Effective Arterial Blood Volume

a Results from an experiment performed on a 10-kg dog. Note that in response to an increase in GFR (produced by infusing a drug that dilated afferent arterioles), tubular reabsorption of Na+ increased, so that only a modest increase in Na+ excretion occurred. If there had been no glomerulotubular balance and if tubular Na+ reabsorption had stayed at 5.95 mEq/min, the kidneys would have excreted 2.05 mEq/min in period 2. If we assume that the ECF volume in the dog is 2 L (20% of body weight) and if plasma [Na+] is 140 mEq/L, an excretion rate of 2.05 mEq/min would result in excretion of the entire ECF Na+ (280 mEq) in a little more than 2 hours. The dog would have been dead long before this could happen, which underscores the importance of glomerulotubular balance.

1) A decrease in pressure in the afferent arteriole, with the granular cells being sensitive to stretch and function as an intrarenal baroreceptor

2) Stimulation of sympathetic nerve fibers to the kidneys via (^-adrenergic receptors on the granular cells

3) A decrease in fluid delivery to the macula densa region of the nephron, resulting, for example, from a decrease in GFR

All three of these pathways are activated and reinforce each other when there is a decrease in the effective arterial blood volume—for example, following hemorrhage, tran-sudation of fluid out of the vascular system, diarrhea, severe sweating, or a low salt intake. Conversely, an increase in the effective arterial blood volume inhibits renin release. Long-term stimulation causes vascular smooth muscle cells in the afferent arteriole to differentiate into granular cells and leads to further increases in renin supply. Renin in the blood plasma acts on a plasma a2-globulin produced by the liver, called angiotensinogen (or renin substrate) and splits off the decapeptide angiotensin I (Fig. 24.9). Angiotensin I is converted to the octapeptide angiotensin II as the blood courses through the lungs. This reaction is catalyzed by the angiotensin-converting enzyme (ACE), which is present on the surface of endothelial cells. All the components of this system (renin, angiotensinogen, angiotensin-converting enzyme) are present in some organs (e.g., the kidneys and brain), so that angiotensin II may also be formed and act locally.

The renin-angiotensin-aldosterone system (RAAS) is a salt-conserving system. Angiotensin II has several actions related to Na+ and water balance:

1) It stimulates the production and secretion of the aldosterone from the zona glomerulosa of the adrenal cortex (see Chapter 36). This mineralocorticoid hormone then acts on the distal nephron to increase Na+ reabsorption.

2) Angiotensin II directly stimulates tubular Na+ reabsorption.

3) Angiotensin stimulates thirst and the release of AVP by the posterior pituitary.

Angiotensin II is also a potent vasoconstrictor of both resistance and capacitance vessels,- increased plasma levels following hemorrhage, for example, help sustain blood pressure. Inhibiting angiotensin II production by giving an ACE inhibitor lowers blood pressure and is used in the treatment of hypertension.

The RAAS plays an important role in the day-to-day control of Na+ excretion. It favors Na+ conservation by the kidneys when there is a Na+ or volume deficit in the body. When there is an excess of Na+ or volume, diminished RAAS activity permits enhanced Na+ excretion. In the absence of aldosterone (e.g., in an adrenalectomized individual) or in a person with adrenal cortical insufficiency—Addison's disease—excessive amounts of Na+ are lost in the urine. Percentage reabsorption of Na+ may decrease from a normal value of about 99.6% to a value of 98%. This change (1.6% of the filtered Na+ load) may not seem like much, but if the kidneys filter 25,200 mEq/day (see Table 24.4) and excrete an extra 0.016 X 25,200 = 403 mEq/day, this is the amount of Na+ in almost 3 L of ECF (assuming a [Na+] of 140 mEq/L). Such a loss of Na+ would lead to a decrease in plasma and blood volume, circulatory collapse, and even death.

When there is an extra need for Na+, people and many animals display a sodium appetite, an urge for salt intake, which can be viewed as a brain mechanism, much like thirst, that helps compensate for a deficit. Patients with Addison's disease often show a well-developed sodium appetite, which helps keep them alive.

Large doses of a potent mineralocorticoid will cause a person to retain about 200 to 300 mEq Na+ (equivalent to about 1.4 to 2 L of ECF), and the person will "escape" from the salt-retaining action of the steroid. Retention of this amount of fluid is not sufficient to produce obvious edema. The fact that the person will not continue to accumulate Na+ and water is due to the existence of numerous factors that are called into play when ECF volume is expanded, these factors promote renal Na+ excretion and overpower the salt-retaining action of aldosterone. This phenomenon is called mineralocorticoid escape.

Intrarenal Physical Forces (Peritubular Capillary Starling Forces). An increase in the hydrostatic pressure or a decrease in the colloid osmotic pressure in peritubular capillaries (the so-called "physical" or Starling forces) results in reduced fluid uptake by the capillaries. In turn, an accumulation of the reabsorbed fluid in the kidney interstitial spaces results. The increased interstitial pressure causes a widening of the tight junctions between proximal tubule cells, and the epithelium becomes even more leaky than normal. The result is increased back-leak of salt and water into the tubule lumen and an overall reduction in net reabsorption. These changes occur, for example, if a large volume of isotonic saline is infused intravenously. They also occur if the filtration fraction (GFR/RPF) is lowered from the dilation of efferent arterioles, for example. In this case, the protein concentration (or colloid osmotic pressure) in efferent arteriolar blood and peritubular capillary blood is lower than normal because a smaller proportion of the plasma is filtered in the glomeruli. Also, with upstream vasodilation of efferent arterioles, hydrostatic pressure in the

Effective Arterial Blood Volume
Angiotensin II
Effective Arterial Blood Volume

Components of the renin-angiotensin-aldos-terone system. This system is activated by a decrease in the effective arterial blood volume (e.g., following hemorrhage) and results in compensatory changes that help restore arterial blood pressure and blood volume to normal.

Components of the renin-angiotensin-aldos-terone system. This system is activated by a decrease in the effective arterial blood volume (e.g., following hemorrhage) and results in compensatory changes that help restore arterial blood pressure and blood volume to normal.

peritubular capillaries is increased, leading to a pressure na-triuresis and pressure diuresis. The term natriuresis means an increase in Na+ excretion.

Natriuretic Hormones and Factors. Atrial natriuretic peptide (ANP) is a 28 amino acid polypeptide synthesized and stored in myocytes of the cardiac atria (Fig. 24.10). It is released upon stretch of the atria—for example, following volume expansion. This hormone has several actions that increase Na+ excretion. ANP acts on the kidneys to increase glomerular blood flow and filtration rate and inhibits Na+ reabsorption by the inner medullary collecting ducts. The second messenger for ANP in the collecting duct is cGMP. ANP directly inhibits aldosterone secretion by the adrenal cortex, it also indirectly inhibits aldosterone secretion by diminishing renal renin release. ANP is a vasodilator and, therefore, lowers blood pressure. Some evidence suggests that ANP inhibits AVP secretion. The actions of ANP are, in many respects, just the opposite of those of the RAAS,- ANP promotes salt and water loss by the kidneys and lowers blood pressure.

Several other natriuretic hormones and factors have been described. Urodilatin (kidney natriuretic peptide) is a 32-amino acid polypeptide derived from the same prohormone as ANP. It is synthesized primarily by intercalated cells in the cortical collecting duct and secreted into the tubule lu

Natriuretic Hormone

Atrial natriuretic peptide and its actions.

ANP release from the cardiac atria is stimulated by blood volume expansion, which stretches the atria. ANP produces effects that bring blood volume back toward normal, such as increased Na+ excretion.

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  • aki
    What would happen to Na balance if glomerulotubular balance did not exist?
    2 years ago

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