Chapter VIII Excretion
The kidneys regulate the water and ionic composition of the body, excrete waste products and foreign chemicals, and secrete three hormones--renin, 1,25-dihydroxyvitamin D3, and erythropoietin.
Basic Renal Processes
The three basic renal processes are glomerular filtration, tubular reabsorption, and tubular secretion.
Urine formation begins with glomerular filtration-- approximately 180 L/day, which is essentially protein-free plasma into Bowman's capsule. Glomerular filtrate contains all the plasma substances, other than protein and substances bound to protein, in virtually the same concentrations as in plasma. Glomerular filtration is driven by the hydrostatic pressure in the glomerular capillaries and is opposed by both the hydrostatic pressure in Bowman's capsule and the osmotic force due to the proteins in the glomerular capillary plasma. About 20% of the renal plasma flow are converted to primary urine by ultrafiltration across glomerular capillaries.
As the filtrate moves through the tubules, certain substances are reabsorbed into the peritubular capillaries. Tubular reabsorption rates are generally very high for nutrients, ions and water, but are lower for waste products. Reabsorption may occur by carrier-mediated mechanisms or by diffusion. Many of the carrier-mediated systems manifest transport maximums, so that when the filtered load of a substance to be transported becomes very high, large amounts of the substance will escape reabsorption and appear in the urine. Diffusion occurs for some substances, to which the tubular epithelium is permeable, because water reabsorption creates tubule interstitium diffusion gradients for them. Tubular secretion, movement from the peritubular capillaries into the tubules, is a pathway in addition to glomerular filtration for a substance to gain entry to the tubule.
The proximal tubule reabsorbs most of the filtered Na+ and water; active reabsorption of some essential solutes such as glucose (typically by a Na+ gradient-coupled process); active secretion of some organic metabolic end products; active secretion of H+ which rids the body of its daily production of fixed acid and recovers filtered bicarbonate by conversion to CO2, which diffuses back into the peritubular capillaries.
The loop of Henle concentrates descending urine using salt removed from the ascending limb. The result is an osmotic gradient between the cortex and medulla of the kidney. The interstitial fluid in the medulla is further concentrated by entry of urea from the concentrated urine in the collecting ducts. The urine leaving the ascending limb of the loop of Henle is diluted as a result of the reabsorption of salt from it without osmotic movement of water.
The distal tubule recovers filtered Na+ by active transport, diluting the urine and causing other solutes, such as urea, to make up a larger percentage of the total solute content. The rate of Na+ reabsorption (and K+ secretion) is increased by the hormone aldosterone.
Regulation of Sodium and Water Balance
The body gains water via ingestion and internal production, and it loses water via urine, the gastrointestinal tract, and evaporation from the skin and respiratory tract (as insensible loss and sweat).For both water and sodium, the major homeostatic control point for maintaining stable balance is renal excretion. Approximately two-thirds of the body water is intracellular and one-third is extracellular. The amount of sodium in the body determines the extracellular volume.
Basic renal processes for sodium and water Sodium is freely filterable at the glomerulus, and its reabsorption is a primary active process dependent upon Na+ pump in the basolateral membranes of the tubular epithelium. Sodium reabsorption also drives, by cotransport, the secondary active reabsorption of glucose, amino acids, and chloride and, by countertransport, the secretion of hydrogen ions. Sodium reabsorption creates an osmotic gradient across the tubule, which drives water reabsorption by osmosis. Water reabsorption from the collecting ducts depends on the presence of the posterior pituitary hormone antidiuretic hormone (ADH), which increases the permeability of this segment to water. A large volume of dilute urine is produced when plasma ADH concentration and water reabsorption is low. A small volume of concentrated urine is produced by the renal countercurrent multiplier system when plasma ADH concentration is high. The active transport of sodium chloride by the ascending loop of HenIe causes a progressive concentration of the interstitial fluid of the medulla. This concentrated interstitium causes water to move out of the collecting ducts made highly permeable to water by ADH. The result is concentration of the collecting duct fluid and the urine.
Renal sodium regulation Sodium excretion is the difference between the amount of sodium filtered and the amount reabsorbed. Glomerular filtration rate (GFR), and therefore filtered load of sodium, is controlled by baroreceptor reflexes. Decreased vascular pressures cause decreased baroreceptors firing and increased sympathetic outflow to the renal arterioles, resulting in vasoconstriction and decreased GFR. The major control of tubular sodium reabsorption is the adrenal cortical hormone aldosterone, which stimulates sodium reabsorption in the late distal tubules and collecting ducts. The renin-angiotensin system is one of the major controllers of aldosterone secretion. Renin, the rate-limiting variable in the renin-angiotensin system, is secreted by the granular cells of the kidney juxtaglomerular apparatus and catalyzes, in the blood, the formation of angiotensin I from circulating angiotensinogen produced by the liver. Angiotensin I is then cleaved to yield angiotensin II, which acts on the adrenal cortex to stimulate aldosterone secretion.
trial natriuretic factor, secreted by cells in the atria in response to atrial distention, increases glomerular filtration rate and inhibits sodium reabsorption.
Renal water regulation Water excretion is the difference between the amount of water filtered and the amount reabsorbed. GFR regulation via the baroreceptor reflexes plays some role in regulating water excretion, but the major control is via antidiuretic hormone (ADH) control of water reabsorption. The posterior pituitary secretes ADH in response to increased osmolarity of plasma. Secretion of the hormone may be inhibited by increased atrial stretch. ADH increases water reabsorption across the wall of the collecting duct, stimulating water conservation and resulting in the production of hyperosmotic urine. ADH could be said to be the hormone of water conservation. The steroid hormone aldosterone is secreted by the adrenal cortex in response to a regulatory cascade that begins with secretion of renin from the juxtaglomerular apparatus. Renin catalyzes the conversion of plasma angiotensinogen to angiotensin I. Angiotensin II is produced by an endothelial-converting enzyme. Angiotensin III is produced by the adrenal cortex and stimulates its secretion of aldosterone. Secretion of renin increases in response to decreases in glomerular filtration or the Na+ concentration of the filtrate. Aldosterone increases the recovery of filtered Na+ in the distal tubule. Under normal conditions increases in total body Na+ are matched so rapidly by water retention that the main effect of the hormone is to increase extracellular fluid volume. All filtered K+ is reabsorbed in the proximal tubule and loop of HenIe. Thus the distal tubule's secretion of K+ is the regulatory step in renal K+ handling. Plasma K+ directly stimulates aldosterone release; aldosterone stimulates distal tubular K+ secretion. If Na+ reabsorption is constant, K+ secretion and H+ secretion behave as if they were competitive; both are stimulated by aldosterone.
Regulation of Potassium, Calcium, and Hydrogen Ion
Regulation of potassium A person remains in potassium balance by excreting an amount of potassium in the urine equal to the amount ingested minus the amounts lost in the feces and sweat. Potassium is freely filterable at the glomerulus and undergoes both reabsorption and secretion, the latter being the major controlled variable. When body potassium is increased, aldosterone secretion is stimulated by an increased plasma concentration of potassium, and the increased aldosterone then stimulates potassium secretion.
Regulation of calcium Plasma calcium concentration is maintained by control of urinary excretion, gastrointestinal absorption, and movement into and out of bone. Parathyroid hormone increases plasma calcium concentration by influencing these processes. It stimulates tubular reabsorption of calcium, and movement of calcium out of bone.
Regulation of hydrogen ion Total-body balance of hydrogen ions is the result of both metabolic productions of these ions and net gains or losses via the gastrointestinal tract and urine. A stable balance is achieved by regulation of urinary losses. Buffering is a means of minimizing changes in hydrogen ion concentration by combining these ions reversibly with anions such as bicarbonate and intracellular proteins. The kidneys not only excrete hydrogen ions but also reabsorb bicarbonate. Both processes require tubular hydrogen ion secretion in a process catalyzed by carbonic anhydrase. The excreted hydrogen ions are in combination with urinary buffers, notably ammonia produced and secreted by the tubules.
Concentration and Dilution of Urine
In the presence of ADH, the walls of the collecting duct are permeable to water and the urine in the collecting duct is concentrated by osmotic water movement into the medullary interstitial spaces. Some urea is reabsorbed in this process, contributing to osmotic movement of water and to the solute content of the medullary interstitial fluid. Decreasing the ADH concentration increases the amount of water that is not reabsorbed, making the final urine more dilute. The loop shape of the vasa recta mirrors that of the loops of Henle. Its function is to preserve the medullary osmotic gradient by counter current exchange. Plasma descending the vasa recta equilibrates with the concentrated medullary interstitial fluid. As the plasma ascends the loop, it equilibrates with the less and less concentrated interstitial fluid and leaves the kidney at the same concentration as normal plasma. In this way, the fluid and solute reabsorbed in the medullary portions of the nephrons are returned to the general circulation and the osmotic gradient is not disrupted.
Micturition
Micturition occurs when bladder distention stimulates stretch receptors that trigger spinal reflexes leading to parasympathetically mediated contraction of the bladder smooth muscle. Voluntary control is exerted chiefly by stimulating or inhibiting the nerves to the pelvic diaphragm.
Urination is the result of reflexive contraction of the bladder smooth muscle accompanied by opening of the external sphincter (skeletal muscle). The reflex is modulated by pathways from the brain to give voluntary control.
