Medical Physiology, 3rd Edition

Main Elements of Renal Function

The nephron forms an ultrafiltrate of the blood plasma and then selectively reabsorbs the tubule fluid or secretes solutes into it

As they do for capillaries elsewhere in the body, Starling forces (see pp. 467–468) govern the flow of fluid across the capillary walls in the glomerulus and result in net filtration. However, in the case of the glomerular capillaries, the filtrate flows not into the interstitium, but into Bowman's space, which is contiguous with the lumen of the proximal tubule.

The main function of renal tubules is to recover most of the fluid and solutes filtered at the glomerulus. If the fluid were not recovered, the kidney would excrete the volume of the entire blood plasma in less than half an hour. The retrieval of the largest fraction of glomerular filtrate occurs in the proximal tubule, which reabsorbs NaCl, NaHCO3, filtered nutrients (e.g., glucose and amino acids), divalent ions (e.g., Ca2+image, and image), and water. Finally, the proximal tubule secretes image and a variety of endogenous and exogenous solutes into the lumen.

The main function of the loop of Henle—tDLH, tALH, and TAL—is to participate in forming concentrated or dilute urine. The loop does this by pumping NaCl into the interstitium of the medulla without appreciable water flow, thus making the interstitium hypertonic. Downstream, the medullary collecting duct exploits this hypertonicity by either permitting or not permitting water to flow by osmosis into the hypertonic interstitium. In humans, only ~15% of the nephrons, the juxtamedullary nephrons, have long loops that descend to the tip of the papilla. Nevertheless, this subpopulation of nephrons (see Fig. 33-2) is extremely important for creating the osmotic gradients within the papilla that allow water movement out of the lumen of the entire population of medullary collecting ducts. As a result of this water movement, urine osmolality in the collecting ducts can far exceed that in the plasma.

TAL cells secrete the Tamm-Horsfall glycoprotein (THP), also known as uromodulin. imageN33-4 Normal subjects excrete 30 to 50 mg/day into the urine, which—along with albumin (<20 mg/day)—accounts for most of the protein normally present in urine. THP adheres to certain strains of Escherichia coli and may be part of the innate defense against urinary tract infections. This protein may also have a role in reducing aggregation of calcium crystals and thereby preventing formation of kidney stones. THP also constitutes the matrix of urinary casts. A cast is cylindrical debris in the urine that has taken the shape of the tubule lumen in which it was formed.

N33-4

Tamm-Horsfall Protein

Contributed by Walter Boron

The Tamm-Horsfall protein (THP)—also known as uromodulin—is the soluble cleavage product of an abundant glycosylphosphatidylinositol (GPI)–linked protein (see p. 13) on the apical membrane of the TAL cells. THP, normally the most abundant protein in the urine, may play a role in the defense against pathogenic bacteria in the genitourinary system.

Reference

Serafini-Cessi F, Malagolini N, Cavallone D. Tamm-Horsfall glycoprotein: Biology and clinical relevance. Am J Kidney Dis. 2003;42:658–676.

The classic distal tubule and the collecting-duct system perform the fine control of salt and water excretion. Although only small fractions of the glomerular filtrate reach these most distally located nephron sites, these tubule segments are where several hormones (e.g., aldosterone, arginine vasopressin) exert their main effects on electrolyte and water excretion.

The JGA is a region where each thick ascending limb contacts its glomerulus

Elements of the JGA play two important regulatory roles. First, if the amount of fluid and NaCl reaching a nephron's macula densa (see Fig. 33-3F) increases, the glomerular filtration rate (see p. 732) of that nephron falls. We discuss this phenomenon of tubuloglomerular feedback on pages 750–751.

The second regulatory mechanism comes into play during a decrease in the pressure of the renal artery feeding the various afferent arterioles. When the baroreceptor (see p. 841) in the afferent arteriole senses decreased stretch in the arteriole wall, it directs neighboring granular cells to increase their release of renin into the general circulation. We discuss the renin-angiotensin-aldosterone axis, which is important in the long-term control of systemic arterial blood pressure, on pages 841–842.

Sympathetic nerve fibers to the kidney regulate renal blood flow, glomerular filtration, and tubule reabsorption

The autonomic innervation to the kidneys is entirely sympathetic; the kidneys lack parasympathetic nerve fibers. The sympathetic supply to the kidneys originates from the celiac plexus (see Fig. 14-3) and generally follows the arterial vessels into the kidney. The varicosities of the sympathetic fibers release norepinephrine and dopamine into the loose connective tissue near the smooth-muscle cells of the vasculature (i.e., renal artery as well as afferent and efferent arterioles) and near the proximal tubules. Sympathetic stimulation to the kidneys has three major effects. First, the catecholamines cause vasoconstriction. Second, the catecholamines strongly enhance Na+ reabsorption by proximal-tubule cells. Third, as a result of the dense accumulation of sympathetic fibers near the granular cells of the JGA, increased sympathetic nerve activity dramatically stimulates renin secretion.

Renal nerves also include afferent (i.e., sensory) fibers. A few myelinated nerve fibers conduct baroreceptor and chemoreceptor impulses that originate in the kidney. Increased perfusion pressure stimulates renal baroreceptors in the interlobular arteries and afferent arterioles. Renal ischemia and abnormal ion composition of the interstitial fluid stimulate chemoreceptors located in the renal pelvis. These pelvic chemoreceptors probably respond to high extracellular levels of K+ and H+ and may elicit changes in capillary blood flow.

The kidneys, as endocrine organs, produce renin, 1,25-dihydroxyvitamin D, erythropoietin, prostaglandins, and bradykinin

Besides renin production by the JGA granular cells (see p. 841), the kidneys play several other endocrine roles. Proximal-tubule cells convert circulating 25-hydroxyvitamin D to the active metabolite, 1,25-dihydroxyvitamin D. This hormone controls Ca2+ and phosphorus metabolism by acting on the intestines, kidneys, and bone (see p. 1064), and is important for developing and maintaining bone structure.

Fibroblast-like cells in the interstitium of the cortex and outer medulla secrete erythropoietin (EPO) in response to a fall in the local tissue image (see pp. 431–433). EPO stimulates the development of red blood cells by action on hematopoietic stem cells in bone marrow. imageN18-2 In chronic renal failure, the deficiency of EPO leads to severe anemia that can be treated with recombinant EPO.

The kidney releases prostaglandins and several kinins, paracrine agents that control circulation within the kidney. These substances are generally vasodilators and may play a protective role when renal blood flow is compromised. Tubule cells also secrete angiotensin, bradykinin, cAMP, and ATP into the lumen, which can modulate downstream nephron function.