Renal Vascular Anatomy and Diseases

• Renal vascular diseases include a range of conditions affecting the blood vessels of the kidneys.
• The presentation addresses normal renal vascular anatomy, nephrosclerosis (benign and malignant), renal artery stenosis, sickle cell nephropathy, and renal cortical necrosis.

Normal Renal Vascular Anatomy

• The renal hilum vasculature includes both arteries and veins.
• Renal artery branches proceed sequentially from interlobar arteries to arcuate arteries, then to cortical radial (interlobular) arteries, afferent arterioles, efferent arterioles, and finally to peritubular capillaries or vasa recta.
• Renal veins drain blood from the vasa recta, cortical radial venules/veins, arcuate veins, interlobar veins, and segmental veins.

Introduction to Renal Diseases

• Renal diseases and numerous systemic disorders can affect the renal vasculature.
• Hypertension impacts renal vessels, and renal vascular changes can exacerbate hypertension.
• Kidney diseases serve as both cause and effect of increased blood pressure.

Benign Nephrosclerosis (Hypertensive Nephrosclerosis)

• This is a renal pathology associated with sclerosis of renal arterioles and small arteries.
• Focal ischemia occurs in the parenchyma due to vessels with thickened walls and narrowed lumens.
• Parenchymal effects include glomerulosclerosis and chronic tubulointerstitial injury, which reduces functional renal mass.
• Lesions are more prevalent with advanced age and in Black individuals, even without hypertension, however hypertension and diabetes mellitus exacerbate lesions.

Pathogenesis of Nephrosclerosis

• Hypertension is defined as sustained systolic blood pressure above 140mmHg and diastolic blood pressure above 90mmHg.
• Two processes contribute to nephrosclerosis: medial and intimal thickening as a response to hemodynamic changes (hypertension, aging, genetic defects) and hyaline deposition in arterioles.
• Hyaline deposition is due to extravasation of plasma proteins through injured endothelium and increased deposition of basement membrane matrix.

Morphology of Nephrosclerosis

• Kidneys may appear normal or moderately reduced in size, weighing between 110 and 130 grams.
• The condition usually affects both kidneys.
• Cortical surfaces exhibit fine, even granularity resembling grain leather, and may have occasional coarse scars.
• A cut section reveals a thinned cortex.

Histology of Nephrosclerosis

• Histologic examination shows narrowing of the lumens in arterioles and small arteries due to thickening and hyalinization of the walls (hyaline arteriolosclerosis).
• Microscopic subcapsular scars with sclerotic glomeruli and tubular dropout alternate with better-preserved parenchyma, corresponding to the fine surface granulations.
• Interlobular and arcuate arteries show medial hypertrophy, reduplication of the elastic lamina, and increased myofibroblastic tissue in the intima, leading to Fibroelastic hyperplasia and narrowing of the lumen.
• The glomerular tuft may be obliterated by a dense, eosinophilic globular mass within the Bowman capsule.
• Tubular atrophy occurs as a result of glomerulus destruction.
• Affectation pattern depends on the size of the vessel involved.
• Large arteries down to the arcuate arteries show fibrotic thickening of the intima, replication of the elastica, and partial replacement of the muscularis with fibrous tissue.
• Arterioles display concentric hyaline thickening of the wall with loss of smooth muscle cells or their displacement to the periphery, known as hyaline arteriolosclerosis.

Clinical Features of Nephrosclerosis

• Ordinarily, it is not associated with significant abnormalities of renal function, and renal insufficiency or uremia are uncommon in uncomplicated benign cases.
• Few patients develop progressive renal failure that may lead to end-stage renal disease.
• There are moderate reductions in renal blood flow, but the GFR is typically normal or only slightly reduced.
• Mild proteinuria may occur occasionally.
• African descent, more severe blood pressure elevations, and presence of a second underlying disease like diabetes increase the risk of developing renal failure.
• Renal insufficiency may arise after prolonged benign hypertension or result from the development of the malignant or accelerated phase of hypertension.

Malignant Nephrosclerosis

• This is a form of renal disease associated with the malignant or accelerated phase of hypertension and can develop in previously normotensive individuals.
• It is often superimposed on pre-existing essential benign hypertension, secondary forms of hypertension, or underlying chronic renal disease such as glomerulonephritis or reflux nephropathy.
• Malignant hypertension is a frequent cause of death from uremia in individuals with scleroderma.
• Malignant hypertension occurs in 1% to 5% of all people with elevated blood pressure and affects younger individuals, men, and Black individuals more often.
• Characterized by systolic blood pressure over 200mmHg and diastolic pressure over 120mmHg, retinal vascular changes, papilledema, and renal functional impairment.

Pathogenesis of Malignant Hypertension

• Pathogenesis is not completely clear, but involves microvascular vasoconstriction and injury to the endothelium due to extremely high blood pressure.
• At sites of vascular injury, plasma constituents leak into the arterioles resulting in fibrinoid necrosis, arteries resulting in edematous intimal thickening, and into the subendothelial zone of the glomerular capillaries leading to glomerular consolidation.
• Thrombosis can result in focal cortical necrosis-infarct at vascular injury sites.

Morphology of Malignant Hypertension

• Kidney size depends on the duration and severity of the hypertensive disease.
• Small, pinpoint petechial hemorrhages may appear on the cortical surface due to rupture of arterioles or glomerular capillaries, giving the kidney a "flea-bitten" appearance.
• The cut surface reveals a mottled red-brown and yellow appearance with occasional small cortical infarcts.

Histology of Malignant Hypertension

• Histology reveals fibrinoid necrosis of arterioles (appears as an eosinophilic granular change in the blood vessel wall, representing an acute event).
• Hyperplastic arteriolitis involves proliferation of concentrically arranged smooth muscle cells with layering of collagen (onion skinning) in interlobular arteries/arterioles, which correlates with renal failure in malignant hypertension.
• Electron microscopy shows electron-luscent expansion of the subendothelial zone in glomeruli.
• Immunofluorescence microscopy shows focal exudation of plasma proteins into the injured vessel wall.
• Observed changes are identical to those found in other forms of thrombotic microangiopathy.

Clinical Features of Malignant Hypertension

• The full-blown syndrome is characterized by systolic P >200 mm Hg and diastolic P > 120 mm Hg, papilledema, retinal hemorrhages, encephalopathy, cardiovascular abnormalities, and renal failure.
• Early symptoms relate to increased intracranial pressure, including headaches, nausea, vomiting, visual impairments, and scotomas or spots before the eyes.
• There is marked proteinuria and microscopic or macroscopic hematuria.
• Progressive deterioration of renal function develops if malignant hypertension persists.
• It is a medical emergency requiring aggressive antihypertensive therapy to prevent irreversible renal lesions.
• Malignant hypertension was associated with a 50% mortality rate within 3 months of onset, progressing to 90% within a year in the past.
• Currently, about 75% of patients survive 5 years, and 50% survive with restoration of pre-crisis renal function.

Sickle Cell Nephropathy

• In addition to haematological abnormalities the most manifestations of SCD and the sickle cell trait, appear, in the kidney.
• The interstitial tissue where the vasa recta course is hypertonic and has a low oxygen tension.
• Erythrocytes in the vasa recta sickle and occlude the lumen.
• This can result in infarcts in the medulla and the papillae.
• Severe cases may cause papillary necrosis.
• Ischemic scarring of the medulla leads to focal tubular loss and atrophy.
• Glomeruli get conspicuously congested with sickle cells.
• Focal segmental glomerulosclerosis or, less commonly, membranoproliferative GN occurs in a minority of patients and possibly causes nephrotic syndrome.

Bilateral Cortical Necrosis

• This involves ischemic necrosis of part or all of the renal cortex, sparing the medulla.
• The term infarct indicates one or a few areas of necrosis due to artery occlusion, while cortical necrosis implies more widespread ischemic necrosis.
• Abruptio placentae used to be the most common clinical condition.
• Can also complicate any clinical condition associated with hypovolemic or endotoxic shock
• All forms of shock are associated with ATN, so there is an overlap between that condition & cortical necrosis, both clinically & pathologically.
• Vasa recta supplying medullary arterial blood originate from juxtamedullary efferent arterioles, proximal supplying the outer cortex.
• Occlusion of the outer cortical vessels leads to cortical necrosis and sparing of the medulla.
• Vasoconstrictors like vasopressin and serotonin produce experimental cortical necrosis.

Morphology of Bilateral Cortical Necrosis

• The extent of necrosis varies from patchy to confluent.
• The mildest form is characterized by scattered areas of cortical necrosis less than 1 mm in diameter.
• In severely involved areas, all parenchymal elements have coagulative necrosis.
• Proximal convoluted tubules are invariably necrotic, and most distal tubules are affected.
• Glomeruli and DCT remain unaffected in viable portions of the cortex, but many PCT are necrotic.
• With more extensive necrosis, the cortex shows marked pallor.
• Cortex is diffusely necrotic, except for thin rims of viable tissue beneath the capsule and at the corticomedullary junction.
• Survivors may develop striking dystrophic calcification in necrotic areas.

Clinical Features of Bilateral Cortical Necrosis

• Severe cases manifest as acute renal failure (ARF).
• ARF may be indistinguishable from that produced by acute tubular necrosis (ATN).
• A renal arteriogram or biopsy may be required for diagnosis.
• Recovery depends on the extent of the disease, with a significant incidence of hypertension among survivors.