II. Kidney Physiology: Mechanisms of Urine Formation (pp. 969–984; Figs. 25.9–25.18; Table 25.1)
A. Step 1: Glomerular Filtration (pp. 969–974; Figs. 25.9–25.12)
1. Glomerular filtration is a passive, nonselective process in which hydrostatic pressure forces fluids through the glomerular membrane.
2. The net filtration pressure responsible for filtrate formation is given by the balance of glomerular hydrostatic pressure against the combined forces of colloid osmotic pressure of glomerular blood and capsular hydrostatic pressure exerted by the fluids in the glomerular capsule.
3. The glomerular filtration rate is the volume of filtrate formed each minute by all the glomeruli of the kidneys combined.
4. Maintenance of a relatively constant glomerular filtration rate is important because reabsorption of water and solutes depends on how quickly filtrate flows through the tubules.
5. Glomerular filtration rate is held relatively constant through intrinsic autoregulatory mechanisms, and extrinsic hormonal and neural mechanisms.
a. Renal autoregulation uses a myogenic control related to the degree of stretch of the afferent arteriole, and a tubuloglomerular feedback mechanism that responds to the rate of filtrate flow in the tubules.
b. Extrinsic neural mechanisms are stress-induced sympathetic responses that inhibit filtrate formation by constricting the afferent arterioles.
c. The renin-angiotensin mechanism causes an increase in systemic blood pressure and an increase in blood volume by increasing Na+ reabsorption.
B. Step 2: Tubular Reabsorption (pp. 974–978; Figs. 25.13–25.14, 25.18; Table 25.1)
1. Tubular reabsorption begins as soon as the filtrate enters the proximal convoluted tubule, and involves near total reabsorption of organic nutrients, and the hormonally regulated reabsorption of water and ions.
2. The most abundant cation of the filtrate is Na+, and reabsorption is always active.
3. Passive tubular reabsorption is the passive reabsorption of negatively charged ions that travel along an electrical gradient created by the active reabsorption of Na+.
4. Obligatory water reabsorption occurs in water-permeable regions of the tubules in response to the osmotic gradients created by active transport of Na+.
5. Secondary active transport is responsible for absorption of glucose, amino acids, vitamins, and most cations, and occurs when solutes are cotransported with Na+ when it moves along its concentration gradient.
6. Substances that are not reabsorbed or incompletely reabsorbed remain in the filtrate due to a lack of carrier molecules, lipid insolubility, or large size (urea, creatinine, and uric acid).
7. Different areas of the tubules have different absorptive capabilities.
a. The proximal convoluted tubule is most active in reabsorption, with most selective reabsorption occurring there.
b. The descending limb of the loop of Henle is permeable to water, while the ascending limb is impermeable to water but permeable to electrolytes.
c. The distal convoluted tubule and collecting duct have Na+ and water permeability regulated by the hormones aldosterone, antidiuretic hormone, and atrial natriuretic peptide.
C. Step 3: Tubular Secretion (p. 978)
1. Tubular secretion disposes of unwanted solutes, eliminates solutes that were reabsorbed, rids the body of excess K+, and controls blood pH.
2. Tubular secretion is most active in the proximal convoluted tubule, but occurs in the collecting ducts and distal convoluted tubules as well.
D. Regulation of Urine Concentration and Volume (pp. 978–983; Figs. 25.15–25.18)
1. One of the critical functions of the kidney is to keep the solute load of body fluids constant by regulating urine concentration and volume.
2. The countercurrent mechanism involves interaction between filtrate flow through the loops of Henle (the countercurrent multiplier) of juxtamedullary nephrons and the flow of blood through the vasa recta (the countercurrent exchanger).
a. Because water is freely absorbed from the descending limb of the loop of Henle, filtrate concentration increases and water is reabsorbed.
b. The ascending limb is permeable to solutes, but not to water.
c. In the collecting duct, urea diffuses into the deep medullary tissue, contributing to the increasing osmotic gradient encountered by filtrate as it moves through the loop.
d. The vasa recta aids in maintaining the steep concentration gradient of the medulla by cycling salt into the blood as it descends into the medulla, and then out again as it ascends toward the cortex.
3. Because tubular filtrate is diluted as it travels through the ascending limb of the loop of Henle, production of a dilute urine is accomplished by simply allowing filtrate to pass on to the renal pelvis.
4. Formation of a concentrated urine occurs in response to the release of antidiuretic hormone, which makes the collecting ducts permeable to water and increases water uptake from the urine.
5. Diuretics act to increase urine output by either acting as an osmotic diuretic or by inhibiting Na+ and resulting obligatory water reabsorption.
E. Renal Clearance (p. 984)
1. Renal clearance refers to the volume of plasma that is cleared of a specific substance in a given time.
2. Inulin is used as a clearance standard to determine glomerular filtration rate because it is not reabsorbed, stored, or secreted.
3. If the clearance value for a substance is less than that for inulin, then some of the substance is being reabsorbed; if the clearance value is greater than the inulin clearance rate, then some of the substance is being secreted. A clearance value of zero indicates the substance is completely reabsorbed.