HYPERTENSION• Definition: diastolic > 90 mm Hg or systolic > 140 mm Hg

pre-hypertension: 120/80 – 139/89

• Prevalence: •20-25% population•4th and later decades•60% population after age 70•Approximately 72 million in US

• Complications: CVA, LVH and CHF, coronary artery disease, renal disease

Renal Vascular DiseasesGENERAL OUTLINE

I. Hypertension

II. “Benign” Nephrosclerosis

III. “Malignant” Nephrosclerosis

IV. Renal Artery Stenosis

V. Thrombotic Microangiopathies

VI. Miscellaneous Vascular Diseases

TYPES OF HYPERTENSION

• Primary Hypertension (Idiopathic) (could be genetic/polymorphisms w/mutations of Na Channels (90 - 95%)

• Secondary Hypertension (5 - 10%)

Renal

Acute Glomerulonephritis Chronic Renal Disease Polycystic Disease Renal Artery Stenosis Renal Vasculitis Renin-producing Tumors (Juxtaglomerular Tumor)Juxtaglomerular Tumor)

EndocrineCardiovascular

Neurologic

BP:Regulated by adjustments to CO and peripheral resistance. CO is influenced by blood volume. Blood volume is controlled by Na concentrations which is a major function of the kidney!

Consequences of HTN:1.Cardiac disease and stroke2.Renal and retinal disease (half die of cardiac disease, 15% cerebrovascular accident, 10% renal failure)3.HTN primary renal injury ESRD

Renal Vascular DiseasesChronic “Benign” Nephrosclerosis

DefinitionSclerosis of small arteries/arterioles w/ attendant renal parenchymal (glomerular and tubulointerstitial) changes.

Clinical FeaturesMild sustained hypertension of long duration.

PathogenesisHemodynamic changes, genetic defects or both resulting in abnormalities in the wall of small arteries and arterioles (medial and intimal thickening, hyaline deposition).

PathologyGross: finely granular contracted kidney. Shallow scars, thinned cortex.Microscopic:1.medial, intinal fibrotic thickening of small arteries. Reduplication of lamina elastica interna, medial hypertorphy w/ luminal narrowing.2.Hyaline deposition in arterioles (accumulation of plasma proteins in BM) w/ loss or displacement of smooth muscle3.Glomeruli w/ ischemic collapsing changes or global glomerulosclerosis (BM is wrinkled)4.Tubular atrophy and interstitial fibrosis

CourseRenal insufficiency/failure if hypertension is prolonged, or if superimposed upon an underlying disease (diabetes).

African-Americans more susceptible to develop ESRD.

Primary (aka essential) hypertension is probably due to a combination of genetic factors and environmental factors:

genetic; environmental; habits such as smoking, diet, alcohol; occupation; living conditions; and a host of other factors

Essential hypertension is mainly treated by adjusting these factors, for example, reducing dietary intake of salt, performing moderate exercise, improve living

conditions and in unresponsive cases, supplemented by antihypertensive drugs such as diuretics and ACE inhibitors.

The main causes of secondary hypertension are: Renovascular Disorder, Renal Parenchymal Disease, Coarctation of the Aorta, Pheochromocytoma ,

Pregnancy Induced Hypertension.

Renal Vascular Diseases“Malignant” Nephrosclerosis

DefinitionSevere hypertension

Systolic >200 mm Hg, diastolic > 120 mm Hg

Acute tissue injury in multiple organs

Clinical FeaturesMen > women, around 40 years of age. (seen more in young African A. males)

Prior history of essential hypertension

HTN BP>200/130papilledema, retinal hemorrhageneurologic symptoms, hematuria, proteinuria, headache, congestive heart failureacute renal failure

PathogenesisUnknown

Vascular chagnes due to preceding HTN complicated by renal ischemia, microvascular vasoconstriction endothelial injury and activation of RAAS.Most patients have high plasma renin.

PathologyGross: variable size, petechial subcapsular hemorrhage, mottling, occasional infarctsMiccroscopic: •Fibrinoid necrosis of arteriles•Intimal edema•hyperpalstic arteriolar changes (“onion skinning”) in chronic injury•glomerular chagnes (necrotizing glomerulitis•thickening and wrinkling of glomerular capillary from hypoperfusion•Thrombosis of small vessels and capillaries.

CourseA medical emergency. Unattended patients may succumb to CVA, ARF or CHF within wks or mo. Treated, 75% will survive 5 yrs. Recovery may occur with renal dysfunction.

Young black men most commonly affected. Also women with toxemia of pregnancy, or persons with renal artery stenosis. Autoimmune diseases can also associate

with mHtn.

Wrinkled

Glomerulous

Renal Vascular DiseasesRenal Artery Stenosis

DefinitionRenal disease associated w/ stenosis of renal artery. 2-5% of hypertension

Clinical Features2-5% of hypertension.HTN in young (fibromuscular dysplasia), or senior adults (atheromatous plaque) w/ preserved renal function.Usually unilaterial w/Bruit.Confused with essential HTN in adults .Renal angiogram is diagnostic and can stent open.Kidney on side of stenosis is small.Plasma renin increased due to hypersecretion from stenotic side.

Pathogenesis

Goldblatt type hypertension

Ischemia activates renin-angiotensin system

Causes:•Atherosclerotic (senosis) •Fibromuscular dysplasia (Intima, Media, Adventitia)•Arteritis•Arterial dissection

Pathology

Stonotic side: kidney is grossly small but smooth. Diffuse ischemic atrophy of tubules and interstitium w/crowding of glomeruli.

Contrlateral Kidney: Features of benign nephrosclerosis

Course•Unattended progressive loss of renal function (stenotic side).•Features of hypertension on contralateral•Nephrectomy, angioplasty curative (70 - 80%).

RAS - AtherosclerosisRAS - Atherosclerosis

Crowded Glomeruli

Crowded Glomeruli

RAS - Hyperplasia of JGARAS - Hyperplasia of JGA

Renal Vascular DiseasesThrombotic Micro-angiopathies

DefinitionGroup of renal diseases having in common thrombosis of small arteries and capillaries with microangiopathic hemolytic anemia and renal insufficiency or renal failure

Clinical Features•Classic HUS: Childhood hemolytic uremic syndrome (HUS) (infectious; E.coli O157:H7) (GI infection w/microganiopathic anemia, renal involvement, renal failure.•Adult HUS: (infections E.coli, shigella, drugs, anti-phospholipid Ab, hypercoagulable)•Familial HUS: mutation in Factor H•Idiopathic Thrombotic Thrombocytopenic Purpura (TTP) systemic thrombotic and purpuric lesions, neurlogical symptoms predominate

Pathogenesis•Endothelial injury and activation, platelet aggregation and vascular thrombosis and/or vasospasm

•HUS - Shiga toxin (injury to endothelial cell and platelet activation) associated with decreased fibrinolysis

•TTP – Inherited mutation of Factor H. Other cases have unusually large von Willebrand factor; metalloproteinase deficiency (ADAMTS13)

PathologyAcute phase dominated by thrombotic changes, and chronic with vascular repair/remodeling1.Thromboic changes and fibrin depostion in wall of interlobular ateries, afferent and glomerular capillaries (double contour appearance)2.Organizing/remodeling chagnes in intralobular arteries, afferent and flomerular capillaries3.Cortical necrosis/infarcts

Course•Renal failure requiring dialysis

• Long term prognosis depends on extent of initial injury & adequacy of management

• 1/3 of patients recover renal function and 1/2 go into CRF

• TTP requires plasmapheresis to remove large von Willebrand factors

Childhood HUS: verotoxin from E. Coli

Adult HUS: causative agent varies – infections, chemo, radiation, pregnancy related, anti-phospholipid antibodies.

Familial HUS: mutation in Factor H

TTP: deficiency of metalloproteinase for von Willebrand factor

OTHER MISCELLANEOUS Renal Vascular DiseasesRenal Embolism•Secondary to heart/valvular disease, aortic catheterization, or trauma•Small are asymptomatic but large result in hematuria or occlusion. •Cause renal infarctions from inconsequential to loss of kidney (arterial is pale, venous is hemorrhagic)•Atheromatous embolization results in occlusion of smaller vessels by embolic material (fiberous deposit post occlusion) followed by giant cell reaction within two week. •Infective endocarditis may cause septic embolization and renal infection, pyelonephritis.

Sickle Cell Nephropathy•Homo or heterozygous individual with hematuria and progressive decrease in concentrating urine due to sickling of red cells (perticularly in hypozic renal medulla)•Intravascular thrombosis results in glomerular changes (focal segmental glomeruloscelerosis and less common membranoproliferative glomerulonephitis), ischemic scarring of medulla, infarcts and papillary necrosis•Can cause proteinuria or hematuria•Prone to medullary fibrosis.•Iron deposits from hemolysis

Atheroembolic Renal Disease

Atheroembolic Renal Disease

Segmental sclerosisSegmental sclerosis

Sickle cell

nephropathy

OTHER MISCELLANEOUS Renal Vascular DiseasesCortical Necrosis•Ischemic necrosis or part of all of the renal cortex secondary to thrombosis and/or vasospasm associated with shock, sepsis, obstetric emergencies (blood loss), and trauma.•Intravascular thrombi may be present•Diffuse: permanent renal failure will result. •Focal: reanl function will be predicated on extent of involvement•Infarct in cortex can lead to ESRD•Pale/Homogeneous necrosis of cortical membrane

OTHER MISCELLANEOUS Renal Vascular DiseasesRenal Artery Thrombosis•Usually complication of atherosclerosis, vascular surgery (correction of stenosis, renal transplant, dissecting aneurysm or aorta, and rarely arteritis).•Partial Thrombosis flank pain, hematuria, w/ HTN to follow.•Complete Occlusion (and bilateral involvement) anuria followed by acute renal failure. Surgery may salvage kidney.

Renal Vein Thrombosis•Unilateral or bilateral, renal vein thrombosis is a complication of hypercoagulable states•Prone to occur in patients with nephrotic syndrome (40%)•Can occur in patients with retroperitoneal infection or tumor, trauma, pancreatitis, and severe dehydration in young children.•Hematuria, anuria, and acute renal failure can be presenting symptoms.•Grossly large, swollen, hemorrhagic•Micro vascular congestion, edema, hemorrhage

Renal Vein Thrombosis

Renal Vein Thrombosis