °C to 38.6 to 338 IU/L]), and elevated CK (1,191 IU/L [RI, 120 °C) performed on October 14, 2020. The serum to 470 IU/L]). The patient was placed on intravenous biochemistry profile following the initial 48 hours fluids containing supplemental electrolytes (ascorbic of veterinary attention is summarized (Table 1). A acid) and flunixin meglumine (1.1 mg/kg, IV). CBC and serum biochemistry profile showed a PCV On October 16, 2020, the PCV further decreased of 36% (RI, 30% to 50%) with the presence of Heinz to 20% (moderate anemia) but did not decrease fur- bodies noted, marked hyperlactatemia > 12 mmol/L ther. In contrast, the lactate drastically improved to 3.3 (RI, < 2 mmol/L), and hyperbilirubinemia (no value mmol/L. Simultaneously, the initial clinical signs were reported). No urine was produced for collection at getting less severe. The pony started eating hay and this time. The primary veterinarian did not instigate passing appropriately formed feces was observed. treatment prior to referral. However, during the night, the horse began to decline The patient continued to decline overnight and once more, developed pipe stream diarrhea, and be- was referred to NCSU Veterinary Hospital on October came increasingly dull. The lactate increased to 12 15, 2020, for further workup. On presentation, the mmol/L and the patient was anuric. Multiple doses of gelding had a rectal temperature of 38.4 °C, respira- furosemide (1 mg/kg, IV) were administered with no tory rate of 16 rbpm (RI, 8 to 16 breaths/min), and urine produced. Blood gas analysis revealed a marked hyperkalemia (7.7 mmol/L [RI, 2.5 to 5.2 mmol/L]), elevated lactate (> 15 mmol/L), and marked hypo- Peter N. McGinn, DVM, MS1; Daniel Felipe Barrantes Murillo, glycemia (17 mg/dL), elevated AST (541 IU/L) and DVM, MS2; Tatiane Terumi Negrão Watanabe, DVM, MS, PhD, DACVP1,3* CK (1,779 IU/L). Serum biochemistry values, anuria despite furosemide administration, and hyperkalemia 1Department of Population Health and Pathobiology, College of suggested anuric renal failure. A urinary catheter was Veterinary Medicine, North Carolina State University, Raleigh, NC 2Department of Pathobiology, College of Veterinary Medicine, placed under sedation. Only a small amount of dark Auburn University, AL red urine was obtained. Following sedation, the horse 3Antech Diagnostics, Los Angeles, CA went down and remained in lateral recumbency. Flu- ids with dextrose and calcium were administered to *Corresponding author: Dr. Negrão Watanabe (tatiane. [email protected]) lower the potassium and protect the heart from se- vere electrolyte derangement, but the patient began Received February 28, 2023 to have seizures and died naturally. Accepted March 27, 2023 Postmortem examination revealed a diffuse doi.org/10.2460/javma.23.02.0122 brown discoloration in all the internal organs and 1222 JAVMA | AUGUST 2023 | VOL 261 | NO. 8 Unauthenticated | Downloaded 09/25/24 05:42 AM UTC Table 1—Serum biochemistry profile of a 14-year-old Dartmoor pony with acute colic after presentation to primary veterinarian and 2-day hospitalization from October 14, 2020, to October 16, 2020. Referral DVM NCSU VH Variable 10/14/20 10/15/20 10/16/20 Reference ranges Units PCV 36 29.8 20 30–50 % Lactate > 12 > 15 > 15 < 2.0 mmol/L Bilirubin Moderate (no value given) 7.3 5.7 0.5–2.3 mg/dL Glucose – 191 17 65–110 mg/dL BUN 2.2 25 38 7–25 mg/dL AST – 670 541 202–338 IU/L CK – 1191 1779 120–470 IU/L K – 3.6 7.7 2.5–5.2 mmol/L AST = Aspartate aminotransferase. BUN = Blood urea nitrogen. CK = Creatinine kinase. K = Potassium. NCSU VH = North Carolina State University Veterinary Hospital. splenomegaly (Figure 1). The kidneys were swollen with diffuse hemoglobinuric nephrosis, with a red to brown discoloration of the renal cortex and medulla. The cortex has multifocal dark red radial streaks that extend into the capsular surface. The medulla is dif- fusely red, with irregular dark red patchy areas and yellow discoloration of renal pelvis adipose tissue. Figure 1—Necropsy images of the thoracic and ab- dominal organs (A) and cut sections of the kidneys Figure 2—Photomicrographs of renal tissue sections (B) of a 14-year-old 200-kg Dartmoor pony gelding from the gelding described in Figure 1. A—The renal evaluated for a 2-day history of being down with acute tubules within the cortex and medulla contain bright- colic. A—Diffuse brown discoloration was evident in all ly eosinophilic to red, hyaline to granular material the internal organs. B—The kidneys were swollen with (hemoglobin and hyaline casts), occasionally mixed diffuse red-to-brown discoloration. The renal cortices with sloughed epithelial cells and necrotic cellular had multifocal dark red radial streaks; the medullae are debris (granular cast). H&E stain; bar = 100 µm. B— diffusely red, with irregular dark red patchy areas; and Tubules often exhibit mild ectasia with attenuated the adipose tissue in each renal pelvis has yellow dis- epithelium, sloughed epithelial cells with karyorrhec- coloration. C = Colon. J = Jejunum. L = Lung. Li = Liver. tic and pyknotic nuclei, hypereosinophilic cytoplasm K = Kidney. (necrosis), and fragmentation of tubular basement membranes (tubulorrhexis; arrowhead). H&E stain; bar = 25 µm. C—Scattered renal tubules have intra- Formulate differential diagnoses, then continue luminal mineralization (arrowheads). H&E stain; bar = reading. 100 µm. D—Highlighted orange to orange-red tubular casts confirm the presence of hemoglobin. Okajima stain; bar = 50 µm. Histopathologic findings Microscopically the lumen of renal tubules in presence of hemoglobin. The hepatic parenchyma the cortex and medulla had a brightly eosinophilic had portal tracts with mildly expanded mature fibro- to red, hyaline to granular material (hemoglobin sis and often infiltrated by scattered lymphocytes. and hyaline casts) occasionally mixed with sloughed The centrilobular to midzonal hepatocytes had an epithelial cells and necrotic cellular debris (granular expanded swollen cytoplasm, containing microve- cast; Figure 2). Tubules often exhibited one or more sicular lipid vacuoles. of the following changes: mild ectasia with attenuat- ed epithelium; epithelial cell swelling with cytoplas- Morphologic Diagnosis mic vacuolization (degeneration); karyorrhectic and pyknotic nuclei with hypereosinophilic cytoplasm and Case Summary (necrosis); fragmentation of tubular basement mem- Morphologic diagnoses: 1) severe diffuse sub- branes (tubulorrhexis); intratubular mineralization; acute tubular degeneration and necrosis with hemo- tubular epithelial cells with intracytoplasmic, globu- globin, hyaline, and granular casts; 2) mild diffuse lar, hypereosinophilic material (protein). Okajima chronic portal fibrosis and mild multifocal centrilobu- stain highlighted tubular casts orange confirming the lar microvesicular lipidic hepatocellular vacuolization. JAVMA | AUGUST 2023 | VOL 261 | NO. 8 1223 Unauthenticated | Downloaded 09/25/24 05:42 AM UTC  Case summary: Acer rubrum (Red Maple) toxic- Gross lesions associated with red maple toxicity ity in a Dartmoor pony. include renal edema and pigment nephrosis, brown discoloration of other tissues and blood, splenomeg- Comments aly, icterus, and serosal petechiation.1–4 Microscopi- cally, red maple toxicity is most often characterized Red maple leaf toxicity is primarily seen in by tubular dilation and necrosis with hemoglobin equine species but has been also reported in ducks, casts.3–5 Staining with Okajima stain will differenti- zebras, donkeys, and alpacas.1,2 Affected animals ate hemoglobin from methemoglobin. The liver and will develop acute, severe hemolysis with hemo- spleen will often exhibit centrilobular hepatocellular globinemia and/or methemoglobinemia within 18 necrosis (due to hypoxia) and erythrophagocytosis to 48 hours post-consumption of the fallen leaves, (due to hemolysis), respectively.1 as seen in this particular case.1–3 Toxicity is typical- Differential diagnoses should include leptospi- ly seen in the fall or early spring when the melting rosis, babesiosis, exertional rhabdomyolysis, end- snow uncovers previously fallen leaves.1–3 There is a stage liver disease, equine infectious anemia, and correlation between the amount of leaf decay and nitrate toxicity.3,4 Diagnosis relies on clinical testing the toxic potency of the leaves to horses.2 Typically, for hemolysis and methemoglobinemia, a good clini- the disease only develops with the consumption of cal history, and ruling out the other etiologies with partially decayed to completely dead leaves, which laboratory testing.1–4 may remain toxic for weeks.2 It is estimated that con- Treatment of red maple toxicity is rarely reward- sumption of 0.5% to 0.8% of body weight or 1.5 to 3.0 ing due to the rapid clinical course and the uniden- g/kg of body weight of partially decayed dry leaves tified toxin. Therapies are aimed at palliative care is enough to cause intoxication with a fatality rate and addressing sequelae to severe hemolysis. Blood greater than 60%.1,2 transfusions and colloidal fluids are the hallmark of The exact toxin in red maple leaves is not defini- treatment but may lose efficacy in the face of devas- tively identified, although it is hypothesized to be tating oxidative hemolysis.1–3 Fluid therapy, activat- a nitrogenous compound, gallic acid, or polypheni- ed charcoal (if timely), mineral oil to inhibit further col.1,2 It is believed that the dead leaves generate absorption of the toxin, and as a gastroprotectant, potent oxidants which overcome the glutathione- non-steroidal, and corticosteroids have all been de- reducing system in red blood cells resulting in the scribed with varying outcomes.1–3 While administra- formation of Heinz bodies.2,3 Heinz bodies weaken tion of methylene blue is considered non-efficacious the integrity of the red blood cell membrane allow- in horses and may even worsen the condition, ascor- ing for osmotic lysis and the release of hemoglobin bic acid (vitamin C) has recently shown promise in (hemoglobinemia). Hemoglobinuria develops once reducing methemoglobin.1–3 the renal reabsorption threshold for hemoglobin is surpassed.4 The proximal tubule and the medulla of the kidney are highly metabolic and thus exquisitely Acknowledgments sensitive to decreased oxygenation.4 In addition to No external funding was used in this case. The authors anemia, oxygen delivery is further exacerbated by declare that there were no conflicts of interest. the oxidation of free hemoglobin to form methe- The authors would like to acknowledge the initial contri- butions of Dr. Jonathan Nagel, VMD, DACVP, and the NCSU moglobin.3 Reduced oxygen-carrying capacity de- histology laboratory for their technical support. prives the horse of oxygen and results in shock and renal nephrosis. Pooled hemoglobin casts within the tubules may block the tubules and lead to par- References tial or complete obstruction.4 A cycle is created as 1. Burrows G, Tyrl R. Chapter sixty-seven: Sapindaceae Juss. obstruction creates further tubular necrosis and de- In: Burrows GE, Tyrl RJ, eds. Toxic Plants of North Ameri- generation which leads to decreased resorption and ca. 2nd ed. Wiley-Blackwell; 2013:1110–1124. increased pooling of hemoglobin.3 2. Alward A, Corriher CA, Barton MH, Sellon DC, Blikslager Clinical signs associated with red maple toxic- AT, Jones SL. Red maple (Acer rubrum) leaf toxicosis in ity include depression, lethargy, anorexia, colic, dark horses: a retrospective study of 32 cases. J Vet Intern Med. 2006;20(5):1197–1201. brown or red urine (hemoglobinuria or methemoglo- 3. Witonsky SG, Grubbs ST, Andrews FM. A case of red ma- binuria), muddy brown or cyanotic membranes, ane- ple (Acer rubrum) toxicity associated with fallen branch- mia, icterus, and Heinz bodies on cytology.1–3 The es. Equine Vet Educ. 2001;13(3):119–123. disease most commonly manifests as a hemolytic 4. Cianciolo RE, Mohr FC. Chapter 4: Urinary system. In: crisis with hemoglobinuria or methemoglobinuria, Grant Maxie M, ed. Jubb, Kennedy & Palmer’s Pathol- but both can occur leading to a poorer prognosis.1–3 ogy of Domestic Animals. Vol 2. 6th ed. WB Saunders; 2016:376–464. The disease progresses quickly, and the onset of clin- 5. Agrawal K, Ebel JG, Altier C, Bischoff K. Identifica- ical signs may occur within 18 hours of ingestion.1 If tion of protoxins and a microbial basis for red maple the disease progresses past 48 hours, laminitis may (Acer rubrum) toxicosis in equines. J Vet Diagn Invest. occur due to systemic hypoxia.1–3 2013;25(1):112–119. 1224 JAVMA | AUGUST 2023 | VOL 261 | NO. 8 Unauthenticated | Downloaded 09/25/24 05:42 AM UTC