Regulation of Normal Blood Pressure.

Blood pressure is proportional to cardiac output and peripheral vascular resistance ( Fig. 11-13 ). Indeed, the blood pressure level is a complex trait that is determined by the interaction

of multiple genetic, environmental, and demographic factors that influence cardiac output and vascular resistance. The major factors that determine blood pressure variation within and

between populations include age, gender, body mass index, and diet, principally sodium intake.

Cardiac output is highly dependent on blood volume, itself greatly influenced by the whole body sodium homeostasis. Peripheral vascular resistance is determined mainly at the level of the

arterioles and is affected by neural and hormonal factors. Normal vascular tone reflects the balance between humoral vasoconstricting influences (including angiotensin II, catecholamines,

and endothelin) and vasodilators (including kinins, prostaglandins, and NO). Resistance vessels also exhibit autoregulation, whereby increased blood flow induces vasoconstriction to

protect against tissue hyperperfusion. Other local factors such as pH and hypoxia, and the a- and b-adrenergic systems, which influence heart rate, cardiac contraction, and vascular tone,

may be important. 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:

Figure 11-13The critical roles of cardiac output and peripheral resistance in blood pressure regulation. NO, nitric oxide.

Figure 11-14Blood pressure regulation by the renin-angiotensin system and the central roles of sodium metabolism in specific causes of inherited and acquired forms of hypertension.

Components of the systemic renin-angiotensin system are shown in black. Genetic disorders that affect blood pressure by altering activity of this pathway are indicated in red; arrows

indicate sites in the pathway altered by mutation. Genes that are mutated in these disorders are indicated in parentheses. Acquired disorders that alter blood pressure through effects on this

pathway are indicated in blue. (From Lifton RP, et al: Molecular genetics of human blood pressure variation. Science 272:676, 1996.)

Figure 11-15Hypothetical scheme for the pathogenesis of essential hypertension, implicating genetic defects in renal excretion of sodium, functional regulation of vascular tone, and

structural regulation of vascular caliber. Environmental factors, especially increased salt intake, may potentiate the effects of genetic factors. The resultant increases in cardiac output and

peripheral resistance contribute to hypertension. ECF, extracellular fluid.

Figure 11-16Mutations altering blood pressure in humans. A diagram of a nephron, the filtering unit of the kidney, is shown. The molecular pathways mediating NaCl reabsorption in

individual renal cells in the thick ascending limb of the loop of Henle (TAL), distal convoluted tubule (DCT), and the cortical collecting tubule (CCT) are indicated, along with the pathway

of the renin-angiotensin system, the major regulator of renal salt reabsorption. Single gene defects that manifest as inherited diseases affecting these pathways are indicated, with

hypertensive disorders in red and hypotensive disorders in blue. Abbreviations: Al, angiotensin I; ACE, angiotensin converting enzyme; All, angiotensin II; MR, mineralocorticoid

receptor; GRA, glucocorticoid-remediable aldosteronism; PHA1, pseudohypoaldosteronism, type 1; AME, apparent mineralocorticoid excess; 11b-HSD2, 11b-hydroxysteroid

dehydrogenase-2; and DOC, deoxycorticosterone. (From Lifton RP, et al: Molecular mechanisms of human hypertension. Cell 104:545, 2001.)

Figure 11-17Vascular pathology in hypertension. A, Hyaline arteriolosclerosis. The arteriolar wall is hyalinized, and the lumen is markedly narrowed. B, Hyperplastic arteriolosclerosis

(onionskinning) causing luminal obliteration (arrow), with secondary ischemic changes, manifested by wrinkling of the glomerular capillary vessels at the upper left (periodic acid-Schiff

[PAS] stain). (Courtesy of Helmut Rennke, M.D., Brigham and Women's Hospital, Boston, MA.)

Figure 11-18True and false aneurysms. Center, Normal vessel. Left, True aneurysm. The wall bulges outward and may be attenuated but is intact. Right, False aneurysm. The wall is

ruptured, and there is a collection of blood (hematoma) that is bounded externally by adherent extravascular tissues.

Figure 11-19Abdominal aortic aneurysm. A, External view, gross photograph of a large aortic aneurysm that ruptured; the rupture site is indicated by the arrow. B, Opened view, with the

location of the rupture tract indicated by a probe. The wall of the aneurysm is exceedingly thin, and the lumen is filled by a large quantity of layered but largely unorganized thrombus.

Figure 11-20Aortic dissection. A, Gross photograph of opened aorta with proximal dissection, demonstrating a small, oblique intimal tear (demarcated by probe), allowing blood to enter

the media, creating an intramural hematoma (thin arrows). Note that the intimal tear has occurred in a region largely free from atherosclerotic plaque, and that propagation of the intramural

hematoma was arrested at a site more distally, where atherosclerosis begins (broad arrow). B, Histologic view of the dissection demonstrating an aortic intramural hematoma (asterisk).

Aortic elastic layers are black, and blood is red in this section, stained with the Movat stain.

Figure 11-21Medial degeneration. A, Cross-section of aortic media with marked elastin fragmentation and formation of areas devoid of elastin that resemble cystic spaces, from a patient

with Marfan syndrome. B, Normal media for comparison, showing the regular layered pattern of elastic tissue. In both A and B, the tissue section is stained to highlight elastin as black.

Figure 11-22Classification of dissection into types A and B. Type A (proximal) involves the ascending aorta, whereas type B (distal) does not. The serious complications predominantly

occur in the region from the aortic valve through the arch.

TABLE 11-4-- Classification of Vasculitis Based on Pathogenesis

(Not Available)

Data from Jennette JC, Falk RJ: Update on the pathobiology of vasculitis. In Schoen FJ, Gimbrone MA (eds); Cardiovascular Pathology: Clinicopathologic Correlations and

Pathogenetic Mechanisms. Baltimore, Williams & Wilkins, 1995, p 156.

chemical injury, such as irradiation, mechanical trauma, and toxins can also cause vascular damage.

Date: 2016-04-22; view: 598