On-line P12 Learning Center
The Kidneys and Regulation of Water and Inorganic Ions
SECTION A: BASIC PRINCIPLES OF RENAL PHYSIOLOGY
- FUNCTIONS AND STRUCTURE OF THE KIDNEYS AND URINARY SYSTEM
- The kidneys regulate the water and ionic composition of the body, excrete waste products, excrete foreign chemicals, produce glucose during prolonged fasting, and secrete three hormones--renin, 1,25-dihydroxyvitamin D, and erythropoietin. The first three functions are accomplished by continuous processing of the plasma.
- Each nephron in the kidneys consists of a renal corpuscle and a tubule.
- Each renal corpuscle comprises a capillary tuft, termed a glomerulus, and a Bowman's capsule, into which the tuft protrudes.
- The tubule extends out from Bowman's capsule and is subdivided into many segments, which can be combined for reference purposes into four: proximal tubule, loop of Henle, distal convoluted tubule, and collecting duct. Multiple tubules join, beginning at the level of the collecting ducts, and empty into the renal pelvis, from which urine flows through ureters to the bladder.
- Each glomerulus is supplied by an afferent arteriole, and an efferent arteriole leaves the glomerulus to branch into peritubular capillaries, which supply the tubule.
- BASIC RENAL PROCESSES
- The three basic renal processes are glomerular filtration, tubular reabsorption,
and tubular secretion. In addition, the kidneys synthesize and/or catabolize
certain substances. The excretion of a substance is equal to the amount
filtered plus the amount secreted minus the amount reabsorbed.
- Urine formation begins with glomerular filtration (approximately 180 L/day) of essentially
protein-free plasma into Bowman's capsule.
- Glomerular filtrate contains all plasma substances, other than proteins and substances bound to proteins, 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.
- As the filtrate moves through the tubules, certain substances are reabsorbed into the peritubular capillaries.
- Substances to which the tubular epithelium is permeable are absorbed by diffusion because water reabsorption creates tubule-interstitium concentration gradients for them.
- Tubular reabsorption rates are generally very high for nutrients, ions, and water but are lower for waste products. Reabsorption may occur by diffusion or by mediated transport.
- Many of the mediated-transport systems manifest transport maximums, so that when the filtered load of a substance exceeds the transport maximum, large amounts may appear in the urine.
- 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 clearance of any substance can be calculated by dividing the mass of the substance excreted per unit time by the plasma concentration of the substance. GFR can be measured by means of the inulin clearance and estimated by means of the creatinine clearance.
- In the basic micturition reflex bladder distention stimulates stretch receptors that trigger spinal reflexes leading to contraction of the detrusor muscle, mediated by parasympathetic neurons, and relaxation of the external urethral sphincter, mediated by inhibition of the motor neurons to this muscle.
- Voluntary control is exerted via descending pathways to the parasympathetic nerves supplying the detrusor muscle and the motor nerves supplying the external urethral sphincter.
SECTION B: REGULATION OF SODIUM, WATER, AND POTASSIUM BALANCE
- TOTAL-BODY BALANCE OF SODIUM AND WATER
- The body gains sodium and chloride by ingestion and loses them via the skin (in sweat), gastrointestinal tract, and urine.
- 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.
- 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,K-ATPase pumps in the basolateral membranes of the tubular epithelium.
- Sodium entry into the cell from the tubular lumen is always passive. Depending on the tubular segment it is either through channels or by cotransport or countertransport with other substances.
- Sodium reabsorption creates an osmotic difference across the tubule, which drives water reabsorption.
- Water reabsorption is independent of the posterior pituitary hormone vasopressin until the collecting ducts, the water-permeability of which is increased by this hormone. A large volume of dilute urine is produced when plasma vasopressin concentration, and hence water reabsorption by the collecting ducts, is low.
- A small volume of concentrated urine is produced by the renal countercurrent multiplier system when plasma vasopressin concentration is high.
- The active transport of sodium chloride by the ascending loop of Henle causes a progressive concentration of the interstitial fluid of the medulla but a dilution of the luminal fluid.
- Vasopressin increases the permeability of the cortical collecting ducts to water, and so water is reabsorbed by this segment until the luminal fluid is isoosmotic to cortical interstitial fluid.
- The luminal fluid then enters and flows through the medullary collecting ducts, and the concentrated medullary interstitium causes water to move out of these ducts, made highly permeable to water by vasopressin. 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.
- GFR, and hence the filtered load of sodium, are controlled by baroreceptor reflexes. Decreased vascular pressures cause decreased baroreceptor firing and hence increased sympathetic outflow to the renal arterioles, resulting in vasoconstriction and decreased GFR. These changes are generally relatively small under most physiological conditions.
- The major control of tubular sodium reabsorption is the adrenal cortical hormone aldosterone, which stimulates sodium reabsorption in the cortical collecting ducts.
- The renin-angiotensin system is one of the two major controllers of aldosterone secretion. When extracellular volume decreases, renin secretion is stimulated by three inputs: (1) stimulation of the renal sympathetic nerves to the juxtaglomerular cells by extrarenal baroreceptor reflexes; (2) pressure decreases sensed by the juxtaglomerular cells, themselves acting as intrarenal baroreceptors; and (3) a signal generated by low sodium or chloride concentration in the lumen of the macula densa.
- Many other factors influence sodium reabsorption. One of these, atrial natriuretic factor, is secreted by cells in the atria in response to atrial distention; it inhibits sodium reabsorption and it also increases GFR.
- 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 vasopressin-mediated control of water reabsorption.
- Vasopressin secretion by the posterior pituitary is controlled by cardiovascular baroreceptors and by osmoreceptors in the hypothalamus.
- Via the baroreceptor reflexes, a low extracellular volume stimulates vasopressin secretion and a high extracellular volume inhibits it.
- Via the osmoreceptors, a high body-fluid osmolarity stimulates vasopressin secretion and a low osmolarity inhibits it.
- THIRST AND SALT APPETITE
- Thirst is stimulated by a variety of inputs, including baroreceptors, osmoreceptors, and angiotensin II.
- Salt appetite is not of major regulatory importance in people.
- POTASSIUM REGULATION
- 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 renal corpuscle and undergoes both reabsorption and secretion, the latter occurring in the cortical collecting duct and being the major controlled variable determining potassium excretion.
- When body potassium is increased, extracellular potassium concentration increases. This increase acts directly on the cortical collecting ducts to stimulate potassium secretion and also stimulates aldosterone secretion, the increased plasma aldosterone then also stimulating potassium secretion.
SECTION C: CALCIUM REGULATION
- EFFECTOR SITES FOR CALCIUM HOMEOSTASIS
- The effector sites for the regulation of plasma calcium concentration are bone, the gastrointestinal tract, and the kidneys.
- Approximately 99 percent of total-body calcium is constrained in bone as minerals on a collagen matrix.
- Calcium is actively absorbed by the gastrointestinal tract, and this process is under hormonal control.
- The amount of calcium excreted in the urine is the difference between the amount filtered and the amount reabsorbed, the latter process being under hormonal control.
- HORMONAL CONTROLS
- Parathyroid hormone increases plasma calcium concentration by influencing all the effector sites.
- It stimulates tubular reabsorption of calcium, bone resorption with release of calcium, and formation of the hormone 1,25-dihydroxyvitamin D, which stimulates calcium absorption by the intestine.
- It also inhibits the tubular reabsorption of phosphate, and the lowered plasma phosphate facilitates calcium movement out of bone.
- Vitamin D is formed in the skin or ingested and then undergoes hydroxylations in the liver and kidneys, in the latter under stimulation by parathyroid hormone, to the active form, 1,25-dihydroxyvitamin D.
SECTION D: HYDROGEN-ION REGULATION
- SOURCES OF HYDROGEN-ION GAIN OR LOSS
- Total-body balance of hydrogen ions is the result of both metabolic production of these ions and of metabolic gains or losses via the gastrointestinal tract and urine.
- A stable balance is achieved by regulation of urinary losses.
- BUFFERING OF HYDROGEN IONS IN THE BODY
- 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 major extracellular buffering system is the CO/HCO system, and the
major intracellular buffers are proteins and phosphates.
- INTEGRATION OF HOMEOSTATIC CONTROLS
- The kidneys and the respiratory system are the homeostatic regulators of plasma hydrogen-ion concentration.
- The kidneys are the ultimate balancers of body hydrogen-ion balance.
- A decrease in arterial plasma hydrogen-ion concentration causes reflex hypoventilation, which raises arterial P and, hence, raises plasma hydrogen-ion concentration toward normal. An increase in plasma hydrogen ion concentration causes reflex hyperventilation, which lowers arterial P and, hence, lowers hydrogen-ion concentration toward normal.
- RENAL MECHANISMS
- The kidneys maintain a stable plasma hydrogen-ion concentration by regulating plasma bicarbonate concentration. They can either excrete bicarbonate or contribute new bicarbonate to the blood.
- Bicarbonate is reabsorbed when hydrogen ions, generated in the tubular cells by a process catalyzed by carbonic anhydrase, are secreted into the lumen and combine with filtered bicarbonate. The secreted hydrogen ions are not excreted in this situation.
- In contrast, when the secreted hydrogen ions combine in the lumen with filtered
phosphate or other nonbicarbonate buffer, they are excreted and the kidneys
have contributed new bicarbonate to the blood.
- The kidneys also contribute new bicarbonate to the blood when they produce and excrete ammonium.
- CLASSIFICATION OF ACIDOSIS AND ALKALOSIS
- Acid-base disorders are categorized as respiratory or metabolic.
- Respiratory acidosis is due to retention of carbon dioxide, and respiratory alkalosis to excessive elimination of carbon dioxide.
- All other causes of acidosis or alkalosis are termed metabolic and reflect gain or loss, respectively, of hydrogen ions from a source other than carbon dioxide.
SECTION E: DIURETICS AND KIDNEY DISEASE
- Diuretics inhibit reabsorption of sodium and water, thereby enhancing the excretion of these substances. Different diuretics act on different nephron segments.
- Many of the symptoms of uremia (general renal malfunction) are due to retention of substances because of reduced GFR and, in the case of potassium and hydrogen ion, reduced secretion. Other symptoms are due to inadequate secretion of the renal hormones.
- Either hemodialysis or peritoneal dialysis can be used chronically to eliminate the water, ions, and waste products retained during uremia.