Guyton and Hall Textbook of Medical Physiology Renal Regulation PDF

CHAPTER 30 Renal Regulation of Potassium, Calcium, Phosphate, UNIT V and Magnesium; Integration of Renal Mechanisms for C...

CHAPTER 30 Renal Regulation of Potassium, Calcium, Phosphate, UNIT V and Magnesium; Integration of Renal Mechanisms for Control of Blood Volume and Extracellular Fluid Volume as a source of potassium during hypokalemia. Thus, redis- REGULATION OF EXTRACELLULAR tribution of potassium between the intracellular and FLUID POTASSIUM CONCENTRATION extracellular fluid compartments provides a first line of AND POTASSIUM EXCRETION defense against changes in extracellular fluid potassium Extracellular fluid potassium concentration normally is concentration. regulated at about 4.2 mEq/L, seldom rising or falling more than ±0.3 mEq/L. This precise control is necessary REGULATION OF INTERNAL because many cell functions are sensitive to changes in POTASSIUM DISTRIBUTION extracellular fluid potassium concentration. For instance, an increase in plasma potassium concentration of only 3 After ingestion of a normal meal, extracellular fluid potas- to 4 mEq/L can cause cardiac arrhythmias, and higher sium concentration would rise to a lethal level if the concentrations can lead to cardiac arrest or fibrillation. ingested potassium did not rapidly move into the cells. A special difficulty in regulating extracellular potas- For example, absorption of 40 mEq of potassium (the sium concentration is the fact that more than 98 percent amount contained in a meal rich in vegetables and fruit) of the total body potassium is contained in the cells into an extracellular fluid volume of 14 liters would raise and only 2 percent is contained in the extracellular fluid plasma potassium concentration by about 2.9 mEq/L if all (Figure 30-1). For a 70-kilogram adult, who has about 28 the potassium remained in the extracellular compart- liters of intracellular fluid (40 percent of body weight) and ment. Fortunately, most of the ingested potassium rapidly 14 liters of extracellular fluid (20 percent of body weight), moves into the cells until the kidneys can eliminate the about 3920 mEq of potassium are inside the cells and excess. Table 30-1 summarizes some of the factors that only about 59 mEq are in the extracellular fluid. Also, the can influence the distribution of potassium between the potassium contained in a single meal may be as high as intracellular and extracellular compartments. 50 mEq, and the daily intake usually ranges between 50 and 200 mEq/day; therefore, failure to rapidly rid the Insulin Stimulates Potassium Uptake into Cells. extracellular fluid of the ingested potassium could cause Insulin is important for increasing cell potassium uptake life-threatening hyperkalemia (increased plasma potas- after a meal. In people who have insulin deficiency owing sium concentration). Likewise, a small loss of potassium to diabetes mellitus, the rise in plasma potassium concen- from the extracellular fluid could cause severe hypokale- tration after eating a meal is much greater than normal. mia (low plasma potassium concentration) in the absence Injections of insulin, however, can help to correct the of rapid and appropriate compensatory responses. hyperkalemia. Maintenance of balance between intake and output of potassium depends primarily on excretion by the kidneys Aldosterone Increases Potassium Uptake into Cells. because the amount excreted in the feces is only about 5 Increased potassium intake also stimulates secretion of to 10 percent of the potassium intake. Thus, the mainte- aldosterone, which increases cell potassium uptake. Excess nance of normal potassium balance requires the kidneys aldosterone secretion (Conn’s syndrome) is almost invari- to adjust their potassium excretion rapidly and precisely ably associated with hypokalemia, due in part to move- in response to wide variations in intake, as is also true for ment of extracellular potassium into the cells. Conversely, most other electrolytes. patients with deficient aldosterone production (Addison’s Control of potassium distribution between the extra- disease) often have clinically significant hyperkalemia due cellular and intracellular compartments also plays an to accumulation of potassium in the extracellular space, important role in potassium homeostasis. Because more as well as renal retention of potassium. than 98 percent of the total body potassium is contained in the cells, they can serve as an overflow site for excess β-Adrenergic Stimulation Increases Cellular Uptake extracellular fluid potassium during hyperkalemia or of Potassium. Increased secretion of catecholamines, 389 Unit V The Body Fluids and Kidneys K+ intake Cell Lysis Causes Increased Extracellular Potassium 100 mEq/day Concentration. As cells are destroyed, the large amounts of potassium contained in the cells are released into the Extracellular Intracellular extracellular compartment. This release of potassium can fluid K+ fluid K+ cause significant hyperkalemia if large amounts of tissue 4.2 mEq/L 140 mEq/L are destroyed, as occurs with severe muscle injury or with × 14 L × 28 L red blood cell lysis. Strenuous Exercise Can Cause Hyperkalemia by 59 mEq 3920 mEq Releasing Potassium from Skeletal Muscle. During prolonged exercise, potassium is released from skeletal K+ output Urine 92 mEq/day muscle into the extracellular fluid. Usually the hyperkale- Feces 8 mEq/day mia is mild, but it may be clinically significant after heavy 100 mEq/day exercise, especially in patients treated with β-adrenergic Figure 30-1. Normal potassium intake, distribution of potassium in blockers or in individuals with insulin deficiency. In rare the body fluids, and potassium output from the body. instances, hyperkalemia after exercise may be severe enough to cause cardiac toxicity. Table 30-1 Factors That Can Alter Potassium Distribution Between the Intracellular and Increased Extracellular Fluid Osmolarity Causes Extracellular Fluid Redistribution of Potassium from the Cells to Extracellular Fluid. Increased extracellular fluid osmo- Factors That Shift K+ Factors That Shift K+ larity causes osmotic flow of water out of the cells. The Into Cells (Decrease Out of Cells (Increase Extracellular [K+]) Extracellular [K+]) cellular dehydration increases intracellular potassium concentration, thereby promoting diffusion of potassium Insulin Insulin deficiency (diabetes mellitus) out of the cells and increasing extracellular fluid potas- sium concentration. Decreased extracellular fluid osmo- Aldosterone Aldosterone deficiency (Addison’s disease) larity has the opposite effect. β-adrenergic stimulation β-adrenergic blockade Alkalosis Acidosis OVERVIEW OF RENAL POTASSIUM EXCRETION Cell lysis Renal potassium excretion is determined by the sum Strenuous exercise of three processes: (1) the rate of potassium filtration Increased extracellular fluid (glomerular filtration rate [GFR] multiplied by the plasma osmolarity potassium concentration), (2) the rate of potassium reab- sorption by the tubules, and (3) the rate of potassium secretion by the tubules. The normal rate of potassium especially epinephrine, can cause movement of potas- filtration by the glomerular capillaries is about 756 mEq/ sium from the extracellular to the intracellular fluid, day (GFR, 180 L/day multiplied by plasma potassium mainly by activation of β2-adrenergic receptors. Con­ concentration, 4.2 mEq/L). This rate of filtration is rela- versely, treatment of hypertension with β-adrenergic tively constant in healthy persons because of the auto- receptor blockers, such as propranolol, causes potassium regulatory mechanisms for GFR discussed previously and to move out of the cells and creates a tendency toward the precision with which plasma potassium concentration hyperkalemia. is regulated. Severe decreases in GFR in certain renal diseases, however, can cause serious potassium accumu- Acid-Base Abnormalities Can Cause Changes in lation and hyperkalemia. Potassium Distribution. Metabolic acidosis increases Figure 30-2 summarizes the tubular handling of extracellular potassium concentration, in part by causing potassium under normal conditions. About 65 percent of loss of potassium from the cells, whereas metabolic alka- the filtered potassium is reabsorbed in the proximal losis decreases extracellular fluid potassium concentra- tubule. Another 25 to 30 percent of the filtered potassium tion. Although the mechanisms responsible for the effect is reabsorbed in the loop of Henle, especially in the thick of hydrogen ion concentration on potassium internal dis- ascending part where potassium is actively co-transported tribution are not completely understood, one effect of along with sodium and chloride. In both the proximal increased hydrogen ion concentration is to reduce the tubule and the loop of Henle, a relatively constant fraction activity of the sodium-potassium adenosine triphospha- of the filtered potassium load is reabsorbed. Changes in tase (ATPase) pump. This reduction in turn decreases potassium reabsorption in these segments can influence cellular uptake of potassium and raises extracellular potassium excretion, but most of the day-to-day variation potassium concentration. of potassium excretion is not due to changes in 390  Chapter 30 Renal Regulation of Potassium, Calcium, Phosphate, and Magnesium 65% 8% Renal Principal Tubular (491 mEq/day) (60 mEq/day) interstitial cells lumen 756 mEq/day fluid (180 L/day × 4.2 mEq/L) Na+ ENaC Na+ UNIT V Na+ 27% ATP (204 mEq/day) K+ K+ BK K+ K+ ROMK 4% 0 mV –70 mV –50 mV (30 mEq/day) Figure 30-3. Mechanisms of potassium secretion and sodium reab­ sorption by the principal cells of the late distal and collecting tubules. BK, “big” potassium channel; ENaC, epithelial sodium channel; ROMK, renal outer medullary potassium channel. 12% (92 mEq/day) Figure 30-2. Renal tubular sites of potassium reabsorption and When potassium intake is low, secretion of potassium secretion. Potassium is reabsorbed in the proximal tubule and in the in the distal and collecting tubules decreases, causing a ascending loop of Henle, so only about 8 percent of the filtered load reduction in urinary potassium excretion. There is also is delivered to the distal tubule. Secretion of potassium by the prin­ increased reabsorption of potassium by the intercalated cipal cells of the late distal tubules and collecting ducts adds to the cells in the distal segments of the nephron, and potassium amount delivered, but there is some additional reabsorption by the intercalated cells; therefore, the daily excretion is about 12 percent excretion can fall to less than 1 percent of the potassium of the potassium filtered at the glomerular capillaries. The percent­ in the glomerular filtrate (to