Chapter 036. Edema (Part 2) pptx

Edema Part 2 Reduction of Effective Arterial Volume In many forms of edema, the effective arterial blood volume, a parameter that represents the filling of the arterial tree, is reduce

Chapter 036 Edema

(Part 2)

Reduction of Effective Arterial Volume

In many forms of edema, the effective arterial blood volume, a parameter that represents the filling of the arterial tree, is reduced Underfilling of the arterial tree may be caused by a reduction of cardiac output and/or systemic vascular resistance As a consequence of underfilling, a series of physiologic responses designed to restore the effective arterial volume to normal are set into motion A key element of these responses is the retention of salt and, therefore, of water, ultimately leading to edema

Renal Factors and the Renin-Angiotensin-Aldosterone (RAA) System

(See also Chap 336) In the final analysis, renal retention of Na+ is central

to the development of generalized edema The diminished renal blood flow

characteristic of states in which the effective arterial blood volume is reduced is translated by the renal juxtaglomerular cells (specialized myoepithelial cells surrounding the afferent arteriole) into a signal for increased renin release (Chap 336) Renin is an enzyme with a molecular mass of about 40,000 Da that acts on its substrate, angiotensinogen, an α2-globulin synthesized by the liver, to release angiotensin I, a decapeptide, which is broken down to angiotensin II (AII), an octapeptide AII has generalized vasoconstrictor properties; it is especially active

on the efferent arterioles This efferent arteriolar constriction reduces the hydrostatic pressure in the peritubular capillaries, while the increased filtration fraction raises the colloid osmotic pressure in these vessels, thereby enhancing salt and water reabsorption in the proximal tubule as well as in the ascending limb of the loop of Henle

The RAA system has long been recognized as a hormonal system; however,

it also operates locally Intrarenally produced AII contributes to glomerular efferent arteriolar constriction, and this "tubuloglomerular feedback" causes salt and water retention These renal effects of AII are mediated by activation of AII type 1 receptors, which can be blocked by specific antagonists [angiotensin receptor blockers (ARBs)]

The mechanisms responsible for the increased release of renin when renal blood flow is reduced include: (1) a baroreceptor response in which reduced renal perfusion results in incomplete filling of the renal arterioles and diminished stretch

of the juxtaglomerular cells, a signal that increases the elaboration and/or release

of renin; (2) reduced glomerular filtration, which lowers the NaCl load reaching the distal renal tubules and the macula densa, cells in the distal convoluted tubules that act as chemoreceptors and that signal the neighboring juxtaglomerular cells to secrete renin; and (3) activation of the β-adrenergic receptors in the juxtaglomerular cells by the sympathetic nervous system and by circulating catecholamines, which also stimulates renin release These three mechanisms generally act in concert to enhance Na+ retention and, thereby, contribute to the formation of edema

AII that enters the systemic circulation stimulates the production of aldosterone by the zona glomerulosa of the adrenal cortex Aldosterone, in turn, enhances Na+ reabsorption (and K+ excretion) by the collecting tubule In patients with heart failure, not only is aldosterone secretion elevated but the biologic half-life of aldosterone is prolonged, which increases further the plasma level of the hormone A depression of hepatic blood flow, especially during exercise, is responsible for reduced hepatic catabolism of aldosterone The activation of the RAA system is most striking in the early phase of acute, severe heart failure and is less intense in patients with chronic, stable, compensated heart failure

Increased quantities of aldosterone are secreted in heart failure and in other edematous states, and blockade of the action of aldosterone by spironolactone (an aldosterone antagonist) or amiloride (a blocker of epithelial Na+ channels) often

induces a moderate diuresis in edematous states Yet, persistently augmented levels of aldosterone (or other mineralocorticoids) alone do not always promote accumulation of edema, as witnessed by the lack of striking fluid retention in most instances of primary aldosteronism (Chap 336) Furthermore, although normal individuals retain some NaCl and water with the administration of potent mineralocorticoids, such as deoxycorticosterone acetate or fludrocortisone, this accumulation is self-limiting, despite continued exposure to the steroid, a

phenomenon known as mineralocorticoid escape The failure of normal

individuals who receive large doses of mineralocorticoids to accumulate large quantities of extracellular fluid and to develop edema is probably a consequence of

an increase in glomerular filtration rate (pressure natriuresis) and the action of natriuretic substance(s) (see below) The continued secretion of aldosterone may

be more important in the accumulation of fluid in edematous states because patients with edema secondary to heart failure, nephrotic syndrome, and hepatic cirrhosis are generally unable to repair the deficit in effective arterial blood volume As a consequence, they do not develop pressure natriuresis

Arginine Vasopressin (AVP)

(See also Chap 334) The secretion of AVP occurs in response to increased intracellular osmolar concentration, and by stimulating V2 receptors, AVP increases the reabsorption of free water in the renal distal tubule and collecting duct, thereby increasing total-body water Circulating AVP is elevated in many

patients with heart failure secondary to a nonosmotic stimulus associated with decreased effective arterial volume Such patients fail to show the normal reduction of AVP with a reduction of osmolality, contributing to edema formation and hyponatremia