Hemoglobinuria

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Red-brown discoloration of the urine (below) suggests hemoglobinuria, hematuria, or myoglobinuria; however, red discoloration of the plasma (right) indicates that hemoglobinemia is present and this probably produced the hemoglobinuria.
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Hemoglobinuria is a blood disorder of cats defined as a loss of hemoglobin or myoglobin through the glomeruli in an amount sufficient to cause a positive reaction to a test for blood in the urine when the patient is tested by the pseudophosphatase-orthotoluidine method.

Pathophysiology

Intravascular hemolysis causes release of free hemoglobin into the plasma. Hemoglobin forms a complex with haptoglobin. Once haptoglobin is saturated, free hemoglobin appears in the blood, divides into subunits, and is cleared from the blood by the kidneys. Some unbound plasma hemoglobin releases ferriheme, which reversibly binds to either albumin (methemalbumin) or hemopexin, a plasma protein. Free hemoglobin, hemoglobin-haptoglobin complex, hemoglobin subunits, methemalbumin, ferriheme-hemopexin complex, and bilirubin all contribute to the color of plasma. Hemoglobin complexes, when in concentrations > about 50 mg/dl of plasma, are detectable as pink plasma.

Myoglobin released from damaged muscle does not bind to serum proteins, is rapidly cleared by the liver and kidneys, and is not associated with pink plasma. Both hemoglobin and myoglobin are recovered and metabolized by the proximal renal tubule cells. Only after the renal tubular uptake mechanism is saturated will these proteins appear in the urine.

Systems Affected

Renal/Urologic - hemoglobin and myoglobin can be nephrotoxic, particularly when renal perfusion is compromised.
Hemic/ Lymph/Immune - intravascular hemolysis, extensive muscle damage, and hypoxia can precipitate disseminated intravascular coagulopathy (DIC).
Low oxygen carrying capacity (acute) can lead to secondary central lobular liver cell damage, lactic acid acidosis, and shock, which in turn exacerbates hypoxia.

Clinical signs

Neonatal isoerythrolysis (blood type A queen with type B kitten) in the British, Devon rex, Abyssinian, Birman, Himalayan, Persian, Scottish fold, and Somali breeds. Neonates die within 2 days of birth.

A wide variety of clinical signs are associated with specific causes. Signs associated with anemia such as tachycardia, easy fatigue, pale mucous membrane, fever, and icterus are not seen in patients with muscle damage or hematuria. Fever may be associated with intravascular hemolysis. DIC secondary to intravascular hemolysis or muscle trauma may induce hematuria. Patients with muscle damage have muscle tenderness or bruising.

Causes

  • Hemoglobinuria
Genetic associated
Pyruvate kinase deficiency
Phosphofructokinase deficiency
  • Toxins And Drugs
Chlorates, Benzocaine, Copper, Dimethyl sulfoxide (DMSO), Menadione (Vitamin K3), Mercury, Methylene blue, Nitrates, Methionine, Phenazopyridine, Paracetamol (acetaminophen), Phenylhydrazine, Propylene glycol, Propylthiouracil, Snake venom (Elapidae), Zinc, Plants, Onions
  • Physical Agents
Burns (severe)
Crush injury
Electric shock
Extreme exercise
Heatstroke
Hypoosomotic solution
Microangiopathy (e.g., caval syndrome and DIC)
  • Infectious Agents
Babesiosis (i.e., B. canis but usually not B. gibsoni or B. vogeli)
Feline hemobartonellosis (rarely causes intravascular hemolysis)
Leptospirosis (i.e., L. icterohemorhagica)
  • Immune-Mediated
Idiopathic immune-mediated hemolytic anemia
Incompatible blood transfusion
Neonatal isoerythrolysis - blood type A queen with type B kittens
Systemic lupus erythematosis
  • Deficiencies
Hypophosphatemia (induced by hyperalimentation or diabetes mellitus).

Treatment

Copious amounts of fluids to maintain renal function especially in the face of shock
Exercise induced hematuria has a benign, self-limiting course.
Avoid stress and excitement if the patient has anemia or copper-associated liver disease.
Avoid hyperventilation if the patient has phosphofructokinase deficiency.
Lactated Ringer's solution if the patient is dehydrated; maintenance fluids if not

References

1. Ettinger S, ed. Textbook of veterinary internal medicine: Disease of the dog and cat. 4th ed. Philadelphia: WB Saunders, 1995.

2. Jain NC, ed. Schalm's veterinary hematology. 4th ed. Philadelphia: Lea & Febiger, 1986.

3. Kaneko JJ. ed. Clinical biochemistry of domestic animals. 4th ed. San Diego: Academic Press, 1989.

4. Osborne CO, Stevens JB. Handbook of canine & feline urinalysis. Saint Louis: Ralston Purina, 1981.

5. Sherding RG, ed. The cat: diseases and clinical management. 2nd ed. New York: Churchill Livingstone, 1994.