JPC SYSTEMIC PATHOLOGY

URINARY SYSTEM

November 2023

U-M01

 

Signalment: 4-year-old woolly monkey, gender unspecified

HISTORY: Unknown

 HISTOPATHOLOGIC DESCRIPTION: Kidney: Approximately 70% of arteries and arterioles are prominent and tortuous, and the overlying capsule is undulant with multifocal indentations overlying areas of inflammation and fibrosis. There is moderate circumferential intimal thickening with deposition of eosinophilic, fibrillar material (collagen, elastic fibers), which narrows and occasionally occludes vessel lumina. There is moderate thickening of the tunica media of these vessels by concentric layers of smooth muscle hyperplasia ("onion skinning"). Smooth muscle cells occasionally have vacuolated sarcoplasm and hyperchromatic nuclei (degeneration). Frequently, the tunica adventitia of these vessels is mildly expanded by fibrosis. Multifocally separating and occasionally replacing tubules and glomeruli within the cortex and often tracking vessels, there are numerous lymphocytes and plasma cells mixed with loosely arranged fibrous connective tissue (fibrosis), minimal hemorrhage, and few hemosiderin-laden macrophages. Multifocally, Bowman’s capsule is mildly thickened by fibrous connective tissue and occasionally there is segmental or global glomerulosclerosis and atrophy of glomerular tufts. There is often tubular atrophy and loss, and the remaining tubules are ectatic and lined by attenuated epithelium. Tubules occasionally contain eosinophilic, homogenous, flocculent or granular material (granular casts and tubular proteinosis). Within the medulla, there is marked interstitial fibrosis with similar tubular changes. 

MORPHOLOGIC DIAGNOSES:

1. Kidney, arteries and arterioles: Arteriosclerosis, hyperplastic, circumferential, multifocal, moderate, woolly monkey, (Lagothrix lagothrica), primate.

2. Kidney: Nephritis, tubulointerstitial, lymphoplasmacytic, chronic, diffuse, moderate with fibrosis, glomerulosclerosis, and tubular atrophy and proteinosis.

 ETIOLOGIC DIAGNOSIS: Idiopathic hypertensive renal arteriosclerosis

CAUSE: Essential (Idiopathic) hypertension

GENERAL DISCUSSION: 

• Systemic hypertension may be primary (essential) or secondary
  • Primary (essential) is the most common form in humans; rare in domestic animals; prevalent in woolly monkeys, owl monkeys, and pygmy marmosets; also reported in African green monkeys and rhesus macaques; frequently associated with renal arteriosclerosis
  • Secondary is more common in domestic animals and may be due to chronic renal disease (most commonly caused by renal disease in dogs/cats, present in 60% of canine CRD cases), hyperthyroidism, pheochromocytoma, diabetes mellitus, hyperaldoteronism, etc.
• “Hypertensive renovascular disease” describes the vascular manifestations of hypertension within the kidney (and some other organs); lesions include both arteriosclerosis (hyaline and proliferative forms) and fibrinoid necrosis

PATHOGENESIS:

• Chronic kidney disease can be both a cause/exacerbating factor and a consequence of hypertension via several mechanisms including:
  • Sodium retention
  • Activation of the renin-angiotensin-aldosterone system
  • Increased sympathetic tone 
• Angiotensin II promotes renal inflammatory processes and is related hypertrophic renal vessels, podocyte effacement, albuminuria, and glomerulus extracellular matrix accumulation (Mongragon-Huerta, Vet Pathol 2022)
• Hypertension à increased hydrostatic pressure à glomerular hyperfiltration à glomerular capillary/podocyte damage à (if prolonged) glomerulosclerosis, progressive nephron loss, interstitial fibrosis
  • Loss of autoregulation of renal blood flow associated with alterations of smooth muscle of the afferent arterioles can cause hypertrophied glomeruli and segmental glomerulosclerosis (Cooley, Vet Pathol 2022)
  • Interstitial inflammatory fibrosis can cause entrapment of peritubular capillaries and renal ischemia with obsolescent glomeruli (Cooley, Vet Pathol 2022)
• Pressure-induced vascular damage primarily occurs in small arteries and arterioles; manifests as arteriosclerosis (hyaline or proliferative) and fibrinoid necrosis; these vascular lesions also perpetuate the hypertension
• Some degeneration in small arteries and arterioles is due to uremia; can affect vessels in the kidney, stomach, tongue, colon, and urinary bladder, producing ischemia and infarction
• Hypertension can lead to heart failure due to cardiac pressure overload, sympathetic overactivity, and coronary artery disease (Cooley, Vet Pathol 2022)

TYPICAL CLINICAL FINDINGS:

• High systolic blood pressure; may have high heart rate (due to high sympathetic activity)
• Dogs and cats: blindness (retinal arterial degeneration, hemorrhage, detachment)
• Congestive heart failure, renal failure, or cerebral vascular accidents 
• Death

TYPICAL GROSS FINDINGS:

• Kidneys normal to pale and shrunken with reduced cortical parenchyma and numerous capsular pits and depressions 
• Perinephric pseudocyst formation (collection of fluid between the renal capsule peritoneum)
• Ventricular hypertrophy, hydropericardium, pulmonary congestion and edema, and ascites
• Epistaxis

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Glomerulus: Collapse of basement membranes, periglomerular fibrosis, and glomerulosclerosis 
• Interstitial fibrosis and renal tubular atrophy
• Hypertensive vascular lesions: Affects small muscular arteries/arterioles; present in >95% of human hypertension cases
  • Hyaline arteriosclerosis (degeneration): amorphous, brightly eosinophilic material in vessel walls beneath the intima, may be extensive and occlude lumen 
  • Hyperplastic arteriosclerosis: Concentric, laminated fibrosis and smooth muscle proliferation of the intima and media (onion skin)
  • Less commonly affects arteries of pancreas, spleen, heart, other organs

 

DIFFERENTIAL DIAGNOSES:

• Arteriosclerosis
  • Renal allograft rejection: may have similar vascular changes, history important
  • Atherosclerosis: lipid-laden macrophages present in vascular tunics
  • Polyarteritis nodosa: necrotizing arteritis, often proliferative

COMPARATIVE PATHOLOGY: 

• Wooly monkeys: Spontaneous hypertension reported in animals > 4 years of age; primarily affects the kidney; causes arteriolar nephrosclerosis, glomerulosclerosis, tubular atrophy, interstitial fibrosis, interstitial lymphocyte infiltration; termed essential (idiopathic) because it is not associated with elevated levels of plasma renin, electrolyte imbalances or hypercholesterolemia 
• Western pygmy marmosets: Recent report of presumed systemic hypertension in a captive colony; lesions included renal arteriolar hypertrophy, hyaline and proliferative arteriosclerosis, fibrinoid necrosis, glomerulosclerosis, and nephrosclerosis (Cooley, Vet Pathol 2022)
• NWM, OWM, and great apes: May occur as part of gestation/pre-eclampsia; causes facial edema (early), proteinuria (late), encephalopathy
• Lowland gorilla: Hypertension can cause fibrosing cardiomyopathy
• Chimpanzees: Glomerulosclerosis and interstitial fibrosis (suggestive of hypertension) often occurs in association with myocardial fibrosis; link between cardiac disease and chronic renal disease referred to as “cardiorenal syndrome,” link also exists in orangutans
• Cats: Hypertensive encephalopathy characterized by arteriolar hyalinosis and arteriosclerosis with edema in subcortical white matter +/- hemorrhage; caudal herniation of the cerebrum/cerebellum (Vet Pathol 2019)
• Dogs: Hypertensive encephalopathy characterized by infarction and intracerebral hemorrhage (Vet Pathol 2019)
• Spontaneous hypertensive rats: Develop hypertension around 6 weeks of age; in prehypertensive state, demonstrated to have increased glomerular area, BM thickness, collagen fiber content, and arterial wall thickness; greater COX-2 and immature renin expression in the cortex; lower renin expression in cortex; and higher plasma AngII concentration (Mondragon-Huerta, Vet Pathol 2022)
• Other lab animals: Mild hypertension seen in guinea pigs with nephrosclerosis (CRD), rats with chronic progressive nephropathy, and hamsters with glomerulonephropathy/degenerative renal disease
• Western gray kangaroos: Captive mature and aged animals from a US zoo population had a high prevalence of lesions consistent with hypertension (unknown etiology)
• Captive red panda: Case report of systemic hypertension with parenchymal brain hemorrhage and death; featured arteriolar hyalinosis and arteriosclerosis, arterial tunica media hypertrophy/hyperplasia, and infiltration of arterial walls by lipid-laden macrophages; lymphoplasmacytic tubular nephritis, interstitial fibrosis, glomerulosclerosis; myocardial fibrosis; PCR positive for red panda amdoparvovirus (unknown significance) (Gola, J Comp Pathol 2023)

References:

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