Mechanism of Disease

The severity of disease is determined by the number of worms, duration of infection, and immune response to the infection.

Mechanism of Disease Production:

1. Physical presence of adult worms in the pulmonary artery.
   
   The adult worms denude the endothelium of the small arteries. Platelets and WBC adhere to these areas and release platelet derived growth factor. Thrombosis and proliferation of the interna and medial smooth muscle cause arterial obstruction and increased vascular permeability with leakage of plasma into the interstitium and alveoli. The pulmonary arteries dilate, become tortuous, and lose their normal tapering and arborizing pattern. With pulmonary artery obstruction, pulmonary hypertension and cor pulmonale develop (right ventricular concentric hypertrophy).
2. Obstruction of the right atrium and vena cava.
   
   An enormous worm burden develops acutely with massive numbers present in the right atrium and caudal vena cava. Intravascular hemolysis due to mechanical shearing results in anemia, hemoglobinemia, hemoglobinuria and jaundice. Signs of right heart failure occur secondary to obstruction and dysfunction of the tricuspid valve. Disseminated intravascular coagulation frequently develops. This complication occurs in endemic areas.
3. Immune mediated microfilarial destruction.
   
   In some individuals, a high antibody level results in the destruction of microfilaria within the pulmonary capillaries as they are released from the adult, resulting in one form of occult heartworm disease. These cases usually are associated with the greatest degree of pulmonary pathology and most severe clinical signs. A hypersensitivity reaction with so-called allergic pneumonitis may result due to a marked increase in capillary permeability with mixed alveolar and interstitial disease. So-called pulmonary granulomatosis may occur. This is suggested by the radiographic finding of lung lobe consolidation.
4. Dying adult worms with adulticide therapy.
   
   Adulticide therapy inevitably will cause destruction, fragmentation of adult worms, and pulmonary embolization. This will cause an acceleration of the vascular processes that create pulmonary disease. The massive bombardment of worm fragments results in:
   • Pulmonary arterial thrombosis.
   • Enhanced vascular permeability with interstitial and alveolar edema.
   • Disseminated intravascular coagulation.
   • Worsening of pulmonary hypertension.
5. Renal disease.
   
   Glomerulonephritis appears to be a common histologic lesion in heartworm disease. However, azotemia, proteinuria, and hypoalbuminemia are rare. Amyloidosis is a very rare complication with heartworm disease