Composition of Renal Medullary Tissue
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CORE Metadata, citation and similar papers at core.ac.uk Provided by Elsevier - Publisher Connector Kidney International, Vol. 31(1987), pp. 556—561 Composition of renal medullary tissue RUTH ELLEN BULGER Renal Research Laboratory, University of Texas Health Science Center at Houston, Graduate School of Biomedical Sciences, Houston, Texas, USA Concentration of the urine is achieved by osmotic equilibriumtissue chloride concentration in rabbit medullary tissue when of the collecting duct fluid with the hypertonic, medullarycompared to that of the cortex. Investigators soon realized that interstitial fluid. The medullary tissue concentration of variousthere were problems in expressing their determinations using osmotically—active substances, especially urea and sodiumthe most appropriate reference standard, since both overall chloride, undergoes drastic changes depending on the physio-solute and water content were changing. Results are still logical state of the animal. It has been assumed that intracellularexpressed in a variety of units, which only rarely use DNA or and extracellular osmotic pressures and urea concentrations areprotein as a reference standard. In addition, the physiological equal. However, many questions remain unanswered. What arestate of the renal medulla varies with enormous changes in urine the concentrations of osmotically active molecules in each ofosmolality (and hence of the various solutes and amount of the various compartments? What types and amounts of smallwater present). One might therefore expect to find large differ- organic compounds are present? How does the high osmolalityences in salts and water in the medulla which correlate with the effect the metabolic state of these cells? Are inorganic mole-physiological state of the animal studied. cules bound, that is, what are their activity coefficients? Another problem inherent in the chemical analyses is the Many techniques have been used to approach these questionslarge quantity of fluid in the lumens of the renal medulla, which including chemical analysis of whole slices of tissue, freez-may contain fluid with greatly differing concentrations of dif- ing—point depression studies of tissue slices, microcentrifuga-fusible ions from that in the surrounding tissue (for example low tion to obtain interstitial fluid, micropuncture of the tubules andsodium in the collecting tubule). Some preservation techniques capillaries at various levels within the renal medulla, cell(rapid freezing) retain this fluid within the lumens while other isolation and culture techniques, and electron microprobe anal-techniques do not. ysis. In this paper, values for the concentration and content of In spite of these problems, general trends were established. solute and water in various physiological states will be reviewedUllrich and coworkers [17, 18, 20] showed that in antidiuresis, with emphasis on the results obtained from electron microprobethe content of sodium, chloride, urea and creatinine of the dog analysis. papilla increased, while that of potassium, magnesium, calcium, In 1908 Hirokawa [1] observed that the osmotic pressure ofand phosphorus did not. The tissue concentration of solutes the renal medulla was extraordinarily variable but the value wasalso increased and reflected the increased concentration of always higher than in the renal cortex. He also noted that theurine. The osmotic pressure at the papillary tip was, in fact, osmotic pressure of the urine increased during passage throughfound to be the same as that of the final urine. In addition, these the loops of Henle and the collecting tubules. Kuhn and Ryffelauthors showed that approximately 75 to 80% of the increased [2] proposed that the loops of Henle functioned as a counter-osmolality in the medullary tissue was accounted for by sodium current multiplier. Using frozen sections, 30 m thick, of ratchloride and urea. During diuresis, a decrease in papillary kidney, mounted between cover glasses in a bath whose tem-osmolality was noted. Gardner and Vierling [9] showed that perature was gradually raised, Wirz, Hargitay, and Kuhn [3]papillary content of all solids, and specifically sodium and urea, measured the melting point to determine the osmotic pressureincreased with increasing urinary concentration, but water, of the tubular contents. They demonstrated that the osmoticDNA, and protein content did not change. They noted that large pressure of the luminal contents rose from the cortico-medul-increases in tissue urea as occurs in antidiuresis (up to 20% of lary boundary to the papillary tip. medullary dry weight), complicate the terminology for expres- Analysis of medullary tissue by several investigators pro-sion of content, and suggested the use of urea—free dry weight. vided the first chemical determinations of the contents ofBray 121], Dicker [22], and Ruiz—Guinazu, Arrizurieta and medulla in diuretic and antidiuretic states [4—19] (Table 1). InYelinek [23] all demonstrated that the osmolality of the medulla most of these studies, the sodium and urea concentrations rosedecreased during water diuresis but remained hypertonic to the progressively from the cortico-medullary junction toward the plasma. papilla. Ljungberg [13], demonstrated a sevenfold increase in Careful studies of the content and concentration of the renal medulla at various stages after antidiuretic hormone (ADH) administration were useful in attempts to understand the tem- Received for publication July 9, 1986 poral effects of ADH [4—8, 10—12, 14, 15, 17]. In a chemical ©1987 by the International Society of Nephrology analysis of kidney pieces by Schmidt—Nielsen, Graves and Roth 556 Inorganic content of medulla 557 Table 1. Composition of urine, renal papilla, and cortex Urine Papilla Cortex mMoles/KgH2O mMoles/KgH2O mMoles/KgH2O Reference Dog Water diuresis Osmolality 70.6 16.6 [12] Na 2.8 2.5 118 23.1 68.1 5.7 5,8 3.7 48.6 4.4 77.2 4.0 Urea 42.1 16.4 33.4 9.1 10.0 2.5 2 hr post-ADH administration Osmolality 1012 232 [12] Na 148 34.4 206 27.5 80.5 5.4 120 75.6 45.6 6.1 13.4 3.9 Dehydration Osmolality 1725 361 [12] Na 153 60 320 48.4 80.8 8.9 162 70 52.7 5.5 80.5 7.9 Urea 991 228 855 160 21.0 4.6 Rat Hydropenia Osmolality 2275 253 [15] Na 76 30 470 148 898 K 178 33 175 56 98 8 Urea 1500 175 871 264 22 4 Water diuresis Osmolality 172 95 [15] Na 3.4 2.1 312 71 89 14 11.8 5.4 190 62 92 14 Urea 137 70 177 89 22 6 Normal Osmolality 2056 [19] Na 181.1 8.8 358.4 33.2 79.2 2.8 K 356.7 22.7 43.2 4.3 93.9 1.7 Urea 839.3 56.9 583.5 47.9 18.0 5.4 Diabetes insipidus Osmolality 124.0 6.7 [19] Na 9.9 1.1 201.5 31.0 89.5 3.0 18.2 1.4 39.6 8.2 93.9 4.3 Urea 59.6 5.2 40.7 18.4 6.3 3.8 Diabetes insipidus treated with ADH Osmolality 969.0 220.2 [19] Na 84.5 11.4 236.8 36.1 81.6 4.0 K 150.3 33.0 41.5 3.1 90.4 3.6 Urea 479.6 126 282.8 57.3 16.9 6.5 Dehydration Osmolality 3817.0 89.3 [19] Na 247.8 26.4 401.8 26.9 80.9 3.9 K 438.2 24.9 53.9 4.9 90.1 3.8 Urea 2172.0 65.5 811.8 18.3 18.5 2.8 [24], the two most important factors contributing to the rise invarying their sodium content. This finding agreed with the inner medullary osmolality were removal of water and additionearlier results of Ullrich and Pehling [26] who found that the of urea. The addition of urea to the papillary tissue exceededsodium space of the inner medulla approximated the total the contribution of the osmotic equivalent of sodium chloridevolume of the tissue. by a factor of 2.8 in both rats and hamsters. Because a relatively large piece of renal medulla is required Morgan [25] bisected the renal papilla and incubated it infor chemical analysis, small areas of renal medulla cannot be media in which sodium chloride was varied from 150 to 600 mrvistudied. In addition, no direct way to analyze and compare the and potassium chloride was varied from 2 to 20 m. Thecomposition of cellular versus extracellular compartments was increase in sodium chloride to 600 m reduced cell volume byavailable. Therefore, techniques with higher spatial resolution 25%, increased cell sodium content by 250%, but had nowere necessary. significant effect on cell potassium concentration or content. The concentrations of various inorganic substances in spe- Increasing the potassium in the media did not change cell watercific locations within the renal medulla have been determined or sodiuni, but did increase cell potassium. Morgan [25] con-using micropuncture and microanalytical techniques by many cluded that papillary cells maintain osmotic equilibrium byinvestigators. For example, Wirz [27] demonstrated that blood 558 Bulger Table 2. Analysis of urine in papillary interstitial fluid from diabetes constant intracellular potassium is of considerable importance insipidus rats [34] considering the sensitivity of intracellular enzymes to potas- Papillaryinterstitial sium concentration [24]. Recent x-ray microprobe studies (Ta- fluid Urine bles 3 and 4) also disclose constant intracellular potassium mmolelliter mmole/liter value. It therefore appears that cellular potassium levels are (means SD) (means SD) reasonably constant throughout the cortex and medulla, and do Na Urea Na Urea not play an important role in the response of the cells to the hyperosmolality of the medulla. Untreated, heterozygous288 61380 123201 28533 48 hr. dehydration heterozygous 486 74810 127298 731469 301 Electron microprobe analysis Untreated, homozygous169 4672 14 25 5 75 103 Electron microprobe analysis has the potential to allow 14 hr dehydration measurements of total solids (mass), and mass fractions of homozygous 179 23284 10322 7414 77 various elements (from which concentrations can be calculated Post-ADH homozygous 231 34347 159170 50495 193 if water content is known) within each cellular and extracellular compartment of the renal medulla.