RENAL SYSTEM
B. Urine Formation
Urine formation involves the following physiologic pro- cesses: filtration, reabsorption, and secretion.
1. Filtration
a. Fluid and various substances, known as the glomerular filtrate, are filtered from the plasma through the porous walls of the glomerular cap- illaries into Bowman’s capsule and on to the renal tubules. Glomerular filtrate is primarily composed of water; it is essentially the same
substance as blood plasma except for the larger protein molecules, such as albumin, because they are largely unable to move through the fil- tration barrier.
b. The pathway for filtration is through capil- lary fenestrations across the basement membrane and through slit passages. The ability to resist passing and to pass through filtration pathways depend on size, shape, and electrical charge of the molecules. Albumin (protein) molecules are too large to permeate the glomerular membrane, creating a high osmotic pressure that opposes orthostatic filtration from the vascular space.
c. The “forcing” pressure, or filtration pressure, is the net pressure acting to force substances out of the glomerulus.
i. The primary force is the hydrostatic pres- sure of the blood inside the capillaries gener- ated by the pumping action of the heart.
ii. The secondary forces are the oncotic pressure of the plasma in the glomerular capillaries and the hydrostatic pressure in Bowman’s capsule.
GLOMERULUS WITHIN BOWMAN’S
CAPSULE STRUCTURE
FUNCTION
TONICITY OF FLUID (WITHIN
DUCTS)
Filtration Reabsorption of Na+(majority) Glucose K+ Amino acids HCO3– PO4– UreaH2O(ADH not required)
Concentration of urine (countercurrent
mechanism)
PROXIMAL TUBULE LOOP OF HENLE DISTAL TUBULE COLLECTING DUCT
Secretion of H+
Foreign substances
Isotonic Isotonic Isotonic or
hypotonic Final concentration Hypertonic
Hypotonic Descending loop Water reabsorption Na+diffuses in Ascending loop Na+reabsorbed (active transport) Water stays in
Secretion of Reabsorption of Na+
H2O (ADH required)
Reabsorption or Secretion of
K+ K+
H+ H+
NH3+ NH3+
Na+
Some drugs Urea HCO2–
Reabsorption of H2O (ADH required)
FIGURE 5.2 Tubular components of the nephron.
ADH, antidiuretic hormone.
Source: From Wong, D. L., Hockenberry-Eaton, M., Wilson, D., Winkelstein, M. L., Ahmann, E.,
& DiVito-Thomas, P. (1999). Whaley & Wong’s nursing care of infants and children (6th ed.).
St. Louis, MO: Mosby.
d. Regulation of glomerular filtration rate (GFR) i. Renal blood flow (RBF) and GFR must remain relatively constant over a wide range of perfusion pressures and in various physio- logical states such as disease. This is referred to as autoregulation. Numerous neural and hormonal factors can alter RBF, such as renal vasoconstrictors that decrease RBF, includ- ing endothelin, angiotensin II, thromboxane, alpha-adrenergic receptor stimulators, vaso- pressin, and catecholamines. Vasodilators that may relax renal vascular smooth mus- cle include prostaglandins, atrial peptides, bradykinin, fenoldopam, and nitric oxide.
Failure of these mechanisms can lead to renal dysfunction in all of the disease states discussed in this chaper.
ii. Changes in filtration pressure can directly affect GFR. Factors affecting filtration pressure, and thus the GFR, include vaso- constriction or vasodilation of afferent and efferent arterioles, blood flow rate, tubule obstruction, and changes in serum osmotic pressure. RBF is controlled by sympathetic nerve impulses that constrict arterioles. The effect on GFR depends on which arteriole (afferent or efferent) is constricted (Table 5.1).
iii. Vasodilation and vasoconstriction are autoregulatory responses to changes in sys-
temic arterial pressure. They occur to main- tain constant RBF and a stable GFR. A distal tubular feedback mechanism ensures con- stant delivery of filtrate to the distal tubule.
Failure of this autoregulatory response can be due to obstruction, trauma, dehydration, or disease.
iv. The effect of shock on GFR and renal function is detailed in Figure 5.3.
e. Measuring filtration. Clearance is the volume of a specific substance filtered from the plasma over a designated time, generally:
Clearance (mL/min/1.73m) = Concentration of substance in urine ×
Volume of urine collected/plasma concentration of that substance i. Substances used to assess GFR include creatinine, inulin (nonmetabolizable sugar), radioisotopes, radiocontrast agents, and cystatin-C.
ii. GFR as estimated by creatinine clear- ance alone is less accurate. Creatinine is an endogenous waste product that is produced by the muscles and excreted by the kidneys.
Estimates of GFR using creatinine clearance and cystatin-C together are more accurate, especially in children (Traynor, Mactier, Geddes, & Fox, 2006).
TABLE 5.1 Factors Affecting GFR
Factors Physiologic Response Net Effect on GFR
Afferent arteriole vasoconstriction,
efferent arteriole vasodilation, or both Decreased blood flow
Decreased glomerular hydration pressure
Decrease
Afferent arteriole vasodilation or
efferent arteriole vasoconstriction Blood backs up in the glomerulus
Increased hydrostatic pressure Increase Decrease in plasma protein
concentration Decreased plasma osmotic pressure Increase
Slow blood flow Larger proportions of the plasma filter out of the glomerulus
Plasma osmotic pressure rises
Decrease
Rapid blood flow Less change in plasma osmotic pressure Increase Tubular obstruction Fluid backs up in the renal tubules
Hydrostatic pressure increases in Bowman’s capsule
Decrease
GFR, glomerular filtration rate.
DEVELOPMENTAL PHYSIOLOGY AND CLINICAL ASSESSMENT OF KIDNEY FUNCTION ■ 449
iii. GFR as measured by creatinine clearance
1) First week of life. GFR = 15 to 20 mL/
min/1.73 m2
2) At the second week of life. GFR = 35 to 40 mL/min/1.73 m2
3) At 6 months. GFR = 60 mL/min/1.73 m2 4) At 1 year. GFR = 80 to 120 mL/
min/1.73 m2
iv. The filtration fraction (FF) is the per- centage of fluid filtered into Bowman’s cap- sule by the glomerulus in relationship to the total renal plasma flow (normal = 20%).
v. Alteration in GFR occurs with decreased renal perfusion, changes in glomerular per- fusion pressures (e.g., shock, glomerular nephritis), and decreases in plasma oncotic pressure (e.g., nephrotic syndrome).
2. Tubular Reabsorption. As fluid flows along the nephron, past the cells of the tubular wall, sub- stances are reabsorbed from the renal tubule and returned to the blood via the peritubular capillaries.
a. Most of tubular reabsorption occurs in the proximal tubule. By the time the filtrate reaches the end of the proximal tubule, two thirds of the water and virtually all the nutrients have been reabsorbed and returned to the blood. The prox- imal tubules play a role in acid–base balance and regulation of calcium, magnesium, and phos- phorus. The proximal tubules have active trans- port systems for secretion of organic acids and bases from blood to tubule lumen.
b. The tubular cells lining the walls of the prox- imal tubules are surrounded by two different membranes that aid in water and solute reab- sorption. The convoluted portion of the proxi- mal tubule has a brush-like border of microvilli that greatly increases surface area exposed to glomerular filtrate and enhances reabsorption.
The basolateral membrane has no microvilli but has an abundance of sodium and potassium pumps and other diffusion transport systems for glucose and amino acids.
c. Segments of the renal tubule use partic- ular modes of transport to reabsorb certain substances. Substances reabsorbed by active transport depend on carriers. If the amount of substance exceeds the number of carriers (renal tubular threshold), the remaining substance will remain in the filtrate and be excreted in urine (e.g., glucosuria). Glucosuria only occurs when plasma glucose levels exceed 180 mg/dL.
d. Fluid reabsorption is determined by the net sodium reabsorption. If the GFR decreases, net sodium reabsorption decreases and fluid reab- sorption decreases. If the GFR increases, net sodium reabsorption increases and fluid reab- sorption increases.
e. Several factors enhance the rate of fluid reabsorption from the renal tubule. The effer- ent arteriole is narrower than the peritubular capillary; therefore, blood flowing from the efferent arteriole to the peritubular capillary is under relatively low pressure. The wall of the renal capillary is more permeable than other capillaries.
Glomerular hydrostatic pressure falls
↓
Epithelial cells of the tubules do not receive sufficient nutrients to support the high metabolic rate
↓
Cells die; tubular necrosis occurs
↓ ↓
Renal function may be lost Renal tubular epithelial cells regenerate
↓
Renal function is recovered FIGURE 5.3 Renal response to shock.
f. The prime “mover” for most of the proximal tubular transport is the active transport of sodium. Water is reabsorbed by osmosis in response to the reabsorption of sodium ions by active transport. Amino acids and glucose are cotransported (reabsorbed) with sodium into the interstitial fluid and eventually to capillaries.
When sodium is reabsorbed from the tubule, it takes chloride with it, changing the osmotic gra- dient and favoring the reabsorption of water into the interstitium and eventually to the capillaries.
When water is absorbed from the tubule, the concentration of the remaining solutes increases, therefore increasing the diffusion of other sol- utes into the interstitial space and eventually to the capillaries.
g. Measuring reabsorption. The amount of solute reabsorbed is the difference between the amount of solute filtered into the glomerulus and the amount of solute excreted in the urine (assuming the amount filtered is greater than the amount excreted).
3. Tubular secretion is the process by which certain substances are removed from the blood or plasma of the peritubular capillary and added to the fluid of the renal tubule through active or passive transport.
a. Certain organic compounds (such as pen- icillin, creatinine, and histamine) are actively secreted into tubular fluid by the epithelium of the proximal convoluted segment.
b. Hydrogen ions are secreted by the distal segment and the collecting ducts. Hydrogen ion secretion plays an important role in acid–base balance.
c. Potassium ions are secreted into tubular fluid because of the electrochemical attraction created by sodium reabsorption.
d. Measuring secretion. The amount of solute secreted is the difference between the amount of solute filtered into the glomerulus and the amount of solute excreted in the urine (assum- ing the amount filtered is less than the amount excreted).