• intravascular volume which is intimately tied to sodium regulation

• arterial lumen size, which is tightly regulated by neural and hormonal factors

CO

peripheral resistance

• RAA system
• vasodepressor substances (ex: PG's, urinary kallikerin-kinin system, PAF, nitrate)
• decrease GFR
  • increase sodium reabsorption at PCT
  • expands volume and CO
• ANF- decrease sodium reabsorption at DCT, thereby decreasing CO

• raises arterial bp by:
  • direct vasoconstriction
  • increase Ald production
• stimulates production of endothelin, which aslo causes vasoconstriction and leads to medial hypertrophy of arteries and arterioles
• stimulate TGFβ production, which cause progressive fibrosis seen in renal parenchyma and vessels in HTN

• intimal and medial fibrosis
• hyaline arteriosclerosis
• glomerulosclerosis

renal insufficiency

dialysis

• HTN will cause many more sclerotic lesions than age
  • increase depends on degree and duration of HTN
  • usually, lesions appear before clinical onset of HTN

• morphology- glassy pink thickening of tunica media in arterioles (may or may not be circumferential)
• cause- insudation of proteins into the vessel wall due to elevated circumferential tension and endothelial damage

• lumenal pressure
• ability of smooth muscle to contract against the lumenal pressure
• constant relating to radius cubed (Laplace's law)
  • clinical application- small changes in radius produce large changes in circumferential tension

• first lesions in dilated arterioles overlying areas of attentuation in medial smooth muscle
  • lumen is not narrowed at this point and may be larger in diameter than normal arteriole
  • deposits are considered compensatory mechanism to reduce wall tension

• smooth muscle degenerated leads to increased radius (contractile mechanism is uneffective)
• increase in radius leads to marked increase in circumferential tension
• this will also cause increase in permeability of cells
• proteins can now escape from subendothelial space
• this causes lesions under microscope

• fibroelastic tissue appearance deposited progressively on intima (tissue produced by myofibroblasts)
• the above leads to laminated appearance
• myofibroblasts may be visualized in the CT of the vessel

• larger caliber arteries like arterioles and large arteries

1. myofibroblasts produce fibroelastic tissue that is deposited into the intima
2. at the same time myofibroblasts are depositing their tissue, medial smooth muscle cells produce increasing amounts of collagen
3. this collagen is slowly replaced by a scar

• in the areas of greatest smooth muscle atrophy
• smooth muscles respond to excess stretch by the elaboration of collagen

• breakdown in communication between endothelium and smooth muscle
• increased areas of permeability
• innate differences

• ischemic global sclerosis with shrinkage of tuft and replacement by acellular collagen
• focal segmental necrosis- similar to primary FSGS

any tissue that has greatest share of arterial blood flow

• heart
• brain
• kidneys
• arteries themselves

• accelerates rate of formation of atherosclerosis (more specifically at the small vessels causing hyaline arteriosclerosis)
  1. direct damage to endothelial cell
  2. cell responds to endothelial injury
     1. macrophages, platelests adhere to damaged endothelium
     2. release of cytokiines lead to hyperplasia of medial smooth muscle cells
     3. smooth muscle cells migrate to tunica intima
     4. cholesterol enter smooth muscle cells and macrophages creating foam cells
     5. smooth muscle cells release cytokines that produce ECM
  3. development of fibrous cap aka plaque
• hyaline arteriosclerosis causes narrowing of lumen and ischemic damage to tissues they supply
• could potential cause aortic dissection

• seen in retinal arterioles via fundoscope examination
• histologically in many organs, esp. kidney

• left ventricular hypertrophy (can also cause risk of MI, although this is not the most commonly seen cardiac problem)
• pathophysiology
  1. body senses increased pressure and begins to grow the heart in order to adapt to increased arterial pressure
  2. increased myocardial mass requires increased oxygen delivery to heart
  3. this increased demand for oxygen becomes less feasible, and eventually leads to CHF

1. gradual weakening of small arterioles, particularly in basal ganglia
2. leads to formation of microaneurysms (Charcot-Bouchard aneurysms) that could rupture spontaneously
3. this would cause intracerebral hemorrage
4. this would also increase atherosclerosis which would increase risk of cerebral infarction
5. if you progress to malignant HTN, you would cause direct bv damage that would disrupt the BBB, causing an acute edema of the brain called hypertensive encephalopathy

nephrosclerosis

renal failure

• adult polycystic kidney disease
• renal A. stenosis

• vague abdominal pain
• small amounts of blood in urine
• palpably enlarged kidney in thinner patients
• may initially come in for medical attention due to HTN

1. reduced blood flow to kidney
2. activates RAAS
3. increases Ald, leading to increase in salt and water retention

• in young individuals (teen-30), especially women, you will see fibromuscular dysplasia
  • deformation in wall of renal A.
  • usually one kidney is affected (unilat.)
• in older people, esp. men, you will see atherosclerosis
  • location- ostium or the renal A. itself causing the narrowing
  • usually both kidneys affected (bilat.)

• hypokalemia (due to increased Ald), esp. when on a low salt diet
• vascular murmor/bruit can be heard over abdomen (turbulent blood flow)
• renal function worsen with treatment with ACE inhibitors (potential diagnositc test)
• if atheroscleorosis the cause, HTN that is unresponsive to medication

• remove stenosis by fracturing area of narrowing with percutaneous angioplasty
  • with bilateral disease, this therapy is less curative
  • the longer renin is elevated (regardless of what type of cause it is), the more damage occurs to renal tissue and less likely surgery will be effective
  • in order to det. who benefits, measure renin conc. in renal V.
    • if gradient is >1.5 or 2:1, the surgery will likely cure the HTN

• irregular granularity to cortical surface caused by alternating areas of preserved renal parenchyma and atrophic renal tissue

• definition- mult. small areas of ischemic necrosis, chararacteristically in outermost renal cortex,
• cause- hyaline arteriosclerosis induced by HTN 
• prognosis- cause gradual loss of functiong nephrons that leads to progressive renal insufficiency over a period of years

1. initially, high pressure cause progressive medial hyperplasia of medium sized arterioles termed hyperplastic arteriolitis
   • leads to concentric thickening of wall aka "onion skinning"
   • causes further reduction of blood flow
   • induces more renin production causing more increases in bp
2. eventually, vascular necrosis (necrotizing arteriolitis) cause acute interuption in blood flow and areas of infarction

• def.- rapidly progressive raising of bp where kidney is target of increasing damage and cause of rapidly increasing bp
• prognosis- fatal in 1-2 yrs

• tx- aggressive tx in hospital
• prognosis after tx- breaks cycle before extensive tissue necrosis occurs
  • often successful in reversing arteriolitis and HTN