Write the etiology, pathogenesis and clinical manifestations of Equine myoglobinuria.

Etiology (Causes)

The etiology of equine myoglobinuria is multifactorial and can be broadly categorized into exertional and non-exertional causes:

• Exertional Causes: These are the most common.
• Intense Exercise: Particularly in horses unaccustomed to strenuous work, such as racing, endurance events, or hill work.
• Heat and Humidity: Increased body temperature and dehydration exacerbate muscle damage.
• Poor Conditioning: Lack of adequate muscle conditioning increases susceptibility.
• Improper Footing: Slippery or uneven surfaces can cause muscle strain.
• Non-Exertional Causes: These are less common but often more serious.
• Malignant Hyperthermia (MH): A genetic disorder triggered by anesthesia or stress, leading to rapid muscle breakdown.
• Neuromuscular Diseases: Conditions like polysaccharide storage myopathy (PSSM) and atypical PSSM (PSSM2) cause muscle dysfunction and damage.
• Trauma: Crush injuries, severe bruising, or compartment syndrome can release myoglobin.
• Toxins: Certain plants (e.g., locoweed), drugs (e.g., statins), and mycotoxins can induce muscle damage.
• Electrolyte Imbalances: Hypokalemia (low potassium) is a known trigger.
• Genetic Predisposition: Some breeds, like Thoroughbreds and Quarter Horses, are considered more predisposed.

Pathogenesis (Disease Mechanism)

The pathogenesis of EM involves a cascade of events:

1. Muscle Damage: The initiating event is damage to muscle fibers. This can be due to direct trauma, metabolic stress, genetic factors, or toxic exposure.
2. Myoglobin Release: Damaged muscle cells release myoglobin into the sarcoplasm (intracellular fluid).
3. Entry into Circulation: Myoglobin diffuses into the bloodstream. Its molecular weight (approximately 800 Da) allows it to pass through the glomerulus in the kidney, particularly when the glomerular filtration rate is high (e.g., during exercise).
4. Renal Tubular Reabsorption: Normally, the kidneys reabsorb myoglobin. However, when the amount exceeds the reabsorptive capacity, it spills into the urine. Myoglobin can also directly damage the renal tubules, further impairing reabsorption.
5. Pigment Cast Formation: Myoglobin can bind to Tamm-Horsfall protein, forming pigment casts that obstruct renal tubules, contributing to acute kidney injury.

Stage	Event	Mechanism
Muscle Damage	Muscle Fiber Rupture	Exertion, Trauma, Genetic, Toxin
Myoglobin Release	Release into Sarcoplasm	Cellular Lysis
Systemic Circulation	Entry into Bloodstream	Diffusion
Renal Filtration	Glomerular Passage	High Filtration Rate
Renal Reabsorption	Overflow & Tubular Damage	Exceeding Reabsorptive Capacity

Clinical Manifestations (Signs and Symptoms)

The clinical signs of equine myoglobinuria can vary depending on the severity and underlying cause:

• Dark Urine: The hallmark sign, ranging from tea-colored to dark brown.
• Muscle Pain & Stiffness: Affected horses may exhibit reluctance to move, lameness, and muscle soreness.
• Weakness: Generalized weakness and fatigue are common.
• Depression: Apathy and decreased appetite may be observed.
• Increased Respiratory Rate: Can be due to pain or metabolic acidosis.
• Electrolyte Imbalances: Further complications can arise due to renal tubular damage and losses.
• Jaundice: In severe cases, renal failure can lead to bilirubin accumulation.
• Colic Signs: Abdominal discomfort and pain.

Diagnosis typically involves urinalysis to confirm the presence of myoglobin and blood work to assess muscle enzyme levels (creatine kinase – CK, aspartate aminotransferase – AST, alanine aminotransferase – ALT) and renal function.