The regulation of blood pressure and extracellular fluid volume

Introduction

Organ perfusion, and therefore function, is dependent on blood pressure (BP). The cardiovascular system does not govern BP by itself; equally important to the regulation of BP is the kidney’s control over the volume of the extracellular fluid (ECF).

• Recall that systemic blood pressure (SBP) is equal to the product of cardiac output (CO) and systemic vascular resistance (SVR).

  $\mathrm{SBP}\text{=}\mathrm{CO}\text{×}\mathrm{SVR}$

Note that this is analogous to Ohm’s law in electrical systems.

• The cardiovascular system affects BP by adjusting CO and SVR at the level of the heart and the arterioles, respectively.

• The kidney affects BP by adjusting the size of the ECF compartment, which affects the heart’s preload and CO.

• The cardiovascular and renal effectors of BP homeostasis act in concert, and the nervous system coordinates their efforts.

The kidneys control volume in the same way that they control the level of solutes in the bloodstream—by modifying the reabsorption of solutes and water filtered into the tubule.

System structure: Body fluid compartments

Recall that body fluid is divided into two spaces, extracellular and intracellular.

• ECF is divided into intravascular and interstitial compartments that are separated by capillary endothelium, which is freely permeable to water and small ions but not to proteins.

• Intracellular fluid (ICF) is the fluid contained inside all the cells of the body. The amount of solutes, predominantly ionic in nature, in the intracellular versus extracellular compartments determines the volume of fluid in each space.

Also remember from previous chapters that Na ⁺ (sodium) is the major cation of the ECF, and K ⁺ (potassium) is the major cation of the ICF ( Fig. 19.1 ).

• The Na ⁺ ,K ⁺ -adenosine triphosphatase (ATPase) pump that operates in all body tissues segregates Na ⁺ and K ⁺ to the outside and the inside of cells, respectively.

  • Na ⁺ is therefore primarily responsible for creating the osmotic pressure that holds water (and volume) in the extracellular space.

  • K ⁺ is primarily responsible for the osmotic pressure that holds water in the intracellular space. (See Ch. 1 for more discussion of osmotic pressure and fluid shifts.)

• Changes in the Na ⁺ concentration of the ECF alter the osmotic pressure of the ECF.

• If Na ⁺ is added to the ECF—for example, by eating a salty meal and absorbing salt into the blood from the intestines—the osmotic pressure of the ECF will increase, and water will move from the ICF into the ECF, thereby increasing the ECF volume.

The kidney makes use of this principle when it alters the volume of the ECF.

• By adjusting the amount of Na ⁺ reabsorbed from the nephron tubule, the kidney adjusts the osmotic gradient for water reabsorption from the tubule, and thereby adjusts the amount of water and volume reabsorbed from the tubule back into the bloodstream.

• The point here is not that water reabsorption always follows salt reabsorption in the kidney; in fact, in certain parts of the tubule, salt reabsorption without water is essential to kidney function.

• The kidney does not control ECF volume by hydrostatically pumping filtered water back into the bloodstream; instead, it does so by creating osmotic gradients with Na ⁺ , the major ECF cationic osmole ( Fig. 19.2 ).

  

System function: Blood pressure homeostasis

The kidneys maintain BP and perfusion pressure by increasing the ECF volume when perfusion pressure is low and decreasing ECF volume when perfusion pressure is high. Perfusion pressure refers to the local arterial BPs at particular organs, such as the brain or the kidneys, as opposed to the average systemic BP.

Fig. 19.3 breaks down renal and cardiovascular regulation of perfusion pressure into homeostatic elements.

Cardiovascular and renal regulation of perfusion pressure

The cardiovascular and renal regulation share similar sensors but use different effector mechanisms. As we shall see, renal and cardiovascular regulation are intimately connected.

In both systems, BP regulation begins with the baroreceptors, which sense changes in perfusion pressure. The term “baroreceptor reflex” is used to describe the feedback loop by which the nervous system responds to changes in perfusion pressure.

Cardiovascular regulation

Cardiovascular regulation is initiated by baroreceptors in the heart, lungs, and carotid arteries. On the basis of information it receives from the baroreceptors, the brain discharges impulses through the sympathetic nervous system and parasympathetic nervous system to control heart rate, heart contractility, and resistance of the blood vessels. The sympathetic outflow also impinges on the kidney to regulate proximal reabsorption, renin secretion, and renal vascular resistance.

• More sympathetic output raises BP and heart rate.

• More parasympathetic output slows the heart rate and lowers BP.

Renal regulation

Three main feedback loops constitute the renal regulation of BP.

• 1.

  BP changes within the renal microcirculation stimulate the juxtaglomerular apparatus (JGA) in the afferent arterioles, which in turn leads to changes in renin secretion which affect the renin-angiotensin-aldosterone (RAA) hormonal cascade.

  • a.

    Production of renin -> production of angiotensin II -> adrenal release of aldosterone.

  • b.

    Angiotensin II and aldosterone increase sodium (and thus) reabsorption from the renal tubules to increase intravascular volume, which increases systemic BP.

  • c.

    Angiotensin II also increases vascular resistance systemically, which increases systemic BP.

• 2.

  Atrial and ventricular receptors can sense stretch and alter the release of atrial natriuretic peptide (ANP), a 28-amino acid peptide stored in granules of the myocytes and brain natriuretic peptide (BNP). These peptides act as systemic vasodilators and reduce tubular salt/fluid reabsorption, which decreases BP.

• 3.

  Baroreceptors stimulate the secretion of antidiuretic hormone (ADH) in the setting of hypotension, which increases the reabsorption of water from the tubule and leads to increased systemic BP.

Fig. 19.4 provides an overview of the homeostatic responses to changes in perfusion pressure.

Sensors in regulation of perfusion pressure

BP changes throughout the day in accordance with numerous stimuli including:

• Stress

• Exertion

• Variations in dietary salt and water intake

• Fluid losses

• Many pathologic states, such as hemorrhage

Baroreceptors signal the brain in response to stretch in blood vessel walls.

• Baroreceptor cells “sense” stretch from the transmural pressure gradients across the vessel wall.

• When increased perfusion pressure distends the vessel wall, the baroreceptor increases its rate of firing.

• For example, the myocytes containing ANP and BNP stretch in response to a pressure gradient between the atrial cavity and the intrathoracic space (see Fast Fact Box 19.1 ).

Fast Fact Box 19.1

As mentioned in Chapter 10 , a perfusion pressure or driving pressure is the gradient of pressures between two locations within the circulation. The actual pressure at one site in the circulation contributes both to the transmural pressure across the vessel wall and the driving pressure forward through the circulation. Therefore the actual pressure at a site in the circulation where the peripheral or atrial mechanoreceptors exist contributes to a transmural distending pressure.

Baroreceptors exist in low-pressure and high-pressure areas of vasculature:

• Low-pressure baroreceptors:

  • Cardiac atria

  • Pulmonary vessels

• High-pressure baroreceptors:

  • Aortic arch

  • Carotid sinus

  • JGA in the afferent arterioles of the kidney (see Clinical Correlation Box 19.1 and Clinical Correlation Box 19.2 )

Clinical Correlate Box 19.1

In some pathologic conditions, the extracellular fluid (ECF) volume may be high (hypervolemia) while the perfusion pressures are low. In congestive heart failure, fluid pools in the veins and cardiac output falls owing to poor heart pumping ability. Because the homeostatic sensors respond to perfusion pressure, which will be low in the poor cardiac output state, they trigger changes in ECF volume. This added fluid collects in the high-capacitance veins and eventually leaks out into the interstitium from the peripheral capillary, causing swelling in the tissues. Clinically, this increase in volume is seen as pitting edema.

Clinical Correlation Box 19.2

Diuretics

Diuretics are drugs used to elevate urine volume and decrease extracellular fluid volume. They are most often used to treat hypertension or congestive heart failure. There are four kinds of diuretics: loop diuretics, thiazide-type diuretics, K ⁺ -sparing diuretics, and carbonic anhydrase inhibitors (see Figure below). Loop diuretics inhibit the Na/K/2Cl cotransporter in the loop of Henle, impeding salt reabsorption. Thiazide diuretics bind the Na/Cl cotransporter in the distal tubule, inhibiting salt reabsorption there. Loop and thiazide diuretics can promote K ⁺ wasting because they increase tubular flow to the K ⁺ secretion site in the collecting duct. Increased flow keeps the tubule [K ⁺ ] down and improves the gradient for K ⁺ secretion. K ⁺ -sparing diuretics inhibit salt reabsorption where salt reabsorption is coupled with K ⁺ secretion (i.e., they inhibit aldosterone), thereby preserving serum K ⁺ . Carbonic anhydrase inhibition in the proximal tubule cells inhibits bicarbonate reabsorption and thereby osmotically promotes diuresis. See Chapter 18 for additional details.

Remember that although ECF volume and perfusion pressure are related, they are not the same. Despite the fact that the kidney affects perfusion pressure by altering ECF volume, the kidney senses only arterial perfusion pressure to the kidney (see Clinical Correlation Box 19.3 ).

Clinical Correlation Box 19.3

In the case of renal artery stenosis, the juxtaglomerular apparatus senses a decrease in perfusion pressure at the afferent arteriole and increase the secretion of renin. The activation of the renin-angiotensin-aldosterone cascade leads to increase in volume, vasoconstriction, and finally hypertension.

Many texts use the term effective circulating volume (ECV) to address this concept of perfusion pressure in contrast with extracellular volume. The idea is that only some of the high fluid volume in the body is “effective”; that is, only some of the volume is actively perfusing the tissues while the rest remains pooled in the veins or sitting in the interstitium, effectively out of circulation. Alterations in ECV, not total ECF volume, drive the baroreceptor reflex.