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