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Anatomy and physiology of the kidney SISTER M. ARTHUR SCHRAMM, CRNA Yankton, South Dakota The blood supply The author presents a thorough review of the kidney from both an anatomicaland physiological standpoint. Her in-depth study encompasses the kidney's reaction to various diuretic drugs. The kidneys are two organs, each weighing 125-180 gms (4-6 oz), located retroperitoneally. One is located in each lumbar area, the right slightly lower than the left, the upper pole of the right kidney resting on the 12th rib. The functional unit of the kidney is the nephron. There are approximately 1,200,000 in each kidney. The kidney has an inner layer, the medulla, the substance of which forms the 10-15 pyramids and the outer layer, cortex, in which the base of the pyramids is located. The kidney receives its blood supply from the abdominal aorta; therefore, the blood flows at a higher pressure when it reaches the capillary area than in other tissue. Blood flow enters through the renal artery (Figure 1) at the kidney hilum; it passes through the interlobar arteries of the medulla to the junction of the medulla and cortex where the flow enters the arciform arteries; the blood then passes through the interlobular arteries which tranverse the cortex. Afferent arterioles lead from these interlobular arteries to the nephrons. The afferent arteriole sub-divides into capillaries (the glomerulus), these capillaries converge to form the efferent arteriole. The efferent arteriole further sub-divides into the peritubular capillaries and the vasa recta, if the nephron is a juxtamedullary nephron. The venous blood follows a similar route of return to the renal vein and the inferior vena cava, that is: interlobular, arcuate, interlobar, vein, and vena cava. The nephron Figure 1-GrossAnatomy of the Kidney. February/1975 The nephron (Figure 2) consists of three basic parts. 1. The malpighian corpuscle, which is composed of the glomerulus surrounded by a blind pouch, Bowman's capsule. 2. The tubule to which the capsule leads, is composed of three segments: (a) the proximal convoluted tubule, about 14 mm in length, which begins in the cortex and has an outstanding brush border on the luminal side which increases surface area; (b) the loop of Ilenle, which narrows as it dips into the medulla forming descending and ascending limbs which again widen as the tubule passes through the outer medullary zone and back into the cortex (about one out of every eight loops dips deeply a number of important substances (Figure 3). The kidney's importance is appreciated when one compares cardiac output of 5.2 liters/min. for a resting 70 kg man to tissue size, function, blood flows and oxygen uptake. Figure 2-The Nephron. into the medullary area along with its corresponding capillary, the vasa recta, and is involved in the countercurrent mechanism); and (c) the distal convoluted tubule, onethird the length of the proximal tubule, which is located in the cortex. (Its initiation is associated closely with packed nuclei, called the macula densa; the brush border of the tubule is nearly absent.) 3. The collecting duct, which receives the filtrate from several distal tubules. These ducts empty into short papillary ducts of Bellini which empty into the renal calyces and thus into the renal pelvis. Figure 3-The magnitude of reabsorption by the Kidney. Processes or functions involved in urine formation Urine formation is actually a byproduct of the many important functions of the kidney. The first process is filtration, which occurs over the 1.5 square meters of capillary surface in the glomeruli of both kidneys. In comparison, a 70 kg man has a body surface of 1.73 m2 and the lung capillary surface is 70-90 m2. Yet, for the kidney size and weight, this is a very large surface. Approximately one-fourth of the cardiac output (21-25 per cent) perfuses the kidney or about 1200 ml/min. Considering the hematocrit and nourishment of the kidney, the total plasma flow through the glomeruli is about 650 ml/min. Filtration is promoted by filtration pressure differences and permeability, both of which are increased in the glomerular capillaries relative to that of skeletal muscle capillaries, but are decreased in the peritubular capillaries. This filtration per 24 hours in the kidney amounts to 170 liters of water or 1.5 liters/minute which contains Figure 4-Diagramof regionalblood flows in basal state (shaded areas)and at maximum vasodilation (unshaded areas), scaled for normaladult human subject, 70kg. Ordinate is blood flow per 100gm tissue, showing relative vascular resistance of each organ system. (From Mellander and Johansson) Tissue size in weight shows that the kidney is comparable in size to the heart, less in size than the brain, and very much smaller than the skeletal muscle or splanchnic areas. Thus, it is not for nutritive purposes that the kidney receives a large blood supply, but for plasma clearance. Blood flow in the kidney is near its full capacity, 7-8 times greater than the flow in the heart or the brain, much greater than skeletal muscle or splanchnic flow. Relative Journal of the American Association of Nurse Anesthetists Figure 5-Estimateddistribution of cardiac output and oxygen consumption in normal subjects (70kg, surface area 1. 7m 2) at rest under usual indoor conditions. (From Wade & Bishop) Figure 6-Distributionof cardiac output in normal human subjects at rest and during light, strenuous and maximal exercise that has continued for 10 min. (From Wade & Bishop) flows to muscle and heart change during exercise, and flow is not constant as it is in the brain. Oxygen uptake by heart, brain, splanchnic and skeletal muscle is in a greater amount than the kidney, even at rest. To clear the plasma does not require as high oxygen levels as does the nutritive and energy needs of the other organs. Approximately one-fourth of the cardiac output goes to the kidney, comparable only to that of skeletal muscle or splanchnic areas. This allows for adequate plasma clearance of 1200 ml per minute. Yet, under conditions of exercise, other body priorities will cause sidetracking of this amount. Glomerular filtration pressure equals the hydrostatic pressure minus the sum of colloid osmotic and capsular pressures. Glomerular hydrostatic pressure is 70 mm Hg, glomerular colloid osmotic pressure is 32 mm Hg (due to retention of protein), and capsular tissue pressure is 14 mm Hg, giving a net filtration pressure of 24 mm Hg to favor the filtration of 125 ml/min. The skeletal muscle, in comparison, has a hydrostatic pressure of 25 mm Hg. The colloid osmotic pressure is 28 mm Hg. Neg- February/1975 ative interstitial fluid pressure and colloid osmotic pressure together exert a pressure of 11.5 mm Hg, which assist the hydrostatic pressure to yield a net filtration of 8.5 mm Hg into the interstitial space in favor of cellular nutrition. On the venous side, because of a drop in capillary hydrostatic pressure, there is a net flow back into the capillary with removal of cellular wastes. Figure 7-Comparisonof Hydrostatic Pressureof Kidney to that of other tissues. The second important process is reabsorption which occurs in the proximal and distal tubules. In the peritubular capillaries, the hydrostatic pressure (Figure 7) is less than that in other tissues. This lowered pressure facilitates net filtration of substances from the tubule lumen into the capillaries, thus aiding in the reabsorption process. It is primarily in the proximal tubule that the active and passive reabsorption occurs. Figure8-Processesof the Nephron. Active reabsorption (Figure 8) which requires energy and is against a concentration gradient, includes substances such as: sodium glucose amino acids creatine phosphate sulfate uric acid potassium ascorbic acid ketones as aceto-acetic acid Beta-hydroxy-butyrate Passive absorption includes chloride and other electrolytes that are filtered, as well as the osmotically absorbed water and urea. In the proximal tubule, some of the substances such as glucose are absorbed completely if levels are physiological; sodium and water are absorbed to 80 per cent of the filtered amount, and other substances to lesser amounts. Therefore, the osmolarity of tubular fluid in the proximal tubule is still 285 mOSM, isotonic with that of plasma. The third process is secretion, (Figure 8) sometimes called tubular excretion. Secretion occurs primarily in the proximal tubule and involves such compounds as: PAH penicillin sulfonphthaleins iodinated compounds such as Diodrast®, conjugated foreign substances In the distal tubule, sodium, under the control of aldosterone, is exchanged for potassium and hydrogen ions. This area is involved in acid-base balance and electrolyte control as well as fluid balance control. Regulation of kidney function The three processes-filtration, reabsorption, and secretion-are regulated by three mechanisms. The first, autoregulation (Figure 9) affects the glomerular filtration rate (GFR) because of the control on the hydrostatic pressure of the capillaries by the afferents and the resistance of the arterioles due to vasoconstriction or dilation. Sympathetic innervation to the afferent arterioles has been demonstrated but there seems to exist an intrinsic control by which the kidney itself regulates the arteriole pressure so that the GFR is kept constant. The second, countercurrent exchange, (Figure 9) is a mechanism whereby the isotonic filtrate of the proximal tubule becomes hypertonic in the longer juxtamedullary loops as the filtrate flows down the descending loop of Henle through an increasingly hypertonic interstitium. Osmo- Figure 9-Mechanisms affecting Kidney functions. larity of the filtrate, as sodium passively flows inward and water passively flows outward to the interstitium, becomes hypertonic as the filtrate flows down descending loop. In the ascending limb, sodium is actively pumped from this ascending limb in increments back into the interstitium to replace that lost to the descending loop, this ascending limb wall is impermeable to water. By the time the filtrate returns to the cortical area, another 5 per cent of the water has been lost but relatively more sodium may have been lost. Thus, the filtrate may be diluted or reconstituted in osmolarity. The third, hormonal mechanisms (Figure 9) control sodium and water reabsorption. In the proximal distal tubule, which originates at the macula densa, the hypotonic filtrate again has the tendency to lose water and gain sodium from the isotonic cortical interstitium. The macula densa are approximate to another area of cells in the afferent arteriole; just before their entry into the glomerulus, these two structures form the juxtaglomerular apparatus. If there is a need for sodium or the afferent arteriole pressure is low, this cortical site produces renin which, indirectly through the renin-angiotensin mechanism, causes the adrenal cortex to secrete more aldosterone. This, in turn, increases sodium reabsorption and, thus, water reabsorption. In the distal tubule and collecting duct, another hormone-an antidiuretic hormone -is liberated from the post pituitary (neurohypophyseal) gland which is innervated by osmoreceptors in the hypothalamus. This hormone, also secreted by the hypothalamus, affects the permeability of the tubules to water as it again passes back through the Journal of the American Association of Nurse Anesthetists increasingly hypertonic interstitium to the ducts of Bellini. Approximately 14 per cent of the water in the filtrate is reabsorbed in this area, and the final concentration of urine occurs here. One per cent of the GFR or 1 ml/min of urine is formed. Physiological regulation in the body by the kidney A review of the many filtrate statistics and functions of the kidney reveals its great importance in body homeostasis. Besides the adjustment of electrolyte or ion concentrations, osmolarity, fluid volumes of extracellular fluid and blood, and removal of waste products and toxic substances, acidbase balance is one of interest and intrigue. The long term regulation of the pH to maintain a bicarbonate to carbonic acid ratio of 20:1 in the blood occurs primarily in the distal tubule. Here is what happens as the filtrate passes through the distal tubule. urine and carbon dioxide which is reabsorbed into the blood stream and excreted by the lungs. Figure11. In the event of acidosis, (Figure 12) more sodium is needed for exchange with hydrogen. The titratable acid Na 2HPO4 is utilized. This acid is present in the filtrate and dissociates into two sodiums and HP04-. The cellular hydrogen exchanges for one of the two sodiums. The sodium is Figure 10. The sodium of the filtrate (Figure 10) is exchanged for the hydrogen ion generated by the tubular cell metabolism. In this metabolism CO2 and H2O are produced; these form carbonic acid facilitated by the enzyme carbonic anhydrase. The carbonic acid then splits into hydrogen and bicarbonate. The hydrogen exchanges with the tubular sodium. The sodium is actively pumped into the blood stream and the cellular bicarbonate is passively reabsorbed with the sodium into the peritubular capillaries. A common exchange of hydrogen is made with the dissociated sodium from the filtrate's sodium bicarbonate. In the tubule, (Figure 11) the exchanged hydrogen and filtrate bicarbonate form carbonic acid which dissociates into water. The water, in turn, is excreted as February/1975 Figure 12. reabsorbed with the cellular bicarbonate, and the hydrogen forms NaH 2PO4 which is excreted. With increasing acidosis, (Figure 13) ammonium is formed from glutamine. Sodium chloride, which is in the filtrate, dissociates into sodium and chloride. The sodium is exchanged for the cellular hydrogen ion and is reabsorbed with the cellular bicarbonate. The hydrogen ion along with the amine NHg forms the compound ammonium (NH4 + ). Ammonium along with the chloride forms ammonium chloride which is excreted in the urine. In the state of alkalosis, the hydrogen ion may be sparse. Cellular potassium may C -+ Co U) -C. C 0) CL) N( N 0 4-4 U-1 CL) J E C N -(U 'i.U C O L 0~ 0- 0) CU 4) -Vc C E -. C C t O 0 2-0 .3 O U) ._U( - ( 4-0)* .C0a~* 4-0b v (U1 4.t UC N + ) 4-J4 CD0 C D QU C Y~ 'gyC D) _ .C _ .E cC XQ 0 IMF ~U 4 0) 0 L~(0 Q 20 (U C 0 0, C E '(5 E a, 0 0 4- E E -_ i' o' L- n dC( .1 C Duo LL 24- (U C 'C) V 8 g c O V > C c Ec c E m 0(c CC E4- _ N-V~ (U C0 3C . W I >m ~ CD 0 to2y, CCU-0 +ov MCC 0 - cvC C Ca '-' C ~C) V~ ~~0 "a . * C 44-~ C 00 CU ,O ~ C)R 0 CV 03- C H 0 O o~. 01-~ N C .O~ *ac4 0me c L 0 2 L 4 -0E . C 0V C 0( v. v C _t0 .V 0 .Q0) T) C co C" C (U DL m NXU Q c- 0) N0 U) N~4 C0( C- O2Q a U) 44 44ournal of the American Association of Nurse Anesthetists 0 (6 o C >" 0) CON C +" Co W cc Lc) - C O E O Q.C 0CO 3' O~C W CO N LU CO U WU ,N fC . cV _ 0O C. 0 U) m 4 a) O NCOC-O cu C 13) 4- 0 "E 41 V 0 O" N UCO CO O p .C a> >4-N, L~ E ECO V N+ u y C + CV0 O Evt 9 C)W C- -O CO 0) Z0Ucc CO . U ip +. )-O a) Z -'O . "C 4C =Coa CO +4 I E 0 UO EUOO oOo -d C CO E N CO OC E .) y- 8 -arE0 c N IC N .U co NCO IL CO CO C-4-' o , °_ b a)U ' D EN5 'Oi n c Es 0 CO 823~ E C a. 0 0 . 0 O.~ mg y0t .0 ac 0)) +0COCOC 0 d.0.~~O DO - 0 C.'- V c X0 Oc 0 _ Cc ) (1 U,I=c 3O ) 0)0) .+ O O 0 .c0' O aL. E~t W o COLi m 30. ~ E ~O _O C L C 2 E. U .2 . c j C CO 00 O0 w I- February/1975 4-'4-O CL' L' Z Cc vOO V F-- 0 n) co CmvO 00) CO C Co. ' exchange with sodium instead of the cellular hydrogen so as to conserve the hydrogen and allow bicarbonate excretion. Figure 13. Alteration of functions Pathology of the kidney could alter any of these mechanisms, whether it be glomerular or tubular disease. Blood pressure extremes could affect the GFR by overriding autoregulation. Drugs affecting GFR, hormones, osmolarity or electrolytes also could alter the response of these functions. An example of this alteration is found in diuretics. They can affect kidney function in five ways (Figure 14) by: 1. Increasing the blood supply to the kidney such that (a) aminophyllin causes vasodilation, (b) digitalis increases cardiac output, and (c) water intake increases plasma volume. 2. Preventing tubular reabsorption of water by use of osmotic urea, glucose, sucrose, or mannitol. 3. Preventing tubular reabsorption of. sodium or inhibiting carbonic anhydrase which interfere with chloride, bicarbonate, potassium, and water absorption and excretion. 4. Decreasing hormonal control, that is, ADH and aldosterone. 5. Decreasing production of aldosterone and cortisone by the adrenal cortex by use of drugs as metyrapone. Figure 14-Effect of Diuretics on Renal Function. Figure 15. Thus, various diuretics may have effects on fluid and electrolyte balance as well as on acid base balance. (See Table I.) Osmolarity will have some relationship to specific gravity, but the two are not directly interchangeable. Specific gravity depends on concentration and the nature of the solutes. (See Table II.) REFERENCES (1) Brobeck, J. R., ed., 1973. Best & Taylor's Physiological Basis of Medical Practice. Baltimore, Md.: Williams & Wilkins Co. Table II Correlation of specific gravity with mOSM of solute in urine SG. mOSM 1.005 1.010 1.015 1.020 1.025 1.030 1.035 1.040 200 400 600 800 1000 1200 1400 1600 Journal of the American Association of Nurse Anesthetists (2) Goodman, L. S. and Gilman, A., 1970. The Pharmacological Basis of Therapeutics. 4th ed. New York, N. Y.: Macmillan Co. (3) Goth, A., 1972. Medical Pharmacology. 6th ed. St. Louis, Mo.: C. V. Mosby Co. (4) Guyton, A. C., 1971. Textbook of Medical Physiology. Philadelphia, Pa.: Saunders. (5) Melmon, K. L. and Morrelli, H. F., 1972. Clinical Pharmacology. New York, N. Y.: Macmillian Co. (6) Mountcastle, V. B., ed., 1974. Medical Physiology. Vol. 2, 13th ed. St. Louis: C. V. Mosby Co. AUTHOR. Sister M. Arthur Schramm, CRNA, is a graduate of Sacred Heart Hospital School of Nursing and School of Anesthesia. She holds a BA degree from Mount Marty College, Yankton, South Dakota and is studying for a PhD in physiology at the University of South Dakota. She has served as instructor and director of the Sacred Heart Hospital School of Nurse Anesthesia. She is presently director of Mount Marty College School of Nurse Anesthesia in Yankton and head of the Department of Respiratory Sciences. This paper was presented at the American Association of Nurse Anesthetists 41st Annual Meeting and Clinical Session held in Chicago in August, 1974. February/1975 (7) Netter, F. H., 1973. The CIBA Collection of Medical Illustrations. CIBA Pharmaceutical Company, Division of CIBA-Geigy Corporation. (8) Pitts, R. F., 1974. Physiology of the Kidney and Bold Fluids. 3rd ed. Chicago, Ill.: Year Book Publishers, Inc. (9) Reidenberg, M., 1971. Renal Function and Drug Action. Philadelphia, Pa.: Saunders. (10) Wood-Smith, F. G., Stewart, H. C., and Vickers, M. D., 1968. Drugs in Anesthetic Practice.3rd. ed. New York, N. Y.: Appleton-Century-Crafts.