Physiology 5th Ed.


The kidneys receive about 25% of the cardiac output, which is among the highest of all the organ systems. Thus, in a person whose cardiac output is 5 L/min, renal blood flow (RBF) is 1.25 L/min or 1800 L/day! Such high rates of RBF are not surprising in light of the central role the kidneys play in maintaining the volume and composition of the body fluids.

Regulation of Renal Blood Flow

As with blood flow in any organ, RBF (Q) is directly proportional to the pressure gradient (ΔP) between the renal artery and the renal vein, and it is inversely proportional to the resistance (R) of the renal vasculature. (Recall from Chapter 4 that Q = ΔP/R. Recall, also, that resistance is provided mainly by the arterioles.) The kidneys are unusual, however, in that there are two sets of arterioles, the afferent and the efferent. The major mechanism for changing blood flow is by changing arteriolar resistance. In the kidney, this can be accomplished by changing afferent arteriolar resistance and/or efferent arteriolar resistance (Table 6-5).

Table 6–5 Renal Vasoconstrictors and Vasodilators



Sympathetic nerves (catecholamines)

Angiotensin II




Nitric oxide



Atrial natriuretic peptide

PG, Prostaglandin.

image Sympathetic nervous system and circulating catecholamines. Both afferent and efferent arterioles are innervated by sympathetic nerve fibers that produce vasoconstriction by activating α1 receptors.However, because there are far more α1 receptors on afferent arterioles, increased sympathetic nerve activity causes a decrease in both RBF and GFR. The effects of the sympathetic nervous system on renal vascular resistance can be appreciated by considering the responses to hemorrhage. Recall from Chapter 4 that blood loss and the resulting decrease in arterial pressure causes, via the baroreceptor mechanism, an increase in sympathetic outflow to the heart and blood vessels. When renal α1 receptors are activated by this increase in sympathetic activity, there is vasoconstriction of afferent arterioles that leads to a decrease in RBF and GFR. Thus, the cardiovascular system will attempt to raise arterial pressure even at the expense of blood flow to the kidneys.

image Angiotensin II. Angiotensin II is a potent vasoconstrictor of both afferent and efferent arterioles. The effect of angiotensin on RBF is clear: It constricts both sets of arterioles, increases resistance, and decreases blood flow. However, efferent arterioles are more sensitive to angiotensin II than afferent arterioles, and this difference in sensitivity has consequences for its effect on GFR (see the discussion on regulation of GFR). Briefly, low levels of angiotensin II produce an increase in GFR by constricting efferent arterioles, while high levels of angiotensin II produce a decrease in GFR by constricting both afferent and efferent arterioles. In hemorrhage, blood loss leads to decreased arterial pressure, which activates the renin-angiotensin-aldosterone system. The high level of angiotensin II, together with increased sympathetic nerve activity, constricts afferent and efferent arterioles and causes a decrease in RBF and GFR.

image Atrial natriuretic peptide (ANP). ANP and related substances such as brain natriuretic peptide (BNP) cause dilation of afferent arterioles and constriction of efferent arterioles. Because the dilatory effect of ANP on afferent arterioles is greater than the constrictor effect on efferent arterioles, there is an overall decrease in renal vascular resistance and resulting increase in RBF. Dilation of afferent arterioles and constriction of efferent arterioles both lead to increased GFR (see discussion on regulation of GFR).

image Prostaglandins. Several prostaglandins (e.g., prostaglandin E2 and prostaglandin I2) are produced locally in the kidneys and cause vasodilation of both afferent and efferent arterioles. The same stimuli that activate the sympathetic nervous system and increase angiotensin II levels in hemorrhage also activate local renal prostaglandin production. Although these actions may seem contradictory, the vasodilatory effects of prostaglandins are clearly protective for RBF. Thus, prostaglandins modulate the vasoconstriction produced by the sympathetic nervous system and angiotensin II. Unopposed, this vasoconstriction can cause a profound reduction in RBF, resulting in renal failure. Nonsteroidal antiinflammatory drugs (NSAIDs) inhibit synthesis of prostaglandins and, therefore, interfere with the protective effects of prostaglandins on renal function following a hemorrhage.

image Dopamine. Dopamine, a precursor of norepinephrine, has selective actions on arterioles in several vascular beds. At low levels, dopamine dilates cerebral, cardiac, splanchnic, and renal arterioles, and itconstricts skeletal muscle and cutaneous arterioles. Thus, a low dosage of dopamine can be administered in the treatment of hemorrhage because of its protective (vasodilatory) effect on blood flow in several critical organs including the kidneys.

Autoregulation of Renal Blood Flow

RBF is autoregulated over a wide range of mean arterial pressures (Pa) (Fig. 6-6). Renal arterial pressure can vary from 80 to 200 mm Hg, yet RBF will be kept constant. Only when renal arterial pressure decreases to less than 80 mm Hg does RBF also decrease. The only way to maintain this constancy of blood flow in the face of changing arterial pressure is by varying the resistance of the arterioles. Thus, as renal arterial pressure increases or decreases, renal resistance must increase or decrease proportionately (recall that Q = ΔP/R).


Figure 6–6 Autoregulation of renal blood flow and glomerular filtration rate. Pa, Renal artery pressure.

For renal autoregulation, it is believed that resistance is controlled primarily at the level of the afferent arteriole, rather than the efferent arteriole. The mechanism of autoregulation is not completely understood. Clearly, the autonomic nervous system is not involved because a denervated (e.g., transplanted) kidney autoregulates as well as an intact kidney. The major theories explaining renal autoregulation are a myogenic mechanism and tubuloglomerular feedback.

image Myogenic hypothesis. The myogenic hypothesis states that increased arterial pressure stretches the blood vessels, which causes reflex contraction of smooth muscle in the blood vessel walls and consequently increased resistance to blood flow (see Chapter 4). The mechanism of stretch-induced contraction involves the opening of stretch-activated calcium (Ca2+channels in the smooth muscle cell membranes. When these channels are open, more Ca2+enters vascular smooth muscle cells, leading to more tension in the blood vessel wall. The myogenic hypothesis explains autoregulation of RBF as follows: Increases in renal arterial pressure stretch the walls of the afferent arterioles, which respond by contracting. Afferent arteriolar contraction leads to increased afferent arteriolar resistance. The increase in resistance then balances the increase in arterial pressure, and RBF is kept constant.

image Tubuloglomerular feedback. Tubuloglomerular feedback is also a mechanism for autoregulation (Fig. 6-7), explained as follows: When renal arterial pressure increases, both RBF and GFR increase. The increase in GFR results in increased delivery of solute and water to the macula densa region of the early distal tubule, which senses some component of the increased delivered load. The macula densa, which is a part of the juxtaglomerular apparatus,responds to the increased delivered load by secreting a vasoactive substance that constricts afferent arterioles via a paracrine mechanism. Local vasoconstriction of afferent arterioles then reduces RBF and GFR back to normal; that is, there is autoregulation.


Figure 6–7 Mechanism of tubuloglomerular feedback. GFR, Glomerular filtration rate; RBF, renal blood flow.

There are two major unanswered questions concerning the mechanism of tubuloglomerular feedback: (1) What component of tubular fluid is sensed at the macula densa? The major candidates are luminal Na+and Cl. (2) What vasoactive substance is secreted by the juxtaglomerular apparatus to act locally on afferent arterioles? Here, the candidates are adenosine, ATP, and thromboxane.

Measurement of Renal Plasma Flow and Renal Blood Flow

Renal plasma flow (RPF) can be estimated from the clearance of an organic acid para-aminohippuric acid (PAH). Renal blood flow (RBF) is calculated from the RPF and the hematocrit.

Measuring True Renal Plasma Flow—Fick Principle

The Fick principle states that the amount of a substance entering an organ equals the amount of the substance leaving the organ (assuming that the substance is that the amount of degraded by the organ). Applied to the kidney, the Fick principle states that the amount of a substance entering the kidney via the renal artery equals the amount of the substance leaving the kidney via the renal vein plus the amount excreted in the urine (Fig. 6-8).


Figure 6–8 Measurement of renal plasma flow by the Fick principle. PAH, Para-aminohippuric acid; [RA], concentration in renal artery; RPF, renal plasma flow; [RV], concentration in renal vein; [U], concentration in urine.

PAH is the substance used to measure RPF with the Fick principle, and the derivation is as follows:






Solving for RPF,




= Renal plasma flow


= [PAH] in urine


= Urine flow rate


= [PAH] in renal artery


= [PAH] in renal vein

PAH has the following characteristics that make it the ideal substance for measuring RPF: (1) PAH is neither metabolized nor synthesized by the kidney. (2) PAH does not alter RPF. (3) The kidneys extract (remove) most of the PAH from renal arterial blood by a combination of filtration and secretion. As a result, almost all of the PAH entering the kidney via the renal artery is excreted in urine, leaving little in the renal vein. Because the renal vein concentration of PAH is nearly zero, the denominator of the previous equation ([RA]PAH − [RV]PAH) is large and, therefore, can be measured accurately. To elaborate this point, compare a substance such as glucose, which is notremoved from renal arterial blood at all. Renal vein blood will have the same glucose concentration as renal artery blood, and the denominator of the equation will be zero, which is not mathematically permissible. Clearly, glucose cannot be used to measure RPF. (4) No organ, other than the kidney, extracts PAH, so the PAH concentration in the renal artery is equal to the PAH concentration in any peripheral vein. Peripheral venous blood can be sampled easily, whereas renal arterial blood cannot.

Measuring Effective Renal Plasma Flow—Clearance of Para-Aminohippuric Acid

The previous section explains the measurement of true renal plasma flow, which involves infusion of PAH, sampling urine, and sampling blood from the renal artery and renal vein. In humans, it is difficult, if not impossible, to obtain blood samples from the renal blood vessels. However, based on the properties of PAH, certain simplifications can be applied to measure effective RPF, which approximates true RPF to within 10%.

The first simplification is that [RV]PAH is assumed to be zero. This is a reasonable assumption because most of the PAH entering the kidney via the renal artery is excreted in the urine by the combined processes of filtration and secretion. The second simplification is that [RA]PAH equals the PAH concentration in any peripheral vein, which can be easily sampled. With these modifications, the equation for RPF becomes



Effective RPF

= Effective renal plasma flow (mL/min)


= Urine concentration of PAH (mg/mL)


= Urine flow rate (mL/min)


= Plasma concentration of PAH (mg/mL)


= Clearance of PAH (mL/min)

Thus, in the simplified form, effective RPF equals the clearance of PAH. Effective RPF underestimates true RPF by approximately 10% because [RV]PAH is not zero—it is nearly zero. [RV]PAH is not zero because a small fraction of the RPF serves kidney tissue that is not involved in filtration and secretion of PAH (e.g., renal adipose tissue, renal capsule). PAH will not be extracted from this portion of the RPF, and the PAH contained in that blood is returned to the renal vein.

Measuring Renal Blood Flow

RBF is calculated from RPF and the hematocrit (Hct). The formula used to calculate RBF is as follows:




= Renal blood flow (mL/min)


= Renal plasma flow (mL/min)


= Hematocrit

Thus, RBF is the RPF divided by 1 minus the hematocrit, where hematocrit is the fraction of blood volume that is occupied by red blood cells, and 1 − hematocrit is the fraction of blood volume that is occupied by plasma.

SAMPLE PROBLEM. A man with a urine flow rate of 1 mL/min has a plasma concentration of PAH of 1 mg%, a urine concentration of PAH of 600 mg%, and a hematocrit of 0.45. What is his RBF?

SOLUTION. Because values are not given for renal artery and renal vein concentrations of PAH, true RPF (and true RBF) cannot be calculated. However, effective RPF can be calculated from the clearance of PAH. Effective RBF can then be calculated by using the hematocrit. Remember, mg% means mg/100 mL.