The morphologically distinct region of the thick ascending limb known as the cells of the macula densa pass through the angle formed by the afferent and efferent arterioles of the same nephron. These cells make contact with the extraglomerular mesangial cells and the granular cells of the afferent arterioles. The granular cells of the afferent arterioles contain smooth muscle myofilaments and are responsible for the production, storage, and release of renin in response to signals associated with decreased effective circulating volume and reduced renal perfusion. Renin plays a crucial role in the proteolytic generation of angiotensin II and ultimately in the secretion of aldosterone. The juxtaglomerular apparatus is a component of the tubuloglomerular feedback mechanism involved in the autoregulation of renal blood flow and glomerular filtration rate.

The nerve supply to the kidneys consists of sympathetic nerve fibers originating in the celiac plexus. Adrenergic fibers release norepinephrine and are located adjacent to the smooth muscle cells of the major branches of the renal artery as well as the afferent and efferent arterioles. Sympathetic nerves also innervate the renin-producing granular cells of the afferent arterioles. Increased sympathetic activity stimulates renin secretion. In addition to the blood vessels, sympathetic nerves innervate various segments of the nephron, including the proximal tubule, loop of Henle, distal tubule, and collecting duct. Activation of these nerves enhances sodium reabsorption in these nephron segments.

The final amount of a substance excreted in urine is determined by the coordinated actions of the nephron's various segments. This process involves glomerular filtration, tubular reabsorption, and in some cases, tubular secretion. The principle of renal clearance focuses on the excretory function of the kidneys and considers only the rate at which a substance is excreted into urine, not its rate of return to the systemic circulation in the renal vein. The urinary excretion rate of a substance is proportional to its plasma concentration, and the removal rate of a substance from plasma is referred to as its clearance. To equate the urinary excretion rate of a substance to its renal arterial plasma concentration, it is necessary to determine the rate at which it is removed from plasma by filtration and/or secretion.
The cells of the macula densa represent a morphologically distinct region of the thick ascending limb. This region passes through the angle formed by the afferent and efferent arterioles of the same nephron. The cells of the macula densa contact the extraglomerular mesangial cells and the granular cells of the afferent arterioles. The granular cells of the afferent arterioles contain smooth muscle myofilaments and—importantly—manufacture, store, and release renin in response to signals associated with decreased effective • Fig. 33.11 Overview of the major proteins that form the slit diaphragm. Nephrins (red) from opposite foot processes interdigitate in the center of the slit. In the slit, nephrin interacts with NEPH1 and NEPH2 (blue), FAT1 and FAT2 (green), and P-cadherin. The intracellular domains of nephrin, NEPH1, and NEPH2 interact with podocin and CD2-AP, which connect these slit diaphragm proteins with ZO-1, α-actinin 4, and actin. (Modified from Tryggvason K et al. N Engl J Med 2006;354:1387.) circulating volume and reduced renal perfusion. Renin is involved in proteolytic generation of angiotensin II and ultimately in secretion of aldosterone (see ). The juxtaglomerular apparatus is one component of the tubuloglomerular feedback mechanism involved in autoregulation of RBF and GFR.
Innervation of the Kidneys
Renal nerves regulate RBF, GFR, and salt and water reabsorption by the nephron. The nerve supply to the kidneys consists of sympathetic nerve fibers that originate in the celiac plexus. There is no corresponding parasympathetic innervation. Adrenergic fibers innervating the kidneys release norepinephrine and lie adjacent to the smooth muscle cells of the major branches of the renal artery (interlobar, arcuate, and interlobular arteries) as well as the afferent and efferent arterioles. In addition, sympathetic nerves innervate the renin-producing granular cells of the afferent arterioles. Renin secretion is stimulated by increased sympathetic activity. Nerve fibers also innervate the proximal tubule, loop of Henle, distal tubule, and collecting duct; activation of these nerves enhances Na+ reabsorption by these nephron segments.
Assessment of Renal Function
The coordinated actions of the nephron’s various segments determine the final amount of a substance that appears in urine. This represents three general processes (1) glomerular
CHAPTER 33 Elements of Renal Function
This relationship permits quantification of the amount of substance x excreted in urine versus the amount returned to the systemic circulation in renal venous blood. Thus for any substance that is neither synthesized nor metabolized, the amount that enters the kidneys is equal to the amount that leaves the kidneys in urine plus the amount that leaves the kidneys in renal venous blood.
The principle of renal clearance emphasizes the excretory function of the kidneys; it considers only the rate at which a substance is excreted into urine and not its rate of return to the systemic circulation in the renal vein. Therefore in terms of mass balance (
Eq. 33.1 ) the urinary excretion rate of substance x (Ux × V̇ ) is proportional to the plasma concentration of substance x (
Equation 33.2
To equate the urinary excretion rate of substance x to • Fig. 33.12 Mass balance relationships for the kidney. See text for definition of symbols.
its renal arterial plasma concentration, it is necessary to determine the rate at which it is removed from plasma by filtration, (2) reabsorption of the substance from tubular the kidneys. This removal rate is the clearance (Cx): fluid back into blood, and (3) (in some cases) secretion of