Renal Physiology: Chapter Goals After studying this chapter, students should be able to . . . 1. describe the different regions of the nephron tubules and explain the anatomic relationship between the tubules and the gross structure of the kidney. 2. describe the structural and functional relationships between the nephron tubules and their associated blood vessels. 3. describe the composition of glomerular ultrafiltrate and explain how it is produced. 4. explain how the proximal convoluted tubule reabsorbs salt and water. 5. describe active transport and osmosis in the loop of Henle and explain how these processes produce a countercurrent multiplier system. 6. explain how the vasa recta function in countercurrent exchange. 7. describe the role of antidiuretic hormone (ADH) in regulating the final urine volume. 8. describe the mechanisms of glucose reabsorption and explain the meanings of the terms transport maximum and renal plasma threshold.

Renal Physiology: Chapter Goals 9. define the renal plasma clearance, and explain why the clearance of inulin is equal to the glomerular filtration rate. 10. explain how the clearance of different molecules is determined and how the processes of reabsorption and secretion affect the clearance measurement.. 11. explain the mechanism of Na+ reabsorption in the distal tubule and why this reabsorption occurs together with the secretion of K+. 12. describe the effects of aldosterone on the distal convoluted tubule and how aldosterone secretion is regulated. 13. explain how activation of the renin-angiotensin system results in the stimulation of aldosterone secretion. 14. describe the interactions between plasma K+ and H+ concentrations and explain how this affects the tubular secretion of these ions. 15. describe the role of the kidneys in the regulation of acid-base balance. 16. describe the different mechanisms by which substances can act as diuretics and explain why some cause excessive loss of K+.

Renal Physiology Functional Relationships Urinary System Anatomy Nephron

Functional Relationships

Urinary System Anatomy Kidneys Nephrons

14.1a

14-1b

14-3

Juxtamedullary Nephron Cortical Nephron 14-5

14-8

Nephron Function Filtration Tubular Secretion Selective Reabsorption

14-6

14-7

Filtration Analysis of Glomerular Capillary Dynamics Blood Pressure =55.0 mm Hg O (vs 35 normally) Plasma Coll O.P. =30.0 mm Hg I BC Hydrostatic P. =15.0 mm Hg I 10.0 mm Hg O = Filtration Pressure Table 14-1

Regulation of Filtration Pressure 14-10

Regulation of Filtration Pressure 14-11

Filtration (cont’d) Regulation of Filtration Pressure - via juxtaglomerular apparatus

14-12

Autoregulation of High Filtration Pressure 14-13

Tubular Secretion/Selective Reabsorption Tubular Maximum Urine = (Filtration - reabsorption) + Secretion

14-21

Fox 17.20

Regulation of Blood Composition 1. Electrolytes and Solutes a. Na+ high in blood; low in cells b. K+ high in cells; low in blood c. Aldosterone (from adrenal gland) Ž  Na+ uptake and  K+ uptake (into blood)

Saving Sodium 14-18

14-19

Losing Sodium 14-20

14.24

14-25

14-26a

14-26b

14-26c

14-26d

Regulation of Blood Composition 2. pH: too low - H+Ž to tubule; too high - H + Ž to blood a. Definition - pH = -log [H+] b. How buffers work - e.g. tie up H+ from a strong acid with the salt of a weak acid, which forms a weak acid.

Regulation of Blood Composition

Regulation of Blood Composition

Regulation of Blood Composition 15-10

Regulation of Blood Composition 15-11

Regulation of Blood Composition 3. Water 80% reabsorbed by elevated osmotic pressure of blood in capillaries of efferent renal arteriole following filtration by the glomerulus Countercurrent Mechanism - salvages water from glomerular filtrate, so produces a concentrated urine

Water Reabsorption 17-22

Countercurrent Mechanism i. Produce Na+ concentration gradient via active transport in ascending branch of the Loop of Henle. ii. Maintain Na+ concentration gradient against tendency to diffuse. iii. Use Na+ concentration gradient to salvage water

Countercurrent Mechanism 14-27

14-28a

14-28b

14-28c

14-28d

14-28e

14-28f

14-28g

14-29

14-31a

14-31b

Chapter Summary Structure and Function of the Kidneys I. The kidney is divided into an outer cortex and inner medulla. A. The medulla is composed of renal pyramids, separated by renal columns. B. The renal pyramids empty urine into the calyces that drain into the renal pelvis. From there urine flows into the ureter and is transported to the bladder to be stored. II. Each kidney contains more than a million microscopic functional units called nephrons. Nephrons consist of vascular and tubular components. A. Filtration occurs in the glomerulus, which receives blood from an afferent arteriole. B. Glomerular blood is drained by an efferent arteriole, which delivers blood to peritubular capillaries that surround the nephron tubules. C. The glomerular (Bowman’s) capsule and the proximal and distal convoluted tubules are located in the cortex. D. The loop of Henle is located in the medulla. E. Filtrate from the distal convoluted tubule is drained into collecting ducts, which plunge through the medulla to empty urine into the calyces.

Chapter Summary Glomerular Filtration I. A filtrate derived from plasma in the glomerulus must pass though a basement membrane of the glomerular capillaries and through slits in the processes of the podocytes, the cells that compose the inner layer of the glomerular (Bowman’s) capsule. A. The glomerular ultrafiltrate, formed under the force of blood pressure, has a low protein concentration. B. The glomerular filtration rate (GFR) is the volume of filtrate produced by both kidneys each minute. It ranges from 115 to 125 ml/min. II. The GFR can be regulated by constriction or dilation of the afferent arterioles. A. Sympathetic innervation causes constriction of the afferent arterioles. B. Intrinsic mechanisms help to autoregulate the rate of renal blood flow and the GFR.

Chapter Summary Reabsorption of Salt and Water I. Approximately 65% of the filtered salt and water is reabsorbed across the proximal convoluted tubules. A. Sodium is actively transported, chloride follows passively by electrical attraction, and water follows the salt out of the proximal tubule. B. Salt transport in the proximal tubules is not under hormonal regulation. II. The reabsorption of most of the remaining water occurs as a result of the action of the countercurrent multiplier system. A. Sodium is actively extruded from the ascending limb, followed passively by chloride. B. Since the ascending limb is impermeable to water, the remaining filtrate becomes hypotonic. C. Because of this salt transport and because of countercurrent exchange in the vasa recta, the tissue fluid of the medulla becomes hypertonic. D. The hypertonicity of the medulla is multiplied by a positive feedback mechanism involving the descending limb, which is passively permeable to water and perhaps to salt.

Chapter Summary Reabsorption of Salt and Water III. The collecting duct is permeable to water but not to salt. A. As the collecting ducts pass through the hypertonic renal medulla, water leaves by osmosis and is carried away in surrounding capillaries. B. The permeability of the collecting ducts to water is stimulated by antidiuretic hormone (ADH).

Chapter Summary Renal Plasma Clearance I. Inulin is filtered but neither reabsorbed nor secreted. Its clearance is thus equal to the glomerular filtration rate. II. Some of the filtered urea is reabsorbed. Its clearance is therefore less than the glomerular filtration rate. III. Since almost all the PAH in blood going through the kidneys is cleared by filtration and secretion, the PAH clearance is a measure of the total renal blood flow. IV. Normally all of the filtered glucose is reabsorbed. Glycosuria occurs when the transport carriers for glucose become saturated as a result of hyperglycemia.

Chapter Summary Renal Control of Electrolyte and Acid-Base Balance I. Aldosterone stimulates sodium reabsorption and potassium secretion in the distal convoluted tubule. II. Aldosterone secretion is stimulated directly by a rise in blood potassium and indirectly by a fall in blood sodium. A. Decreased blood flow through the kidneys stimulates the secretion of the enzyme renin from the juxtaglomerular apparatus. B. Renin catalyzes the formation of angiotensin I, which is then converted to angiotensin II. C. Angiotensin II stimulates the adrenal cortex to secrete aldosterone. III. Aldosterone stimulates the secretion of H+, as well as potassium, into the filtrate in exchange for sodium.

Chapter Summary Renal Control of Electrolyte and Acid-Base Balance IV. The nephrons filter bicarbonate and reabsorb the amount required to maintain acid- base balance. Reabsorption of bicarbonate, however, is indirect. A. Filtered bicarbonate combines with H+ to form carbonic acid in the filtrate. B. Carbonic anhydrase in the membranes of microvilli in the tubules catalyzes the conversion of carbonic acid to carbon dioxide and water. C. Carbon dioxide is reabsorbed and converted in either the tubule cells or the red blood cells to carbonic acid, which dissociates to bicarbonate and H+. D. In addition to reabsorbing bicarbonate, the nephrons filter and secrete H+, which is excreted in the urine buffered by ammonium and phosphate buffers.

Chapter Summary Clinical Applications I. Diuretic drugs are used clinically to increase the urine volume and thus to lower the blood volume and pressure. A. Loop diuretics and the thiazides inhibit active Na+ transport in the ascending limb and early portion of the distal tubule, respectively. B. Osmotic diuretics are extra solutes in the filtrate that increase the osmotic pressure of the filtrate and inhibit the osmotic reabsorption of water. C. The potassium-sparing diuretics act on the distal tubule to inhibit the reabsorption of Na+ and secretion of K+. II. In glomerulonephritis the glomeruli can permit the leakage of plasma proteins into the urine. III. The technique of renal dialysis is used to treat people with renal insufficiency.