Chapter 11 – Blood Vessels: Hypertensive Vascular Disease Flashcards
What is the consequence of hypotension?
Low pressures (hypotension) result in **inadequate organ perfusion** and can **lead to dysfunction or tissue death**.
What is the consequence of hypertension?
Conversely, high pressures (hypertension) can
cause vessel and end-organ damage.
Like height and weight, blood pressure is a continuously distributed variable, and detrimental
effects of blood pressure increase continuously as the pressure rises; no rigidly defined
threshold level of blood pressure distinguishes risk from safety. Nevertheless, according to the
National Heart, Lung, and Blood Institute of the U.S.A. what range is associated with atherosclerosis?
sustained diastolic pressure greater
than 89 mm Hg, or asustained systolic pressure in excess of 139 mm Hg, are associated with a
measurably increased risk of atherosclerosis, and are therefore felt to represent clinically
significant hypertension
Both the systolic and diastolic blood pressure are important in determining cardiovascular risk.
T or F
True
Both the systolic and diastolic blood pressure are important in determining cardiovascular risk. [19]
By either criterion, some 25% of individuals in the general population are hypertensive.
However, it must be emphasized that these cut-offs are somewhat
arbitrary, and in patients with other risk factors for vascular disease such as diabetes, lower
thresholds are applicable.
Although we have an improved understanding of the molecular pathways that regulate normal
blood pressure, [20,] [21] the mechanisms that result in hypertension remain largely unknown in
most individuals.
T or F
True
Typically, for individuals with such “essential hypertension,” the best we can
say is that the disorder is multifactorial, resulting from the combined effects of multiple genetic
polymorphisms and interacting environmental factors
What is the epidemiology of hypertension?
The prevalence and vulnerability to complications of hypertension increase with age; they are
also higher in African Americans
hypertension is one of the major risk
factors for atherosclerosis and underlies numerous other diseases
T or F
True
It can cause—among other
things—cardiac hypertrophy and heart failure (hypertensive heart disease, Chapter 12 ), multiinfarct
dementia ( Chapter 28 ), aortic dissection, and renal failure
Unfortunately, hypertension
typically remains asymptomatic until late in its course and even severely elevated pressures
can be clinically silent for years.
T or F
True
Left untreated, roughly half of hypertensive patients die of
ischemic heart disease (IHD) or congestive heart failure, and another third die of stroke.
Prophylactic blood pressure reduction dramatically reduces the incidence and death rates from
all forms of hypertension-related pathology.
What is the approximately underlying cause of 5% of patients with renal or adrenal disease?
A small number of patients (approximately
5%) have underlying renal or adrenal disease (such as primary aldosteronism, Cushing
syndrome, pheochromocytoma), narrowing of the renal artery, usually by an atheromatous
plaque (renovascular hypertension) or other identifiable cause (secondary hypertension).
What is the 95% cause of patients with hypertension?
However, about 95% of hypertension is idiopathic (called essential hypertension).
What is essential hypertension?
This form of
hypertension generally does not cause short-term problems.
When controlled, it is compatible
with long life and is asymptomatic, unless a myocardial infarction, cerebrovascular accident, or
other complication supervenes.
TABLE 11-2 – Types and Causes of Hypertension (Systolic and Diastolic
(90% TO 95% OF CASES)
ESSENTIAL HYPERTENSION
TABLE 11-2 – Types and Causes of Hypertension (Systolic and Diastolic
SECONDARY HYPERTENSION
- Renal
- Endocrine
- Cardiovascular
- Neurologic
TABLE 11-2 – Types and Causes of Hypertension (Systolic and Diastolic
SECONDARY HYPERTENSION
Renal
- Acute
- glomerulonephritis
- Chronic renal disease
- Polycystic disease
- Renal artery stenosis
- Renal vasculitis
- Renin-producing tumors
TABLE 11-2 – Types and Causes of Hypertension (Systolic and Diastolic
SECONDARY HYPERTENSION
Endocrine
- Adrenocortical hyperfunction (Cushing syndrome, primary aldosteronism, congenital adrenal hyperplasia, licorice ingestion)
- Exogenous hormones (glucocorticoids, estrogen [including pregnancy-induced and oral contraceptives], sympathomimetics and tyramine-containing foods, monoamine oxidase inhibitors)
- Pheochromocytoma
- Acromegaly
- Hypothyroidism (myxedema)
- Hyperthyroidism (thyrotoxicosis)
- Pregnancy-induced
TABLE 11-2 – Types and Causes of Hypertension (Systolic and Diastolic
SECONDARY HYPERTENSION
Cardiovascular
- Coarctation of aorta
- Polyarteritis nodosa
- Increased intravascular volume
- Increased cardiac output
- Rigidity of the aorta
TABLE 11-2 – Types and Causes of Hypertension (Systolic and Diastolic
SECONDARY HYPERTENSION
Neurologic
- Psychogenic
- Increased intracranial pressure
- Sleep apnea
- Acute stress, including surgery
What is accelerated or malignant
hypertension?
A small percentage, perhaps 5%, of hypertensive persons show a rapidly rising blood pressure
that, if untreated, leads to death within a year or two. Called accelerated or malignant
hypertension, this clinical syndrome is characterized by severe hypertension (i.e., systolic
pressure over 200 mm Hg, diastolic pressure over 120 mm Hg), renal failure, and retinal
hemorrhages and exudates,with or without papilledema.
It may develop in previously
normotensive persons but more often is superimposed on pre-existing benign hypertension,
either essential or secondary
What is BP?
Blood pressure is a function of cardiac output and peripheral vascular resistance ( Fig. 11-4A
), two hemodynamic variables that are influenced by multiple genetic, environmental, and
demographic factors.
What are the major factors that determine BP?
- age,
- gender,
- body mass index,
- and diet, particularly sodium intake.
FIGURE 11-4 Blood pressure regulation.
A, The critical roles played by cardiac output and
peripheral resistance in modulating blood pressure.
B, Interplay of renin-angiotensinaldosterone
and atrial natriuretic peptide in maintaining blood pressure homeostasis.
Cardiac output is dependent on what?
Cardiac output is highly dependent on blood volume, itself greatly influenced by the sodium
homeostasis.
Peripheral vascular resistance is determined mainly at what level?
Peripheral vascular resistance is determined mainly at the level of the arterioles
and is affected by neural and hormonal factors.
What balance the normal vascular tone?
-
humoral vasoconstricting influences
- (including angiotensin II, catecholamines, and
endothelin) and
* vasodilators (including kinins, prostaglandins, and NO).
How do resistance vessels exhibit autoregulation?
Resistance vessels
also exhibit autoregulation, whereby increased blood flow induces vasoconstriction to protect
against tissue hyperperfusion.
What are the other local factors that are also important in regulating blood pressure?
- pH and hypoxia,
- and the α- and β- adrenergic systems, which influence heart rate, cardiac contraction, and vascular tone, may
The integrated function of these systems
ensures adequate perfusion of all tissues, despite regional differences in demand.
The kidneys play an important role in blood pressure regulation as follows ( Fig. 11-4B ):
- renin-angiotensin system
- kidney also produces a variety of vascular relaxing, or antihypertensive, substances
- glomerular filtration rate falls,
- Natriuretic factors
How does the RAS regulate blood pressure?
Through the renin-angiotensin system, the kidney influences both peripheral resistance
and sodium homeostasis
. Renin is secreted by the juxtaglomerular cells of the kidney in response to fall in blood pressure.
It converts plasma angiotensinogen to angiotensin I,
which is then converted to angiotensin II by angiotensinconverting enzyme.
Angiotensin
II raises blood pressure by increasing both peripheral resistance (direct action on vascular smooth muscle cells) and blood volume (stimulation of aldosterone secretion, and increase in distal tubular reabsorption of sodium).
The kidney through the RAS regulate the blood pressure by influencing both on what?
- peripheral resistance
- and sodium homeostasis
.
What is renin?
Renin is secreted by the juxtaglomerular cells of the kidney in response to fall in blood pressure.
It converts plasma angiotensinogen to angiotensin I,
which is then converted to angiotensin II by angiotensinconverting enzyme.
Angiotensin
II raises blood pressure by increasing both peripheral resistance (direct action on vascular smooth muscle cells) and blood volume (stimulation of aldosterone secretion, and increase in distal tubular reabsorption of sodium).
RENIN -> converts angiotensinogen to angiotensin I -> angiotensin II by angiotensinconverting enzyme. = INC BP
How does Angiotensis II raises bp?
- increasing both peripheral resistance (direct action on vascular smooth muscle cells) and blood volume (stimulation of aldosterone secretion, and
- increase in distal tubular reabsorption of sodium).
What substances do the kidney produce which presumambly counterbalance the vasopressor effects of angiotensin?
The kidney also produces a variety of vascular relaxing, or antihypertensive, substances (including prostaglandins and NO), which presumably counterbalance the vasopressor (causing the constriction effects of angiotensin)
What does the kidney do when the blood volume is reduced?
When blood volume is reduced, the glomerular filtration rate falls, leading to increased
reabsorption of sodium by proximal tubules, thereby conserving sodium and expanding
blood volume
What is the function of natriuretic factors?
Natriuretic factors, including the natriuretic peptides secreted by atrial and ventricular
myocardiuminresponse to volume expansion,inhibit sodium reabsorption in distal
tubulesandthereby cause sodium excretionanddiuresis.
Natriuretic peptides also
induce vasodilation and may be considered to represent endogenous inhibitors of the
renin-angiotensin system.
From where do natriuretic peptides are secreted?
natriuretic peptides secreted by atrial and ventricular
myocardium in response to volume expansion
What is a definite factor that play a role in determining blood pressure levels?
Genetic factors play a definite role in determining blood pressure levels, as shown by studies comparing blood pressure in monozygotic and dizygotic twins, and other types of family studies, including comparisons of genetically related and adopted family members
How do
single-gene disorders cause relatively rare forms of hypertension (and hypotension)?
) by altering
net sodium reabsorption in the kidney.
The importance of sodium balance is emphasized by
considering that the kidneys filter 170 liters of plasma containing 23 moles of salt daily; on a
typical 100-mEq sodium diet, this means that 99.5% of the filtered salt must be reabsorbed.
About 98% of the filtered sodium is reabsorbed by a number of ion channels, exchangers, and
transporters that are constitutively active and not subject to regulation.
Absorption of the
remaining 2% of sodium occurs via the epithelial Na + channel (ENaC), which is tightly regulated
by the renin-angiotensin system in the cortical collecting tubule; it is this resorption pathway that
determines net sodium balance.
98% of the filtered sodium is reabsorbed by what?
- number of ion channels,
- exchangers, and transporters that are constitutively active and not subject to regulation.
Where does the 2% of remaining sodium occurs?
- via the epithelial Na + channel (ENaC), which is tightly regulated by the renin-angiotensin system in the cortical collecting tubule; it is this resorption pathway that determines net sodium balance.
Single-gene disorders cause severe but rare forms of hypertension through several
mechanisms. These include:
- Gene defects affecting enzymes.
- Mutations affecting proteins that influence sodium reabsorption.
Single-gene disorders cause severe but rare forms of hypertension through several
mechanisms.
What are the Gene defects affecting enzymes?
aldosterone metabolism (e.g., aldosterone synthase, 11β-hydroxylase, 17α-hydroxylase)
These lead to an increase in secretion of
aldosterone, increased salt and water resorption, plasma volume expansion and,
ultimately, hypertension
Single-gene disorders cause severe but rare forms of hypertension through several
mechanisms.
What is an example of the Mutations affecting proteins that influence sodium reabsorption
Liddle syndrome,
What is Liddle syndrome?
moderately severe form of salt-sensitive hypertension, called Liddle syndrome, is
caused by mutations in an epithelial Na + channel protein that lead to increased distal
tubular reabsorption of sodium induced by aldosterone.
Inherited variations in blood pressure may also depend on the cumulative effects of
polymorphisms in several genes that affect blood pressure
T or F
True
. For example, predisposition to
essential hypertensionhas been associated withvariations in the genes encoding components
of the renin-angiotensin system: there is an association of hypertension with polymorphisms in
both the angiotensinogen locus and the angiotensin receptor locus.
Genetic variants in the
renin-angiotensin system may contribute to the known racial differences in blood pressure
regulation
What is a key
initiating event in essential hypertension indeed, a final common pathway for the pathogenesis of hypertension?
Reduced renal sodium excretion in the presence of normal arterial pressure
Decreased sodium excretion may lead sequentially to what?
- increase in fluid volume,
- increased cardiac output,
- and peripheral vasoconstriction,
thereby elevating blood pressure.
At the higher setting of blood pressure, enough additional sodium would be excreted by the kidneys to equal intake and prevent further fluid retention.
Thus, an
altered but steady state of sodium excretion would be achieved (“resetting of pressure natriuresis”), but at the expense of an increase in blood pressure.
What is vasoconstrictive influence?
Vasoconstrictive influences, such as factors that induce vasoconstriction or stimuli that cause
structural changes in the vessel wall, can lead to an increase in peripheral resistance and may
also play a role in primary hypertension.
Moreover, chronic or repeated vasoconstrictive
influences could cause thickening and rigidity of the involved vessels.
What are the Environmental factors can modify the impact of genetic determinants of hypertension?
- Stress,
- obesity,
- smoking,
- physical inactivity, and
- heavy consumption of salt have all been implicated as exogenous factors in hypertension.
Indeed, evidence linking the level of dietary sodium intake with the prevalence of hypertension in different population groups is particularly impressive.
Moreover, in both essential and secondary hypertension, heavy sodium intake augments the condition.
To summarize, essential hypertension is a complex, multifactorial disorder.
Although single
gene disorders can be responsible for hypertension in rare cases, it is unlikely that such mutations are a major cause of essential hypertension.
It is more likely that essential
hypertension results from interactions of mutations or polymorphisms at several loci that
influence blood pressure, with a variety of environmental factors (e.g., stress, salt intake).
Mendelian forms of hypertension and hypotension are rare but yield insights into pathways and
mechanisms of blood pressure regulation, and they may help define rational targets for
therapeutic intervention.
Sustained hypertension requires participation of the kidney, which normally responds to hypertension by eliminating salt and water.
Susceptibility genes for
essential hypertension in the larger population are currently unknown but may well include
genes that govern responses to an increased renal sodium load, levels of pressor substances,
reactivity of vascular smooth muscle cells to vasoconstrictive agents, or smooth muscle cell
growth. In established hypertension, both increased blood volume and increased peripheral
resistance contribute to the increased pressure.
For many of the secondary forms of hypertension, the underlying pathways are reasonably well understood.
For example, in renovascular hypertension, renal artery stenosis causes decreased glomerular flow and pressure in the afferent arteriole of the glomerulus.
This induces what?
- This (1) induces renin secretion, initiating angiotensin II–mediated vasoconstriction and increased peripheral resistance, and (
- 2) increases sodium reabsorption and therefore blood volume through the aldosterone mechanism.
What is one of the most common causes of secondary hypertension ( Chapter 24 )?
Primary hyperaldosteronism
Hypertension not only accelerates atherogenesis (see below) but also causes degenerative
changes in the walls of large and medium arteries that can lead to aortic dissection and
cerebrovascular hemorrhage.
T or F
True
Hypertension is associated with two forms of small blood vessel disease:
- hyaline arteriolosclerosis and
- hyperplastic arteriolosclerosis.
What is Hyaline Arteriolosclerosis?
- Arterioles show homogeneous, pink hyaline thickening with associated luminal narrowing ( Fig. 11-5A ). These changes stem from plasma protein leakage across injured endothelial cells, and increased smooth muscle cell matrix synthesis in response to chronic hemodynamic stress.
- Although the vessels of elderly persons (either normo- or hypertensive) also frequently show hyaline arteriosclerosis, it is more generalized and severe in individuals with hypertension. The same lesions are also a common feature of diabetic microangiography; in that case the underlying etiology is hyperglycemia-induced endothelial cell dysfunction ( Chapter 24 ).
Although the vessels of elderly persons (either normo- or hypertensive) also frequently show hyaline arteriosclerosis, it is more generalized and severe in individuals with hypertension
T or F
True
What does hyaline arteriosclerosis cause in nephrosclerosis due to chronic hypertension?
In nephrosclerosis due to chronic hypertension,
the arteriolar narrowing of hyaline arteriosclerosis causes diffuse impairment of renal blood
supply and causes glomerular scarring
What is yperplastic Arteriolosclerosis?
Hyperplastic Arteriolosclerosis.
This lesion occurs in severe (malignant) hypertension;
vessels exhibit “onion-skin lesions,” characterized by concentric, laminated thickening of the
walls and luminal narrowing ( Fig. 11-5B ).
The laminations consist of smooth muscle cells with
thickened, reduplicated basement membranes; in malignant hypertension they are
accompanied by fibrinoid deposits and vessel wall necrosis (necrotizing arteriolitis), particularly in the kidney.
FIGURE 11-5 Vascular pathology in hypertension
- . A, Hyaline arteriolosclerosis. The arteriolar wall is thickened with increased protein deposition (hyalinized), and the lumen is markedly narrowed.
- B, Hyperplastic arteriolosclerosis (onion-skinning; arrow) causing lumenal obliteration (arrow; periodic acid–Schiff stain)
