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Lec. 1 Physiology of the Kidneys: After studying these lectures, you should be able to . . . 1. Describe the different regions of the nephron tubules and the location of the tubules in 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 define the terms transport maximum and renal plasma threshold. 9. Define the term 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. Describe the mechanism of Na++reabsorption in the distal tubule and explain why this reabsorption occurs together with the secretion of K+. 12. Describe the effects of aldosterone on the cortical portion of the collecting duct and explain how aldosterone secretion is regulated. 13. Explain how activation of the reninangiotensin- aldosterone system results in the stimulation of aldosterone secretion. 14. Explain how the interaction between plasma K+ and H+ concentrations affects the tubular secretion of these ions. 15. Describe the role of the kidneys in the regulation of acid-base balance. 1 Lec. 1 Function of the kidneys 1. Excretion of Metabolic Waste Products, Foreign Chemicals, Drugs, and Hormone Metabolites. The kidneys are the primary means for eliminating waste products of metabolism that are no longer needed by the body. These products include urea (from the metabolism of amino acids), creatinine (from muscle creatine), uric acid (from nucleic acids), end products of hemoglobin breakdown (such as bilirubin), and metabolites of various hormones. These waste products must be eliminated from the body as rapidly as they are produced. The kidneys also eliminate most toxins and other foreign substances that are either produced by the body or ingested, such as pesticides, drugs, and food additives. 2. Regulation of Water and Electrolyte Balances. For maintenance of homeostasis, excretion of water and electrolytes must precisely match intake. If intake exceeds excretion, the amount of that substance in the body will increase. If intake is less than excretion, the amount of that substance in the body will decrease. 3. Regulation of Acid-Base Balance. The kidneys contribute to acid-base regulation, along with the lungs and body fluid buffers, by excreting acids and by regulating the body fluid buffer stores. 4. Regulation of Erythrocyte Production. The kidneys secrete erythropoietin, which stimulates the production of red blood cells. One important stimulus for erythropoietin secretion by the kidneys is hypoxia. 5. Regulation of 1,25–Dihydroxyvitamin D3 Production. The kidneys produce the active form of vitamin D, 1,25- dihydroxyvitamin D3, by hydroxylating this vitamin at the “number 1” position. 6. Glucose Synthesis. The kidneys synthesize glucose from amino acids and other precursors during prolonged fasting, a process referred to as gluconeogenesis. The kidneys’ capacity to add glucose to the blood during prolonged periods of fasting rivals that of the liver. 7. Regulation of Arterial Pressure. The kidneys play a dominant role in long-term regulation of arterial pressure by excreting variable amounts of sodium and water. The kidneys also contribute to short-term arterial 2 Lec. 1 pressure regulation by secreting vasoactive factors or substances, such as renin, that lead to the formation of vasoactive products. Physiologic Anatomy of the Kidneys General Organization of the Kidneys and Urinary Tract The two kidneys lie on the posterior wall of the abdomen, outside the peritoneal cavity. Each kidney of the adult human weighs about 150 grams and is about the size of a clenched fist. The medial side of each kidney contains an indented region called the hilum through which pass the renal artery and vein, lymphatic, nerve supply, and ureter, which carries the final urine from the kidney to the bladder, where it is stored until emptied. The kidney is surrounded by a tough, fibrous capsule that protects its delicate inner structures. The nephron is the functional unit of the kidney responsible for the formation of urine. Each kidney contains more than a million nephrons. A nephron consists of small tubes, or tubules, and associated small blood vessels. Fluid formed by capillary filtration enters the tubules and is subsequently modified by transport processes; the resulting fluid that leaves the tubules is urine. Renal Blood Vessels Arterial blood enters the kidney through the renal artery, which divides into interlobar arteries that pass between the pyramids through the 3 Lec. 1 renal columns. Arcuate arteries branch from the interlobar arteries at the boundary of the cortex and medulla. A number of interlobular arteries radiate from the arcuate arteries into the cortex and subdivide into numerous afferent arterioles, which are microscopic. The afferent arterioles deliver blood into glomeruli—capillary networks that produce a blood filtrate that enters the urinary tubules. The blood remaining in a glomerulus leaves through an efferent arteriole, which delivers the blood into another capillary network—the peritubular capillaries surrounding the renal tubules. This arrangement of blood vessels is unique. It is the only one in the body in which a capillary bed (the glomerulus) is drained by an arteriole rather than by a venule and delivered to a second capillary bed located downstream (the peritubular capillaries). Blood from the peritubular capillaries is drained into veins that parallel the course of the arteries in the kidney. These veins are called the interlobular veins, arcuate veins, and interlobar veins. The interlobar veins descend between the pyramids, converge, and leave the kidney as a single renal vein, which empties into the inferior vena cava. Blood flow to the two kidneys is normally about 22 per cent of the cardiac output, or 1100 ml/min. as we said; the renal artery enters the kidney through the hilum and then branches progressively to form the radial arteries and afferent arterioles. The distal ends of the capillaries of each glomerulus coalesce to form the efferent arteriole, which leads to a second capillary network, the peritubular capillaries, that surrounds the renal tubules. The renal circulation is unique in that it has two capillary beds, the glomerular and peritubular capillaries, which are arranged in series and separated by the efferent arterioles, which help regulate the hydrostatic pressure in both sets of capillaries. High hydrostatic pressure in the glomerular capillaries (about 60 mm Hg) causes rapid fluid filtration, whereas a much lower hydrostatic pressure in the peritubular capillaries (about 13 mm Hg) permits rapid fluid reabsorption. By adjusting the resistance of the afferent and efferent arterioles, the kidneys can regulate the hydrostatic pressure in both the glomerular and the peritubular capillaries, thereby changing the rate of glomerular 4 Lec. 1 filtration, tubular reabsorption, or both in response to body homeostatic demands. Nephron Tubules The tubular portion of a nephron consists of a glomerular capsule, a proximal convoluted tubule, a descending limb of the loop of Henle, an ascending limb of the loop of Henle, and a distal convoluted tubule. 5 Lec. 1 The glomerular (Bowman’s) capsule surrounds the glomerulus. The glomerular capsule and its associated glomerulus are located in the cortex of the kidney and together constitute the renal corpuscle. The glomerular capsule contains an inner visceral layer of epithelium around the glomerular capillaries and an outer parietal layer. The space between these two layers is continuous with the lumen of the tubule and receives the glomerular filtrate. Filtrate that enters the glomerular capsule passes into the lumen of the proximal convoluted tubule. The wall of the proximal convoluted tubule consists of a single layer of cuboidal cells containing millions of microvilli; these microvilli increase the surface area for reabsorption. In the process of reabsorption, salt, water, and other molecules needed by the body are transported from the lumen, through the tubular cells and into the surrounding peritubular capillaries. The glomerulus, glomerular capsule, and convoluted tubule are located in the renal cortex. Fluid passes from the proximal convoluted tubule to the loop of Henle. This fluid is carried into the medulla in the descending limb of the loop and returns to the cortex in the ascending limb of the loop. Back in the cortex, the tubule again becomes coiled and is called the distal convoluted tubule. The distal convoluted tubule is shorter than the proximal tubule and has relatively few microvilli. The distal convoluted tubule terminates as it empties into a collecting duct. The two principal types of nephrons are classified according to their position in the kidney and the lengths of their loops of Henle. Nephrons 6 Lec. 1 that originate in the inner one-third of the cortex—called juxtamedullary nephrons because they are next to the medulla—have longer loops of Henle than the more numerous cortical nephrons, which originate in the outer two thirds of the cortex. The juxtamedullary nephrons play an important role in the ability of the kidney to produce concentrated urine. A collecting duct receives fluid from the distal convoluted tubules of several nephrons. Fluid is then drained by the collecting duct from the cortex to the medulla as the collecting duct passes through a renal pyramid. This fluid, now called urine, passes into a minor calyx. Urine is then funnelled through the renal pelvis and out of the kidney in the ureter. 7