a. The kidneys filter blood plasma, separate wastes, return useful materials to the blood, and eliminate the wastes.

b. They regulate blood volume and pressure.

c. They regulate the osmolarity of the body fluids.

d. They secrete renin, a hormone which activates mechanisms that control blood pressure and electrolyte balance.

e. They secrete erythropoietin, which controls RBC production and oxygen-carrying capacity of the blood.

f. They help to regulate acid-base balance of the body fluids.

g. They control calcium homeostasis through their role in synthesizing calcitrol.

h. They detoxify superoxides, free radicals, and drugs.

i. They deaminate amino acids in times of starvation for use in energy (gluconeogenesis) pathways (the amino portion is excreted as ammonia).

a. Metabolism produces a great quantity of wastes that are lethal to cells if allowed to accumulate.

b. Two of the most toxic metabolic wastes are carbon dioxide and nitrogenous wastes, most of which is urea (a product of protein metabolism). Other nitrogenous wastes in the urine are uric acid and creatinine, produced by the catabolism of nucleic acids and creatinine phosphate, respectively.

a. One osmole is 1 mole of dissolved solute particles. A 1 molar (M) solution of NaCl, for example, yields 1 mole of sodium ions and 1 mole of chloride ions per liter. Both ions affect osmosis and must be counted separately in a measure of osmotic concentration. Thus 1 M NaCl = 2 osm/L.

b. Osmolality is the number of osmoles of solute per kilogram of water.

c. Osmolarity is the number of osmoles per liter of solution. Most clinical calculations are based on osmolarity because it is easier to measure the volume of a solution than the weight of water it contains.

d. Physiologic concentrations are often expressed in milliosmoles per liter (mOsm/L).

a. The lateral surface of the kidney is convex, while the medial surface is concave with a hilum carrying renal nerves and blood vessels.

a. Extensions of the cortex (renal columns) project toward the sinus, dividing the medulla into 6-10 renal pyramids. Each pyramid is conical with a blunt point called the papilla facing the sinus.

b. The papilla is nestled into a cup called a minor calyx, which collects its urine. Two or three minor calyces merge to form a major calyx. The major calyces merge to form the renal pelvis.

a. Most components of the nephron are within the cortex. Nephrons closer to the medulla, called juxtamedullary nephrons, differ slightly in structure and function than cortical nephrons, located closer to the surface.

a. The renal fraction of the cardiac output is 21%. Each kidney is supplied by a renal artery, entering the hilum that gives rise to a few interlobar arteries that penetrate the renal columns and travel between the pyramids to the boundary between the cortex and medulla.

b. At this boundary, interlobar arteries branch to form arcuate arteries from which interlobular arteries arise.

c. As an interlobular artery ascends through the cortex, a series of afferent arterioles arise from it, each supplying blood to a single nephron. It ends in a rounded cluster of capillaries, called a glomerulus where urine production begins.

d. The glomerulus is drained by an efferent arteriole, which leads to the peritubular capillaries surrounding the renal tubule.

e. Blood flows from the peritubular capillaries into the interlobular veins, arcuate veins, interlobar veins, and the renal veins, which drain blood from the kidney and returns it to the vena cava.

f. The renal medulla is supplied by the vasa recta - long straight vessels that arise from the efferent arterioles of the juxtamedullary nephrons.

a. The renal corpuscle consists of a glomerulus enclosed in a two-layered glomerular (Bowman's) capsule. The visceral layer of the glomerular capsule has special cells, called podocytes, wrapped around the capillaries.

a. The renal tubule is a duct that leads away from the glomerular capsule and ends at the tip of a medullary pyramid. It consists of the proximal convoluted tubule, nephron loop, distal convoluted tubule, and collecting duct.

b. The proximal convoluted tubule (PCT) is the longest and most coiled region of the renal tubule, and arises from the glomerular capsule. It has prominent microvilli that aid the absorption occurring here.

c. The nephron loop (loop of Henle) is a U-shaped portion of the renal tubule. The descending limb passes into the medulla and forms an ascending limb that returns to the cortex. Juxtamedullary nephrons have long loops; cortical nephrons have shorter loops.

d. The distal convoluted tubule (DCT) is shorter and less convoluted than the PCT and marks the end of the nephron.

e. The DCTs of several nephrons merge to form a collecting duct that passes down into the medulla. Urine in the collecting duct will be passed to a papillary duct, then to a minor and major calyx, to the renal pelvis, and out the ureter.

a. The juxtaglomerular apparatus is a structure located where the afferent and efferent arterioles meet, and enables autoregulation of blood filtration.

a. The fenestrated epithelium of the capillary that allows these cells to be more permeable than endothelial cells elsewhere.

b. The basement membrane is a proteoglycan gel that excludes molecules larger than 8 nm. Some smaller molecules are also prevented from passing by a negative electrical charge on the proteoglycans.

c. The arm-like podocytes of the glomerular capsule have little extensions called foot processes (pedicels) that, in turn, have negatively charged filtration slits, which are an additional obstacle to large anions.

a. The blood pressure (BP) is higher here than elsewhere. This results from the fact that the afferent arteriole is substantially larger than the efferent arteriole.

b. The hydrostatic pressure in the capsular space results from the high rate of filtration occurring here and the continual accumulation of fluid in the capsule.

c. The colloid osmotic pressure (COP) of the blood is the same here as elsewhere.

d. The glomerular filtrate is almost protein-free and has no significant COP.

a. If GFR is too high, urine output rises and creates a threat of dehydration and electrolyte depletion.

b. If GFR is too low, fluid flows sluggishly through the tubules, and they reabsorb wastes that should be eliminated in the urine.

c. The only way to adjust GFR from moment to moment is to change glomerular blood pressure.

a. Renal autoregulation is the ability of the kidneys to maintain a relatively stable GFR in spite of changes in arterial blood pressure.

b. The nephron has two ways to prevent drastic changes in GFR when blood pressure rises: it can constrict the afferent arteriole and reduce blood flow into the glomerulus, or it can dilate the efferent arteriole and allow the blood to flow out more easily. Conversely if blood pressure falls, the nephron can compensate by either dilating the afferent arteriole or constricting the efferent arteriole.

c. The juxtaglomerular apparatus (JGA) that allows the nephron to compensate for pressure differences is made up of these cells: (1) juxtaglomerular (JG) cells that are enlarged smooth muscle cells of the afferent arteriole that can dilate or constrict and secrete renin in response to a drop in BP; (2) the macula densa, a patch of slender epithelial cells of the distal tubule that apparently monitor the salinity of the tubular fluid in the DCT; and (3) mesangial cells between the afferent and efferent arterioles, whose role is not yet understood.

d. Two important points must be noted about renal autoregulation. First, it does not completely prevent changes in the GFR. Second, renal autoregulation cannot compensate for extreme blood pressure variations.

a. Sympathetic nerve fibers richly innervate the renal blood vessels. In strenuous exercise or acute conditions (circulatory shock), the sympathetic nervous system and adrenal epinephrine stimulate the afferent arterioles to constrict. This reduces GFR and urine production, while it redirects blood from the kidneys to the heart, brain, and skeletal muscles.

a. When BP drops, the JG cells secrete renin that acts to convert angiotensinogen into angiotensin I. As angiotensin I circulates through the lungs, angiotensin-converting enzyme (ACE) converts it to angiotensin II.

b. Angiotensin II has multiple effects. It raises blood pressure by widespread vasoconstriction. It constricts the efferent arterioles and prevents the glomerular blood pressure from dropping too low. It increases tubular reabsorption of water, it stimulates the secretion of aldosterone, and stimulates the sense of thirst.

a. While the glomerular capillaries are filtering the plasma, the peritubular capillaries are engaged in tubular reabsorption. Since fluid has been extracted from the blood at the glomerulus, the blood remaining in the capillary has an unusually high colloid pressure (COP) downstream from this point. Water is reabsorbed by osmosis and carries other solutes along by solvent drag.

b. The PCT reabsorbs a greater variety of chemicals than any other part of the nephron. Some pass through the cytoplasm of the cell via the transcellular route, while others slip between epithelial cells using a paracellular route.

c. Sodium is reabsorbed using both routes. There is a steep concentration gradient favoring the diffusion of sodium into the epithelial cell. Some enters the cell by simple diffusion through membrane channels, and some are reabsorbed by facilitated diffusion using transport proteins in the apical plasma membrane.

d. Some of the apical sodium carriers bind simultaneously to a sodium ion and a glucose molecule and transport them both into the cell. Such a carrier protein is called the sodium-dependent glucose transporter (SDFT). Normally all glucose in the tubular fluid is reabsorbed and there is none in the urine.

e. Amino acids are reabsorbed in the same was as glucose using apical sodium carriers.

f. Sodium reabsorption makes the ICF and ECF hypertonic to the tubular fluid. Water follows sodium by diffusion through the paracellular route and by osmosis through the transcellular route. In the PCT water is reabsorbed by a constant rate called obligatory water reabsorption.

g. Chloride is reabsorbed along both the paracellular and transcellular routes. Its reabsorption is favored by two factors: (1) negative chloride ions tend to follow the positive sodium ions by electrostatic attraction, and (2) water reabsorption raises the Cl^- concentration in the tubular fluid, creating a gradient favorable to Cl^- reabsorption.

h. Potassium, magnesium, and variable amounts of calcium pass through the paracellular route by solvent drag.

i. The glomerulus filters a small amount of protein from the blood. The PCT reclaims it by pinocytosis, hydrolyzes it to amino acids, and releases these to the ECF by facilitated diffusion.

j. Nitrogenous wastes are dealt with in several ways. Urea diffuses through the tubule epithelium with water. The nephron as a whole reabsorbs 40-60% of the urea in the tubular fluid, but since it reabsorbs 99% of the water, urine has a substantially higher urea concentration than blood or glomerular filtrate. The PCT reabsorbs nearly all the uric acid entering it, but later parts of the nephron secrete it back to the tubular fluid. Creatinine is not reabsorbed at all because there are no transport proteins for it. All creatinine filtered by the glomerulus is excreted in the urine.

a. There is a limit to the amount of solute that the renal tubule can reabsorb because there are limited numbers of transport proteins in the plasma membranes. If all the transporters are occupied as solute molecules pass through, some solute will remain in the tubular fluid and appear in the urine.

a. Tubular secretion is a process in which the renal tubule extracts chemicals from the capillary blood and secretes them into the tubular fluid. Tubular secretion serves the purposes of waste removal and acid-base balance. The secretion of hydrogen and bicarbonate ions serves to regulate pH.

a. Aldosterone secretion is stimulated by a drop in blood sodium or raise in potassium concentration.

b. The general effect of aldosterone is to cause the DCT and cortical portion of the collecting duct to reabsorb more sodium and to secrete more potassium. Thus the urine volume is reduced. Salt and water reabsorption helps to maintain blood volume and pressure.

a. Atrial natriuretic factor (ANF) is secreted by the atrial myocardium of the heart in response to high blood pressure. It inhibits sodium and water reabsorption, increasing the output of both in the urine, and thus reducing blood volume and pressure.

a. The osmolarity of the cellular fluid is four times as high near the renal papilla as it is in the cortex.

b. The medullary portion of the CD is permeable to water but not to NaCl. Therefore, as urine passes down the CD through the increasingly salty medulla, water leaves the tubule by osmosis.

a. In a state of full hydration, ADH is not secreted and the cortical part of the CD reabsorbs salt without reabsorbing water, leaving the water to be excreted.

b. In a state of dehydration, ADH is secreted, the medullary portion of the CD reabsorbs water, and the urine is more concentrated.

a. Chemical composition of urine is indicated in Table 23.1, p. 853.

a. Excessive urine output is called polyuria.

b. Scanty urine output is oliguria. An output of less than 400 mL/day is insufficient and can lead to azotemia.

a. Diabetes is chronic polyuria resulting from various metabolic disorders. In most cases, the polyuria results from a high concentration of glucose in the renal tubule.

b. Diabetes mellitus, pituitary diabetes, and adrenal diabetes, the high glucose concentration in the tubule is a result of hyperglycemia.

a. Diuretics are chemicals that increase urine volume. They are used for treating hypertension and congestive heart failure because they reduce overall fluid volume.

b. Diuretics work by either increasing glomerular filtration or reducing tubular reabsorption. Caffeine falls into the former category; alcohol into the latter (alcohol suppresses the release of ADH).

c. Many diuretic drugs produce osmotic diuresis by inhibiting sodium reabsorption.

a. Renal clearance is the volume of blood plasma from which a particular waste is removed in 1 minute.

b. Renal clearance can be measured indirectly by collecting samples of blood and urine, measuring the waste concentration in each, and measuring the urine output.

a. Measuring GFR requires a substance that is not secreted or reabsorbed at all. Garlic and artichoke produce inulin, a polymer of glucose that is suitable.

b. All inulin filtered by the glomerulus remains in the renal tubule and appears in the urine; none is reabsorbed, and the tubule does not secrete it. For this solute, GFR is equal to the renal clearance.

a. Its muscularis, called the detrusor muscle, consists of three layers of smooth muscle.

b. The mucosa has a transitional epithelium, and in the relaxed bladder it has conspicuous wrinkles called rugae.

c. The openings of the two ureters and the urethra mark a triangular area called the trigone on the bladder floor.

a. In females, it is 3-4 cm long and its opening, the external urethral orifice, lies between the vaginal orifice and clitoris.

b. The male urethra is 18 cm long and has three regions: prostatic urethra, membranous urethra, and penile urethra.

CHAPTER ESSAY: Renal Insufficiency and Hemodialysis (p. 858; Fig. E.1)