Chapter 11 – Blood Vessels: Hypertensive Vascular Disease

Question 1

What is the consequence of hypotension?

Answer 1

Low pressures (hypotension) result in **inadequate organ perfusion**
and can **lead to dysfunction or tissue death**.

Question 2

What is the consequence of hypertension?

Answer 2

Conversely, high pressures (hypertension) can
cause vessel and end-organ damage.

Question 3

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?

Answer 3

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

Question 4

Both the systolic and diastolic blood pressure are important in determining cardiovascular risk.

T or F

Answer 4

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.

Question 5

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

Answer 5

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

Question 6

What is the epidemiology of hypertension?

Answer 6

The prevalence and vulnerability to complications of hypertension increase with age; they are
also higher in African Americans

Question 7

hypertension is one of the major risk
factors for atherosclerosis and underlies numerous other diseases

T or F

Answer 7

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

Question 8

Unfortunately, hypertension
typically remains asymptomatic until late in its course and even severely elevated pressures
can be clinically silent for years.

T or F

Answer 8

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.

Question 9

What is the approximately underlying cause of 5% of patients with renal or adrenal disease?

Answer 9

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).

Question 10

What is the 95% cause of patients with hypertension?

Answer 10

However, about 95% of hypertension is idiopathic (called essential hypertension).

Question 11

What is essential hypertension?

Answer 11

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.

Question 12

TABLE 11-2 – Types and Causes of Hypertension (Systolic and Diastolic

(90% TO 95% OF CASES)

Answer 12

ESSENTIAL HYPERTENSION

Question 13

TABLE 11-2 – Types and Causes of Hypertension (Systolic and Diastolic

SECONDARY HYPERTENSION

Answer 13

• Renal
• Endocrine
• Cardiovascular
• Neurologic

Question 14

TABLE 11-2 – Types and Causes of Hypertension (Systolic and Diastolic

SECONDARY HYPERTENSION

Renal

Answer 14

• Acute
• glomerulonephritis
• Chronic renal disease
• Polycystic disease
• Renal artery stenosis
• Renal vasculitis
• Renin-producing tumors

Question 15

TABLE 11-2 – Types and Causes of Hypertension (Systolic and Diastolic

SECONDARY HYPERTENSION

Endocrine

Answer 15

• 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

Question 16

TABLE 11-2 – Types and Causes of Hypertension (Systolic and Diastolic

SECONDARY HYPERTENSION

Cardiovascular

Answer 16

• Coarctation of aorta
• Polyarteritis nodosa
• Increased intravascular volume
• Increased cardiac output
• Rigidity of the aorta

Question 17

TABLE 11-2 – Types and Causes of Hypertension (Systolic and Diastolic

SECONDARY HYPERTENSION

Neurologic

Answer 17

• Psychogenic
• Increased intracranial pressure
• Sleep apnea
• Acute stress, including surgery

Question 18

What is accelerated or malignant
hypertension?

Answer 18

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

Question 19

What is BP?

Answer 19

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.

Question 20

What are the major factors that determine BP?

Answer 20

• age,
• gender,
• body mass index,
• and diet, particularly sodium​ intake.

Question 21

Answer 21

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.

Question 22

Cardiac output is dependent on what?

Answer 22

Cardiac output is highly dependent on blood volume, itself greatly influenced by the sodium
homeostasis.

Question 23

Peripheral vascular resistance is determined mainly at what level?

Answer 23

Peripheral vascular resistance is determined mainly at the level of the arterioles
and is affected by neural and hormonal factors.

Question 24

What balance the normal vascular tone?

Answer 24

• humoral vasoconstricting influences
  
  • (including angiotensin II, catecholamines, and

endothelin) and
* vasodilators (including kinins, prostaglandins, and NO).

Question 25

How do resistance vessels exhibit autoregulation?

Answer 25

Resistance vessels also exhibit autoregulation, whereby **increased blood flow induces vasoconstrictio**n to protect against tissue hyperperfusion.

Question 26

What are the other local factors that are also important in regulating blood pressure?

Answer 26

* **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.

Question 27

The kidneys play an important role in blood pressure regulation as follows ( Fig. 11-4B ):

Answer 27

* renin-angiotensin system * kidney also produces a variety of vascular relaxing, or antihypertensive, substances * glomerular filtration rate falls, * Natriuretic factors

Question 28

How does the RAS regulate blood pressure?

Answer 28

Through the renin-angiotensin system, the kidney i**nfluences both peripheral resistance** and **sodium homeostasi**s . 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).

Question 29

The kidney through the RAS regulate the blood pressure by influencing both on what?

Answer 29

* peripheral resistance * and sodium homeostasis .

Question 30

What is renin?

Answer 30

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**

Question 31

How does Angiotensis II raises bp?

Answer 31

* **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).**

Question 32

What substances do the kidney produce which presumambly counterbalance the vasopressor effects of angiotensin?

Answer 32

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)

Question 33

What does the kidney do when the blood volume is reduced?

Answer 33

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**

Question 34

What is the function of natriuretic factors?

Answer 34

Natriuretic factors, including the **natriuretic peptides secreted by atrial and ventricular myocardium**in**response to volume expansion**,***inhibit sodium reabsorption in distal tubules***and**thereby cause sodium excretion**and**diuresis.** Natriuretic peptides also **induce vasodilation** and may be **considered to represent endogenous inhibitors of the renin-angiotensin system.**

Question 35

From where do natriuretic peptides are secreted?

Answer 35

natriuretic peptides secreted by **atrial and ventricular myocardium in response to volume expansion**

Question 36

What is a definite factor that play a role in determining blood pressure levels?

Answer 36

**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

Question 37

How do **single-gene disorders** cause **relatively rare forms of hypertension (and hypotension**)?

Answer 37

) 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.

Question 38

98% of the filtered sodium is reabsorbed by what?

Answer 38

* number of ion channels, * exchangers, and transporters that are constitutively active and not subject to regulation.

Question 39

Where does the 2% of remaining sodium occurs?

Answer 39

* 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.**

Question 40

Single-gene disorders cause severe but rare forms of hypertension through several mechanisms. These include:

Answer 40

* **Gene defects affecting enzymes**. * **Mutations affecting proteins that influence sodium reabsorption.**

Question 41

Single-gene disorders cause severe but rare forms of hypertension through several mechanisms. What are the Gene defects affecting enzymes?

Answer 41

**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

Question 42

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

Answer 42

Liddle syndrome,

Question 43

What is Liddle syndrome?

Answer 43

**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.**

Question 44

Inherited variations in blood pressure may also depend on the cumulative effects of polymorphisms in several genes that affect blood pressure T or F

Answer 44

True . For example, **predisposition to essential hypertension**has been associated with**variations in the genes encoding components** of the renin-angiotensin system: there is an a**ssociation 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

Question 45

What is a key initiating event in essential hypertension indeed, a final common pathway for the pathogenesis of hypertension?

Answer 45

**Reduced renal sodium excretion** in the **presence of normal arterial pressure**

Question 46

Decreased sodium excretion may lead sequentially to what?

Answer 46

* 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.

Question 47

What is vasoconstrictive influence?

Answer 47

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.

Question 48

What are the Environmental factors can modify the impact of genetic determinants of hypertension?

Answer 48

* 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 differe**nt population groups is **particularly impressive.** Moreover, in **both essential and secondary hypertension, heavy sodium intake augments the condition.**

Question 49

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).

Question 50

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.

Question 51

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.

Question 52

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?

Answer 52

* This (1) **induces renin secretion**, initiating angiotensin II–mediated vasoconstriction and increased peripheral resistance, and ( * 2) **increases sodium reabsorptio**n and therefore blood volume through the aldosterone mechanism.

Question 53

What is one of the most common causes of secondary hypertension ( Chapter 24 )?

Answer 53

Primary hyperaldosteronism

Question 54

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

Answer 54

True

Question 55

Hypertension is associated with two forms of small blood vessel disease:

Answer 55

* **hyaline** arteriolosclerosis and * **hyperplastic** arteriolosclerosis.

Question 56

What is Hyaline Arteriolosclerosis?

Answer 56

* 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 ).

Question 57

Although the vessels of elderly persons (either normo- or hypertensive) also **frequently show hyaline arteriosclerosis, i**t is **more generalized and severe in individuals with hypertension** T or F

Answer 57

True

Question 58

What does hyaline arteriosclerosis cause in nephrosclerosis due to chronic hypertension?

Answer 58

In nephrosclerosis due to chronic hypertension, the arteriolar narrowing of hyaline arteriosclerosis causes **diffuse impairment of renal blood supply and causes glomerular scarring**

Question 59

What is yperplastic Arteriolosclerosis?

Answer 59

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.**

Question 60

Answer 60

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)