• I. Benign Nephrosclerosis
• II. Malignant Nephrosclerosis
• Benign nephrosclerosis is the term used for
the renal pathology associated with
sclerosis (Hardening) of renal arterioles
and small arteries.
• The resultant effect is focal ischemia
of parenchyma supplied by vessels with
thickened walls and consequent
NephrosclerosisThe parenchymal effects include
• chronic tubulointersititial injury,
producing a reduction in functional renal mass.
Hypertension and diabetes
mellitus, increase the incidence and
severity of the lesions.
Two processes participate in the arterial
• I. Medial and intimal thickening,
as a response to hemodynamic changes, aging,
genetic defects, or some combination of
The wall of a blood vessel is composed of 3 layers:
Intima, media & adventitia.
II. Hyaline deposition in
arterioles, caused partly by extravasation
of plasma proteins through injured
partly by increased deposition
of basement membrane
• The kidneys are either normal or moderately
reduced in size, with average weights
between 110 and 130 gm.
• The cortical surfaces have a fine, even
granularity that resembles grain leather.
• The loss of mass is due mainly to cortical
scarring and shrinking.
The weight of one kidney averages about 120-150 g
Size: 12x 6x3 cm.
Close-up of the gross appearance of the cortical surface in
benign nephrosclerosis illustrating the fine, leathery
granularity of the surface.
• Narrowing of the lumens of
arterioles and small arteries,
caused by thickening and hyalinization
of the walls (hyaline arteriolosclerosis)
A fatty deposit
Hyaline: A glass, pink protieinacious material
• Corresponding to the fine surface
• microscopic subcapsular scars
• with sclerotic glomeruli and
• tubular dropout (Foci of tubular
• alternating with better preserved
• The interlobular and arcuate arteries show
a characteristic lesion that consists of
• Medial hypertrophy,
• Reduplication of the elastic lamina, and
• Increased myofibroblastic tissue in the
• which combine to narrow the lumen.
• This change, called fibroelastic hyperplasia
• often accompanies hyalin arteriolosclerosis and
• increases in severity with AGEand
• in the presence of
There is Patchy Ischemic
Atrophy, which consists of
(1) Foci Of Tubular Atrophy and
Interstitial Fibrosis and
(2) A Variety Of Glomerular Alterations.
Glomerular alterations include:
1.Collapse Of The GBM,
2. Deposition Of Collagen Within The Bowman Space,
3. Periglomerular Fibrosis, and
4. Total Sclerosis Of Glomeruli.
• When the ischemic changes
are pronounced and affect large areas of
parenchyma, they can produce
It is unusual for uncomplicated benign
nephrosclerosis to cause renal insufficiency
There are usually moderate reductions in renal
blood flow, but the GFR is normal or only
Three groups of hypertensive patients with benign nephrosclerosis are at
increased risk of developing renal failure:
1. People Of African Descent,
2. People with more severe blood pressure elevations,
3. Persons with a second underlying disease, especially diabetes.
In these groups renal insufficiency may supervene after
prolonged benign hypertension.
• Malignant nephrosclerosis is the
form of Renal Disease associated
with The Malignant or Accelerated
• Malignant hypertension may occasionally
develop in previously normotensive
but often is superimposed on
• Preexisting essential benign hypertension
• Secondary forms of hypertension, or
• An underlying chronic renal
disease, particularly glomerulonephritis or
reflux nephropathy Associated with vesico-ureteric reflux
• It is also a frequent cause of death from
uremia in individuals with scleroderma.
Malignant hypertension is relatively
uncommon, occurring in 1% to 5% of all
people with elevated blood pressure.
• In its pure form it usually affects younger
individuals, and occurs more often in men
and in blacks.
• The basis for this turn for the worse (Zawaal)
in hypertensive subjects is
unclear, but the
following sequence of
events is suggested.
• 1.The initial insult seems to be some form of
vascular damage to the kidneys.
This might result
• from long-standing benign hypertension,
with eventual injury to the arteriolar walls, or
• 2. The initiating injury may spring de novo from
• a coagulopathy, or
• some injury causing acute exacerbation of the hypertension.
• In any case, the result is
• 1. increased permeability of the small
vessels to fibrinogen and other plasma
• 2. endothelial injury,
• 3. focal death of cells of the vascular
• 4. platelet deposition.
• This leads to the appearance of
1. Fibrinoid necrosis of arterioles and small
2. Swelling of the vascular intima, and
3. Intravascular Thrombosis.
• Mitogenic factors from platelets (e.g., PDGF),
plasma, and other cells cause hyperplasia of
intimal smooth muscle of vessels, resulting in
the hyperplastic arteriolosclerosis that is
typical of malignant hypertension and further
narrowing of the lumens.
• The kidneys become
• With severe involvement of the renal
afferent arterioles, the renin-angiotensin
system receives a powerful stimulus;
indeed, patients with malignant
hypertension have markedly elevated levels
of plasma renin.
• This sets up a self-perpetuating cycle in which
angiotensin II causes intrarenal
vasoconstriction, and the attendant renal
ischemia perpetuates renin secretion.
• Other vasoconstrictors
(e.g., endothelin) and loss of
vasodilators (nitric oxide) may
also contribute to
• Aldosterone levels are also
elevated, and salt retention
undoubtedly contributes to the
elevation of blood
• The consequences of the markedly elevated
blood pressure on the blood vessels
throughout the body are known as
the renal disorder is malignant
• On gross inspection the kidney size
depends on the duration and severity of the
• Small, pinpoint petechial HEMORRHAGES
may appear on the cortical surface from
RUPTURE of arterioles or glomerular
capillaries, giving the kidney a peculiar
• Two histologic alterations characterize blood
vessels in malignant hypertension:
1. Fibrinoid necrosis of arterioles.
This appears as an Eosinophilic Granular Change in
the blood vessel wall, which stains positively
for fibrin by histochemical or
• This change represents an acute event; it may
be accompanied by limited inflammatory
infiltrate within the wall.
• Sometimes the glomeruli become necrotic
and infiltrated with neutrophils, and the
glomerular capillaries may thrombose.
2. In the interlobular arteries and arterioles, there
is intimal thickening caused by a proliferation of
elongated, concentrically arranged smooth
muscle cells, together with fine concentric
layering of collagen and accumulation of pale-
staining material that probably represents
accumulations of proteoglycans and plasma
proteins. This alteration has been referred to as
because of its concentric appearance.
• The lesion, also called hyperplastic
arteriolitis, correlates well with renal failure
in malignant hypertension.
• There may be superimposed intraluminal
• The arteriolar and arterial lesions result in
considerable narrowing of all vascular
lumens, ischemic atrophy and, at
times, infarction distal to the abnormal
• SP>200 mm Hg & DP>120 mm Hg,
• Retinal hemorrhages,
• Cardiovascular abnormalities, &
• Renal failure.
• Most often, the early symptoms are related to
increased intracranial pressure and include
• vomiting, and
• visual impairments,
particularly scotomas or spots before the eyes.
are sometimes encountered, characterized by
• episodes of loss of consciousness or
• At the onset of rapidly mounting blood
pressure, there is marked proteinuria
and microscopic or sometimes macroscopic
hematuria but no significant alteration
in renal function.
• Soon, however, renal failure makes its
• The syndrome is
• a true medical emergency requiring
the institution of aggressive and prompt
antihypertensive therapy to
prevent the development of irreversible renal
• Before the introduction of current
antihypertensive drugs, malignant
hypertension was associated with a
• 50% mortality rate within 3 months of
onset, progressing to 90%within a year.
• At present, however,
• about 75% of patients survive 5
years, and 50% survive with
restoration of pre-crisis renal