JPC SYSTEMIC PATHOLOGY
Signalment: 4-year-old woolly monkey, gender unspecified
HISTOPATHOLOGIC DESCRIPTION: Kidney: Approximately 70% of arteries and arterioles are tortuous and frequently the intima are circumferentially and moderately thickened by the deposition of eosinophilic, fibrillar material (collagen, elastic fibers), which narrows and occasionally occludes vessel lumina. The tunica media of these vessels is moderately thickened by concentric layers of loosely arranged leiomyocytes (smooth muscle hyperplasia and "onion skinning"). Leiomyocytes occasionally have vacuolated sarcoplasm and hyperchromatic nuclei (degeneration). Frequently, the tunica adventitia of these vessels is mildly expanded by fibrosis. Multifocally, infiltrating the cortical interstitium and often linearly tracking vessels, there are numerous lymphocytes and plasma cells mixed with loosely arranged fibrous connective tissue (fibrosis), minimal hemorrhage and few hemosiderin-laden macrophages, which surround, separate and replace tubules and glomeruli. Among the remaining tubules, there is often tubular atrophy and loss, or tubules are ectatic and lined by attenuated epithelium. Tubules occasionally contain eosinophilic, homogenous, flocculent or granular material (granular casts and tubular proteinosis). Multifocally, Bowman’s capsule is mildly thickened by fibrous connective tissue and occasionally there is segmental or global glomerulosclerosis and atrophy of glomerular tufts. Within the medulla, there is marked interstitial fibrosis with similar tubular changes. Multifocally, the overlying capsule is undulant with multifocal indentations in areas with subjacent inflammation, and fibrosis.
- Kidney, arteries and arterioles: Arteriosclerosis, hyperplastic, circumferential, multifocal, moderate, woolly monkey, (Lagothrix lagothrica), primate.
- Kidney: Nephritis, tubulointerstitial, lymphoplasmacytic, chronic, diffuse, moderate with fibrosis, glomerulosclerosis and tubular proteinosis.
ETIOLOGIC DIAGNOSIS: Idiopathic hypertensive renal arteriosclerosis
CAUSE: Essential (Idiopathic) hypertension
- Spontaneous hypertension has been reported in rhesus macaques (Macaca mulatta) and woolly monkeys (Lagothrix sp.)
- Hypertension is classified as either primary idiopathic (essential) or secondary
- Insulin-dependent diabetes mellitus can produce glomerulosclersis, macrovascular and microvascular disease, and atherosclerosis in nonhuman primates
- Hypertension in wooly monkeys:
- Primarily affects the kidney and causes arteriolar nephrosclerosis, which occurs in 65% or more of wooly monkeys with hypertensive related disease
- Has only been reported in animals 4 years of age or older
- Is termed essential or idiopathic because it is not associated with elevated levels of plasma renin, electrolyte imbalances or hypercholesterolemia
- Arteriolosclerosis: A pattern of arteriosclerosis (thickening and loss of elasticity of arterial walls) that affects small arteries and arterioles and has a hyperplastic and a hyaline form; both forms are associated with thickening of vessel walls and luminal narrowing that may cause downstream ischemic injury
- The kidney is the primary organ affected and arteriolar nephrosclerosis occurs in more than 75% of affected animals.
- Pathogenesis of hypertensive renal arteriolosclerosis is not completely understood, and the specific cause of the initial vascular damage is unknown
- Hyperplastic form: Endothelial injury of small arteries and arterioles > platelet deposition > release of platelet-derived growth factor (PDGF) and mitogenic factors from plasma and other cells > intimal smooth muscle hyperplasia > stenosis of vessel lumina > renal ischemia > activation of renin-angiotensin system
- Hyaline form (results from a combination of):
- Deposition of plasma proteins in arteriolar vessel walls in response to endothelial injury and increased vascular permeability
- Increased deposition of basement membrane matrix
- Two overlapping mechanisms for hypertension are postulated:
- Increased blood volume: One cause is renal retention of excess sodium. Genetic factors initiate the retention of Na as the primary cause of hypertension; decreased Na excretion leads to increased blood volume, increased cardiac output, and peripheral vasoconstriction
- Increased peripheral resistance: Results from structural or functional changes in vessel walls that occurs secondary to behavioral factors or neurogenic stimuli, such as stress, obesity, lack of exercise, high sodium intake, and prolonged exposure or increased sensitivity to vasoconstrictors (i.e., renin, catecholamines); recent evidence suggests increased angiotensin II may also be a major factor
- In larger arteries, hypertension causes degenerative changes which can lead to aortic dissection and cerebrovascular hemorrhage
- Insulin-dependent diabetes mellitus causes increased vascular permeability > increased blood volume through glomerular capillaries > increased GFR > increased basement membrane thickness > secondary mesangial cell damage, cellular proliferation, matrix deposition, and proteinuria > diabetic glomerulosclerosis, glomerular hypertrophy, interstitial fibrosis, and tubular dilation and loss
TYPICAL CLINICAL FINDINGS:
- Death from congestive heart failure, renal failure, or cerebral vascular accidents
- In wooly monkeys, renin levels are not elevated despite renal lesions
TYPICAL GROSS FINDINGS:
- Kidneys range from grossly normal to pale and shrunken with reduced cortical parenchyma and numerous capsular pits and depressions
- Heart enlargement, hydropericardium, pulmonary congestion and edema, and ascites and calcification of gastric mucosa
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Small muscular arteries are variably affected
- Lesions consist of hyaline deposits beneath the intima, which become extensive and occasionally occlude the vessel lumen
- There is hyperplasia, hypertrophy, and fibrosis of the smooth muscle of the tunica media; occasionally proliferative lesions have an onion-skin pattern characterized by concentric, laminated fibrosis and smooth muscle proliferation of the intima and media
- Less frequently, there is arteriosclerosis in the pancreas, spleen, heart, and other organs
- Renal tubular atrophy, interstitial fibrosis, and glomerular changes, including collapse of basement membranes, periglomerular fibrosis, and glomerulosclerosis
- Renal allograft rejection: similar vascular changes depending on stage, history is helpful diagnostically
- Atherosclerosis: lipid-laden macrophages present in vascular tunics
- Polyarteritis nodosa: the arteritis is necrotizing and often proliferative
- Renal disease is the most common cause of hypertension in dogs and cats
- Presenting signs in the dog and cat are blindness from retinal arterial degeneration, retinal vascular tortuosity, intraocular hemorrhage, and retinal detachment
- Hypertension in the dog is associated with chronic renal failure, pheochromocytoma, hyperadrenocorticism, hypothyroidism, and diabetes mellitus
- Feline hypertension is associated with chronic renal failure, hyperthyroidism, and chronic anemia
- Vasa vasorum arteriopathy strongly correlates with hypertension in cats
- Spontaneous hypertension also occurs in the Milan strain of Wistar rat
- Swine and nonhuman primates are frequent animal models of human arteriosclerosis and atherosclerosis
- Spontaneous hypertension also occurs in several rat strains (Wistar-Kyoto, Milan, SHR (Spontaneously Hypertensive Rat), Lyon, Dahl and GH (Genetically Hypertensive Rat) are some of the more commonly used strains)
- In humans, hypertension is the most important risk factor in coronary heart disease and cerebrovascular accidents; it also linked to congestive heart failure (hypertensive heart disease) and renal insufficiency. Ninety five percent of humans cases are idiopathic, primary (essential) hypertension
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