HTN and ATHEROSCLEROSIS Flashcards
Malignant Hypertension
If untreated, leads to death in within 1 to 2 years. Such hypertension usually is severe (i.e., systolic pres-
sures over 200 mm Hg or diastolic pressures over 120 mm
Hg) and associated with renal failure and retinal hemor-
rhages, with or without papilledema.
Prognosis
cases (95%) are idiopathic (essential hypertension).
This form is compatible with long life unless a myocardial
infarction, stroke, or another complication supervenes. Most
of the remaining cases (secondary hypertension) are due
to primary renal disease, renal artery narrowing (renovas-
cular hypertension), or adrenal disorders
Secondary HTN
Renal,endocrine,cardiovascular,neurologic
rders include
• Gene defects in enzymes involved in aldosterone
metabolism (e.g., aldosterone synthase, 11β-hydroxylase,
17α-hydroxylase), leading to increased aldosterone secre-
tion, increased salt and water resorption, and plasma
volume expansion
• Mutations in proteins that affect sodium resorp-
tion (as in Liddle syndrome, which is caused by mutations
in ENaC, leading to increased distal tubular resorption of
sodium induced by aldosterone)
Hyaline arteriosclerosis
It is marked by homogeneous, pink hyaline
thickening of the arteriolar walls, with loss of underlying
structural detail, and luminal narrowing (Fig. 9–5, A). The
lesions stem from leakage of plasma components across
injured endothelial cells, into vessel walls and increased ECM
production by smooth muscle cells in response to chronic
hemodynamic stress. In the kidneys, the arteriolar narrowing
caused by hyaline arteriosclerosis leads to diffuse vascular
compromise and nephrosclerosis (glomerular scarring).
Although the vessels of elderly patients (normo- or hyper-
tensive) show the same changes, hyaline arteriolosclerosis is
more generalized and severe in patients with hypertension.
The same lesions also are common in diabetic microangiopa-
thy; in this disorder, the underlying etiology is hyperglycemia-associated endothelial cell dysfunction
Hyperplastic arteriolosclerosis
Hyperplastic arteriolosclerosis is more typical of
severe hypertension. Vessels exhibit “onionskin,” concentric,
laminated thickening of arteriolar walls and luminal narrowing
(Fig. 9–5, B). The laminations consist of smooth muscle cells
and thickened, reduplicated basement membrane. In malig-
nant hypertension these changes are accompanied by fibri-
noid deposits and vessel wall necrosis (necrotizing
arteriolitis), which are particularly prominent in the kidney.
vascular wall response to injury
injury leads to EC loss or dysfunction stimulates SMC growth, ECM synthesis, & thickening of the vascular wall.
migration of SMCs or SMC precursor cells into the intima.
These cells then proliferate and synthesize ECM in much the same way that fi broblasts fill in a wound elsewhere in the body
cells then proliferate and synthesize ECM in much the same way that fi broblasts fi ll in a wound elsewhere in the body forming a neointima that typically is covered by an intact EC layer. Neointimal response occurs with any form of vascular damage or dysfunction, including infection, inflammation, immune injury, physi-cal trauma (e.g., from a balloon catheter or hypertension), or toxic exposure (e.g. oxidized lipids or cigarette smoke).
phenotype of neointimal SMCs is distinct from medial SMCs. Thus, neointimal SMCs are not contractile like medial SMCs,but do have the capacity to divide
Regulated by growth factors and intimal cells
Arteriosclerosis
generic term ref l ecting arterial wall thickening and loss of elasticity.
Arteriolosclerosis affects small arteries and arterioles and may cause downstream ischemic injury.
Mönckeberg medial sclerosis is
characterized by the pres-ence of calcific deposits in muscular arteries, usually centered on the internal elastic lamina, and typically in individuals older than 50 years of age.
Fibromuscular intimal hyperplasia
non-atherosclerotic process that occurs in muscular arteries larger than arterioles. This is predominantly an SMC- and ECM-rich lesion driven by inflammation or by mechanical injury (e.g., associated with stents or bal-loon angioplasty) Such a healing response can cause substantial stenosis of the vessel; indeed such inti-mal hyperplasia underlies in-stent restenosis and is the major long-term limitation of solid organ transplants.
Atherosclerosis,
atheromas (or atheromatous or atherosclerotic plaques) that impinge on the vascular lumen and can rupture to cause sudden occlusion. It causes coronary, cerebral, and peripheral vascular disease, and causes (roughly half of all deaths) in the Western world than any other disorder
Ath-eromatous plaques are raised lesions composed of soft friable (grumous) lipid cores (mainly cholesterol and cho-lesterol esters, with necrotic debris) covered by fi brous caps
As they enlarged, atherosclerotic plaques may mechanically obstruct vascular lumina, leading to stenosis. Of greater concern, however, atherosclerotic plaques also are prone to rupture, an event that may result in thrombosis and sudden occlusion of the vessel.
The thick-ness of the intimal lesions also may be sufficient to impede the perfusion of the underlying media, which may be weakened by ischemia and by changes in the ECM caused by subsequent inf l ammation. Together, these two factors weaken the media, setting the stage for the formation of aneurysms.
Risk Factors
Genetics. Family history is the most important indepen-dent risk factor for atherosclerosis.
Age. Atherosclerosis usually remains clinically silent until lesions reach a critical threshold in middle age or later. Thus, the incidence of myocardial infarction increases 5-fold between 40 and 60 years of age
Gender. All other factors being equal, premenopausal women are relatively protected against atherosclerosis (and its consequences) compared with age-matched men.
Risk Factors modifiable
Modif i able Major Risk Factors • Hyperlipidemia—and, more specif i cally, hypercholes-terolemia—is a major risk factor for development of atherosclerosis and is suff i cient to induce lesions in the absence of other risk factors.
High dietary intake of cholesterol and saturated fats (e.g., present in egg yolks, animal fats, and butter) raises plasma cholesterol levels.
Omega-3 fatty acids,Exercise,Statins
Hypertension
Cigarette smoking
Diabetes mellitus
Hyperplastic arteriolosclerosis
Hyperplastic arteriolosclerosis is more typical of
severe hypertension. Vessels exhibit “onionskin,” concentric,
laminated thickening of arteriolar walls and luminal narrowing
(Fig. 9–5, B). The laminations consist of smooth muscle cells
and thickened, reduplicated basement membrane. In malig-
nant hypertension these changes are accompanied by fibri-
noid deposits and vessel wall necrosis (necrotizing
arteriolitis), which are particularly prominent in the kidney.
