Large Animal Internal Medicine Flashcards

A 7-year-old Quarter Horse mare presents with acute onset of profound weakness, muscle fasciculations, and dysphagia. Serum chemistry reveals markedly elevated CK and AST. EMG shows complex repetitive discharges and positive sharp waves. A muscle biopsy demonstrates vacuolar myopathy with periodic acid-Schiff (PAS)-positive inclusions. Which mutation is most likely responsible for this presentation?

Answer: GYS1 gain-of-function mutation causing glycogen synthase overactivity

The PAS-positive vacuolar inclusions represent excessive glycogen accumulation, hallmark of Polysaccharide Storage Myopathy (PSSM) Type 1, caused by a gain-of-function mutation in GYS1 (glycogen synthase 1). This leads to constitutively active glycogen synthase, causing unbranched polysaccharide accumulation. RYR1 mutations cause Malignant Hyperthermia. SCN4A mutations underlie Hyperkalemic Periodic Paralysis. TRIM63 mutations are associated with human muscular atrophy, not equine PSSM.

A 3-week-old Holstein calf presents with severe diarrhea, depression, and inability to stand. Blood gas analysis: pH 7.08, PaCO2 28 mmHg, HCO3 8 mEq/L, BE -18. The strong ion difference (SID) is calculated at 14 mEq/L (normal 40-44 mEq/L). D-lactate concentration is 8 mmol/L. Which statement BEST characterizes the acid-base disturbance?

Answer: Pure high anion gap metabolic acidosis driven primarily by D-lactic acidosis from enteric bacterial fermentation

This calf has a classic presentation of neonatal calf diarrhea with D-lactic acidosis. The markedly low SID (14 vs. normal 40-44 mEq/L) and elevated D-lactate (produced by enteric bacteria fermenting unabsorbed carbohydrates) confirm a high anion gap metabolic acidosis. The respiratory alkalosis (low PaCO2=28) is compensatory, not a co-primary disorder. Hyperchloremic acidosis would show normal anion gap and normal or elevated SID. Dilutional acidosis requires prior fluid administration, not mentioned here.

A 12-year-old Thoroughbred gelding is referred for evaluation of progressive exercise intolerance and episodic synchronous diaphragmatic flutter (SDF) following endurance competitions. Electrolytes on arrival after a bout show: Na 138, K 2.8, Cl 90, Ca (total) 7.2 mg/dL, Mg 1.0 mg/dL. Which electrolyte abnormality is the PRIMARY driver of SDF in this horse?

Answer: Hypocalcemia causing reduced threshold for phrenic nerve depolarization at the cardiac impulse

Synchronous diaphragmatic flutter ('thumps') occurs when the phrenic nerve depolarizes with each cardiac impulse. Ionized hypocalcemia is the primary driver — low ionized calcium reduces the threshold for nerve depolarization, making the phrenic nerve susceptible to the electrical field generated by the heart at the thoracic inlet. While hypomagnesemia and hypochloremic alkalosis (which reduces ionized calcium further) are contributing factors, hypocalcemia is the cardinal electrolyte abnormality responsible for SDF. Hypokalemia causes muscle weakness, not flutter.

A 6-year-old Suffolk ewe presents with progressive weight loss, submandibular edema, and pasture-mate deaths over 2 months. Fecal egg count: 12,000 EPG Haemonchus contortus. You initiate treatment with monepantel (amino-acetonitrile derivative). Three weeks later, repeat FEC shows 9,800 EPG. A fecal egg count reduction test (FECRT) confirms <50% reduction. ACR-8 gene sequencing of recovered larvae reveals a premature stop codon. What is the mechanism of resistance demonstrated?

Answer: Loss-of-function mutation in the DEG-3 subfamily acetylcholine receptor subunit ACR-8, eliminating the drug target

Monepantel acts on nematode-specific DEG-3 subfamily acetylcholine receptors, particularly the ACR-8 subunit. Resistance to monepantel is mediated by loss-of-function mutations (including premature stop codons, frameshift mutations) in acr-8, which eliminate the target receptor entirely. This is a target-site resistance mechanism distinct from the efflux-pump (pgp-9) mechanism seen with macrocyclic lactones or metabolic resistance. Latrophilin receptors are targeted by emodepside, not monepantel.

A 9-year-old Hereford bull presents with a 4-month history of bilateral nasal discharge, progressive dyspnea, and weight loss. Endoscopy reveals a cauliflower-like mass at the ethmoid region. Histopathology shows neoplastic cells with characteristic 'Feulgen-positive' intranuclear inclusions and syncytia formation. PCR confirms enzootic nasal tumor virus (ENTV-2). Which retroviral mechanism drives autonomous tumor growth in affected epithelial cells?

Answer: Insertional activation of host proto-oncogenes by the ENTV-2 provirus long terminal repeat (LTR) enhancer elements

ENTV-2 (Enzootic Nasal Tumor Virus) is a betaretrovirus that, like JSRV in pulmonary adenomatosis, lacks classical viral oncogenes. Transformation occurs through insertional mutagenesis — the proviral LTR contains potent enhancer elements that activate adjacent host proto-oncogenes (particularly Ras and PI3K pathway genes) upon integration. The viral envelope protein itself also has transforming activity via receptor tyrosine kinase signaling, but the primary driver at the population level is LTR enhancer-mediated insertional activation. ENTV does not carry transduced v-onc genes, and the US11 mechanism is herpesviral.

A 4-year-old llama presents with a 6-week history of progressive ascending hindlimb ataxia that has now involved the forelimbs. CSF analysis: protein 85 mg/dL (normal <40), WBC 3 cells/μL, xanthochromia absent. MRI of the cervicothoracic junction shows intramedullary T2 hyperintensity without gadolinium enhancement. Serum and CSF Parelaphostrongylus tenuis ELISA are negative. Thiamine levels are normal. Which diagnosis BEST fits this presentation in a South American camelid?

Answer: Camelid spinal cord disease (CSCD) due to aberrant Parelaphostrongylus odocoilei migration, seronegative due to poor antibody cross-reactivity with P. tenuis antigen

South American camelids (llamas, alpacas) are aberrant hosts for multiple Parelaphostrongylus species. P. odocoilei causes spinal cord disease in camelids with ascending myelopathy, whereas P. tenuis more commonly causes cerebrocortical signs. Critically, the standard P. tenuis ELISA has poor sensitivity for P. odocoilei infection due to limited antigenic cross-reactivity, producing false-negative serology. The CSF shows elevated protein with minimal pleocytosis (albuminocytologic dissociation), consistent with migration-associated myelopathy. Cervical compressive myelopathy would show gadolinium enhancement at the compression site. Thiamine deficiency causes cortical lesions with gadolinium-enhancing necrosis. S. neurona is rare in camelids and usually shows more pronounced pleocytosis.