JPC SYSTEMIC PATHOLOGY
SIGNALMENT (JPC #1844710): A breed unspecified dog
MICROSCOPIC DESCRIPTION: Lung: Focally, a pulmonary artery is moderately dilated and tortuous. The internal elastic lamina is segmentally effaced and the tunica intima is thickened up to 20x by plump, reactive fibroblasts and a moderate amount of fibrous connective tissue and fewer smooth muscle cells that forms frond-like proliferations into the lumen, which are often lined by hypertrophied (reactive) endothelial cells (proliferative arteritis) and infiltrated by few lymphocytes, plasma cells, eosinophils and neutrophils. Peripherally, in the tunica intima, there are few small blood vessels lined by reactive endothelial cells arranged perpendicularly to the fibroblasts and connective tissue (granulation tissue). Within the arterial lumen, there are multiple cross sections of adult male and female filarid nematodes up to 1 mm in diameter with a thin eosinophilic cuticle, prominent lateral chords that have an internal lateral cuticular ridge, tall coelomyarian and polymyarian musculature, a small intestine lined by few multinucleate epithelial cells and paired uteri or a single gonad. Multifocally, arteriole lumina are narrowed or partially occluded by a fibroblastic myoinitimal proliferation similar to the pulmonary artery, and are surrounded by numerous macrophages, eosinophils, lymphocytes and plasma cells. Diffusely, alveolar septa are moderately thickened by an increased number of alveolar macrophages, fewer plasma cells, lymphocytes and eosinophils. Within the bronchial and bronchiolar lumina and peribronchilar connective tissue, there are numerous eosinophils, neutrophils, lymphocytes, fibrin, edema and hemorrhage.
- Lung, artery: Endarteritis, proliferative and villous, chronic, focally extensive, moderate, with intra-arterial male and female filarid nematodes, etiology consistent with Dirofilaria immitis, breed unspecified, canine.
- Lung: Pneumonia, eosinophilic, histiocytic, and lymphoplasmacytic, multifocal, moderate, with multiple granulomas.
ETIOLOGY: Dirofilaria immitis
ETIOLOGIC DIAGNOSIS: Pulmonary dirofilariasis
- Heartworm disease occurs worldwide, with the dog being the only significant reservoir host; in areas of enzootic infection in dogs, other mammals may also be infected including, rarely, humans
- Adult worms live in pulmonary arteries an right heart; rarely found in other sites such as eye and brain
- Filarid nematode in the Order Spriuridae; “American heartworm”
- Heartworm disease is primarily a pulmonary vascular disease
- The number of circulating microfilariae is not indicative of the severity of disease
- The bacterium Wolbachia harbored by D. immitis is essential for the normal development of the parasite and contributes to disease pathogenesis
- Mechanical irritation of the intima by adult filarids and microfilaria > myointimal proliferation (irritation, endothelial damage, platelet derived growth factor (PDGF)-mediated) and sclerosis > proliferative endarteritis > pulmonary hypertension and interstitial fibrosis > congestive right heart failure
- Vena caval syndrome: Large number of adult worms in the right atrium and vena cava > venous obstruction and decreased venous return and tricuspid valve regurgitation and pulmonary hypertension > decreased left ventricular preload > decreased circulation > shock
- Renal: Adult and microfilaria induce Th2-mediated immune response > Ab-Ag immune complex formation > deposition in glomeruli > membranoproliferative glomerulonephritis
- L1, L2, and early L3 larvae are obligate parasites of Aedes , Culex spp., and Anopheles spp. > larvae enter definitive host when the mosquito feeds > larvae mature and reach the right ventricle in 3-4 months > adults reside in pulmonary vasculature and release microfilaria into the bloodstream
TYPICAL CLINICAL FINDINGS:
- Asymptomatic to severe systemic disease including vena caval syndrome
- Cough and exercise intolerance
- Vena caval syndrome (young dogs with large burden): Weakness, anorexia, bilirubinuria, hemoglobinuria and anemia (due to right atrial turbulence and shear-induced mechanical hemolysis; microangiopathic anemia with schistocytes)
TYPICAL GROSS FINDINGS:
- Adult heartworms in pulmonary arteries and right ventricle; less frequently in the left ventricle and vena cava in heavy infestations (> 50 worms)
- Caudal lobar pulmonary arteries most severely affected
- Hepatic chronic passive congestion
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Pulmonary: Most commonly noted pulmonary parenchymal lesions are arterial thrombosis and periarterial granulomatous inflammation
- Fibromuscular tunica intima proliferation is characteristic; may be nodular, irregular or villous with enmeshed worms and leukocytes
- Cardiovascular: Endarteritis with infiltration of eosinophils and neutrophils
- Adult parasites are found in pulmonary artery and right heart and are characterized by evenly-spaced lateral internal cuticular ridges, thick, well-developed coelomyarian and polymyarian musculature and a small (proportional to body size) intestine
- Microfilaria: Present in gravid females; appear to lack musculature and resemble a cuticular-limited “bag of nuclei”
- Renal: Membranoproliferative glomerulonephritis
- Aberrant migration of larva can cause granulomas, with or without association of larvae and eggs in multiple organs including the brain, kidney, tracheobronchial lymph nodes, adrenal gland, skin, liver, pancreas, pericardial sac, urinary bladder, femoral artery, intestinal tract, thyroid gland, pituitary gland, skeletal muscle, heart and eye
ADDITIONAL DIAGNOSTIC TESTS:
- Antigen SNAP test
- Modified Knott’s test
- Microfilarial testing: Blood smear with microfilaria: 290-315 µm long, straight body and tail with tapered head
- Radiographs: Radiographic abnormalities develop early in heartworm disease and are useful in determining the severity of changes to pulmonary parenchemya; changes include right ventricular enlargement; increased prominence of the main pulmonary segment; increased size and density of the pulmonary arteries and pulmonary artery tortuosity and “pruning”
Special histochemical stains such as Movat or Verhoeff-van Gieson will aid in identifying the internal elastic lamina and determining the degree of myointimal proliferation
- Angiostrongylus vasorum is a metastrongylid nematode (superfamily Metastrongyloidae, family Angiostrongyloidae)
- Most pathogenic lungworm of dogs; “French heartworm” because it was first reported in France in the 1800s; causes right heart failure and extensive pulmonary lesions as a consequence of egg embolization and pulmonary arterial thrombosis
- Gross lesion: Small, 1-2 mm diameter, red, firm, multinodular to confluent areas of hemorrhage and edema at the lung periphery; chronic heart failure; adult worms with a “barber pole” appearance; smaller than immitis, have a large intestine compared to body size
- Microscopic findings: Pyogranulomatous interstitial pneumonia; proliferative endarteritis, thrombosis, thickening of tunica intima by fibromuscular tissue, medial hypertrophy, infiltration of eosinophils, lymphocytes and plasma cells; chronic cases may have fibrosis and vascular recanalization of arterial thrombi
- Dipetalonema reconditum is nonpathogenic cutaneous parasite that produces microfilaria: 270-290 µm, curved body, blunt head, and button-hook tail
- All canids are susceptible and can serve as reservoir hosts
- Domestic felids, ferrets, California sea lions, and other species are aberrant (dead-end) hosts; no transmission occurs because of absence of microfilaremia
- Cats: Usually infected with low numbers of adults (often one) and frequently male-only infections; develop similar proliferative and villous endarteritis, often with marked eosinophilia; can be asymptomatic or cause sudden death; occasionally develop heartworm-associated respiratory disease
- Bourque AC, Conboy G, Miller LM, Whitney H. Pathological findings in dogs naturally infected with Angiostrongylus vasorum in Newfoundland and Labrador, Canada. J Vet Diagn Invest. 2008;20(1):11-20.
- Caswell JL, Williams KJ. Respiratory system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier; 2016:492, 513.
- Gardiner CH, Poynton SL. An Atlas of Metazoan Parasites in Animal Tissues. Washington, DC: Armed Forces Institute of Pathology; 1999:5-6; 35-39.
- Miller LM, Gal A. Cardiovascular system and lymphatic vessels. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:568-569, 615-616.
- Robinson WF, Robinson NA. Cardiovascular system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. St. Louis, MO: Elsevier; 2016:83-85.