JPC SYSTEMIC PATHOLOGY

CARDIOVASCULAR SYSTEM

March 2025

C-P03

 

SIGNALMENT (JPC #1844710): A breed unspecified dog

 

HISTORY: None

 

MICROSCOPIC DESCRIPTION: Lung: Focally, a large 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, a moderate amount of fibrous connective tissue, and fewer smooth muscle cells that forms frond-like proliferations into the arterial 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 outer 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 that are up to 1 mm in diameter with a thin, up to 15 µm eosinophilic cuticle with internal lateral cuticular ridges, prominent lateral chords, tall coelomyarian-polymyarian musculature, a small intestine lined by few multinucleate epithelial cells, and paired uteri or a single gonad. Multifocally, lumina of smaller pulmonary arteries and arterioles are narrowed or partially occluded by a fibroblastic myoinitimal proliferation similar to the previously described pulmonary artery, and are surrounded by numerous macrophages, eosinophils, lymphocytes, and plasma cells. Diffusely, alveolar septa are moderately thickened by an increased number of macrophages, fewer plasma cells, lymphocytes, and eosinophils. Multifocally within peribronchiolar, bronchial, and alveolar septa the smooth muscle is thickened (hypertrophy). Within the bronchial and bronchiolar lumina and peribronchilar connective tissue, there are numerous eosinophils, neutrophils, lymphocytes, fibrin, edema, and hemorrhage. 

 

MORPHOLOGIC DIAGNOSIS:

1. Lung, pulmonary artery: Endarteritis, proliferative and villous, chronic, focally extensive, moderate, with intraluminal male and female adult filarid nematodes, breed unspecified, canine.
2. Lung: Pneumonia, interstitial, eosinophilic, histiocytic, and lymphoplasmacytic, chronic, multifocal, moderate, with smooth muscle hyperplasia.

 

ETIOLOGY: Dirofilaria immitis

 

ETIOLOGIC DIAGNOSIS: Pulmonary dirofilariasis

 

GENERAL DISCUSSION: (see also P-P02)

• Heartworm disease occurs worldwide; the dog is the mammal commonly infected by Dirofilaria immitis, and 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 and right heart; rarely found in other sites such as eye and brain
• Filarid nematode in the Order Spriuridae; “American heartworm”

 

PATHOGENESIS:

• Heartworm disease is primarily a pulmonary vascular disease
• The number of circulating microfilariae is not indicative of the severity of disease
• The bacterial endosymbiont Wolbachia sp. 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 with decreased venous return, 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 > Ab-Ag deposition in glomeruli > membranoproliferative glomerulonephritis
• Association with eosinophilic pulmonary granulomatosis (EPG) has been reported with Dirofilaria immitis infections (Uzal, J Vet Diagn Invest 2020)

 

LIFE CYCLE:

 

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)

 

CLINICAL PATHOLOGY:

• Vascular parasites such as D. immitis are a cause of peripheral basophilia
• Cytology (BAL): Large numbers of eosinophils admixed with macrophages, neutrophils, plasma cells, and basophils
• Microfilaria can be found in urine sediment

 

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), male worms are smaller, between 12-20 cm in length
• Caudal lobar pulmonary arteries most severely affected
• Hepatic chronic passive congestion
• Ascites
• Fibromuscular intimal proliferations in larger vessels produce a grossly visible shaggy or roughened appearance that is pathognomonic of heartworm disease

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Pulmonary: Most commonly noted pulmonary parenchymal lesions are arterial thrombosis and periarterial granulomatous and eosinophilic inflammation and fibrosis
• 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 lateral internal cuticular ridges, thick, well-developed coelomyarian-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 due to glomerular deposition of immune complexes
• 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 highlight the internal elastic lamina to determine the degree of myointimal proliferation

 

DIFFERENTIAL DIAGNOSIS:

• Angiostrongylus vasorum (P-P02) 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 D. 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 

 

 

COMPARATIVE PATHOLOGY:

D. immitis in other species:

• 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

 

REFERENCES:

1. Boes KM. Chapter 5: Respiratory System. In: Raskin RE, Meyer DJ, & Boes KM eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2022:212.
2. 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.
3. 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.
4. Colegrove KM, Burek-Huntington KA, Roe W, Siebert U. Pinnipediae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:585.
5. Gal A, Castillo-Alcala F. Cardiovascular system and lymphatic vessels. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022: 518, 696-697.
6. Gardiner CH, Poynton SL. An Atlas of Metazoan Parasites in Animal Tissues. Washington, DC: Armed Forces Institute of Pathology; 1999:5-6; 35-39.
7. Hokamp JA, Meyer DJ. Chapter 12: Urine. In: Raskin RE, Meyer DJ, & Boes KM eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2022:436. 
8. Keel MK, Terio KA, McAloose D. Canidae, Ursidae, and Ailuridae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:247-248.
9. 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.
10. Stockham SL, Scott MA. Fundamentals of Veterinary Clinical Pathology. 2nd ed. Hoboken, NJ: Wiley; 2013: 89.
11. Uzal FA, Navarro MA, Hostetter JM, Abbott DE, Allen AL. Canine eosinophilic granulomatosis: case report and literature review. J Vet Diagn Invest. 2020; 32(2):329-335.
12. Wamsley HL. Examination of the Urine Sediment. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2014:397. 

 

 

 

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