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Rom J Leg Med [22] 199-208 [2014] DOI: 10.4323/rjlm.2014.199 © 2014 Romanian Society of Legal Medicine

The significance of reciprocal induction relations between the derivates of nephrogenic . Implications in pathology and

Gheorghe S. Dragoi1,*, Petru Razvan Melinte2, Ileana Dinca2, Elena Patrascu2, Serban A. Dragoi3

______Abstract: Functional capacity of renal excretory biosystem is assured by remarkable complex structures: glomerular basal membrane for of plasma, tubular system of the for resorption-secretion processes and juxtaglomerular complex for self-balancing.The purpose of the paper is to draw the attention of histopathologists over the phenotypic transformation of metanephrogen and over the relations between derivates of this mesenchyme in the ontogenesis process, with implications in pathology and regeneration. Authors conducted this study and, by classical microanatomic methods, they highlighted the structural heterogeneity of renal , the phenotypic variability of glomerular network, the spatial distribution and the relations of intraglomerular mesangial matrix Based on personal observations, authors notice the fact that only a proper acknowledgement of reciprocal induction relations consequences between ureteric bud emerged from and metanephrogenic blastema allows the understanding of renal structural particularities and the determinant factors in anatomical-functional disposition of renal excretory biosystem, as well as the implications in pathology and regeneration. Key Words: nephron, renal , metanephrogenic mesenchyme, ureteric bud, reciprocal induction, stem cells.

he functional structures of renal excretory nephrogenic mesoderm? Tsystem are determined during ontogenesis by What are the determining factors for the competence the phenotype changes of metanephrogen mesenchyme, of metanephrogenic mesenchyme to specifically respond to the in the presence of reciprocal induction relations between inductive action of ureteral bud derived from mesonephros the derivates of nephrogenic mesoderm (Mesoderma mesenchyme? intermedium). The structural heterogeneity of renal What are the topographic, anatomic and functional parenchyma and the phenotype variability of its elements relations between the derivates of metanephrogenic raised many problems regarding their genesis and evolution: mesenchyme? How is achieved the formation of many structural What are the necessary and sufficient conditions elements of renal parenchyma from the mesenchyme of for the phenotype differentiation of the elements of nephrogenic mesoderm that is initially a homogenous metanephrogenic mesenchyme into the endothelial, epithelial structure?; and mesangial structures? Is it possible that the elements of renal parenchyma Are there any stem cells present inside completely have another origin beside primordial mesenchyme of differentiated renal parenchyma and what is their location?

1) Romanian Academy of Medical Sciences, Bucharest, Romania * Corresponding author: Prof.MD, PhD, E-mail [email protected] 2) University of Medicine and Pharmacy of Craiova, Department of , Craiova, Romania 3) Division of Nephrology and , Georgetown University, Washington DC, 20007,USA

199 Dragoi G.S. et al The significance of reciprocal induction relations between the derivates of nephrogenic mesoderm

Is there a genetic control over the phenotype changes walls of the capsular space belong to proximal convoluted undergone by metanephrogenic mesenchyme? tube derived from metanephrogenic mesenchyme after What is the practical importance for the knowledge tubule-genesis processes. The glomerular capillary network of relations between the derivates of metanephrogenic is also derived from metanephrogenic mesenchyme after mesenchyme in pathomorphgenesis and/or in nosologic processes, offering a structural autonomy classification of elementary renal lesions? to renal glomerulus. Between the two derivates from We proposed ourselves to perform a microanatomic metanephrogenic mesenchyme establish contiguity relations analysis of the relations between the derivates of after the adhesion of internal wall of capsular space to the metanephrogenic mesenchyme, that is necessary for the glomerular arterial network. Thus, the anatomic rigorous evaluation in optic microscopy of the structures and functional unit of glomerular filtration is formed; it is involved in filtration, resorption and secretion inside known as basal glomerular membrane (membrana basalis) renal . The purpose of the paper is to that also includes intraglomerular mesangium. draw the attention on the phenotype changes undergone d. Mesangium forms a glomerular stroma and is by metanephrogenic mesenchyme and on the relations a supportive structure for glomerular arterial capillaries. between the derivate of this mesenchyme during ontogenesis In the structure of mesangium we find mesangial dynamics; we also deal with their implications in pathology cells (Mesangiocytus) and a mesangial matrix (Matrix and regeneration processes. mesangialis) that play important roles in the regulation of Problems raised by semantic content and use of blood flow and glomerular filtration. terms in the structural anatomy of renal parenchyma. There e. Nephrogenic mesoderm, known as mesoderma are numerous difficulties in understanding the anatomic intermedium, contains mesenchyme that will form the descriptions in some books, due to the confusing semantic nephrogenic chord that will metameric segment and content of terms or their wrong use while nominating achieve two ephemeral structures in the superior and different structures. The international homologation of middle parts of : and mesonephros. At the terms used in the description of renal parenchyma the caudal part of embryo, still remains a non-segmented was achieved on the following organization levels: macro- sector from the nephrogenic chord – metanephros. anatomic, micro-anatomic and embryologic. The terms that By metanephrogenic bud (Massa metanephrogenica, nominate anatomic structures involved in time and space Metanephrogenic blastema), metanephros will contribute to progress of renal functions such as filtration, resorption the formation of definitive kidney after reciprocal induction and secretion, still need to the emphasized: nephronum, to ureteral bud (Diverticulum metanephricum) developed corpusculum renale, glomerulus, mesangium, mesoderma from Wolff canal [6]. The absence of ureteral bud lead to intermedium, mesonephros, metanephros, induction, the non-differentiation of metanephrogenic blastemal and vasculogenesis. consequently to renal agenesis. a. Nephron (Nephronum) is an anatomic and f. Induction is a process involved in ; functional system made of (corpusculum an embryonic region interacts with another region in order to renale) and tubular subsystem (tubulus renalis). The influence its differentiation or behavior. There are two types collecting (ductus colligen) and papillary duct (Ductus of induction: 1. Primary embryonic induction that is at the papillaris) are not parts of nephron Histologic Terminology basis of the formation of embryo dorsal axis; 2. Secondary (2008) incorporate them [1]. induction – a group of cells respond to the action of another b. Renal corpuscle (Corpusculum renale) is a group of cells (example: -mesenchyme); it has a subsystem of nephron, made of renal glomerulus discovered regional and genetic specificity. by Malpighi (1666) [2] and glomerular capsule (capsula g. Vasculogenesis is the process of glomerularis) described by Bowman (1842) [3]. formation that take place by the production “de novo” c. Renal glomerulus (glomerulus) is the structural of endothelial cells. It takes place during the embryonic unit of renal corpuscle and it is made of arterial blood development of blood vessels and during tumor growing capillaries (Vas capillare glomerulare) that form the in adults. Another process of blood vessels formation is glomerular capillary network (Rete capillare glomerulare) that is different from vasculogenesis and and intraglomerular mesangium located in the spaces consists of the burgeoning of preexistent vessels. between capillaries. The term of renal glomerulus is frequently used as a synonym to renal corpuscle. But MATERIALS AND METHODS facts related to vasculogenesis and tubule-genesis plead against it. Because of the contiguity relations that establish The microanatomic study of the effects generated between the metanephrogenic mesenchyme derivates by reciprocal induction processes between the structures – glomerular arterial capillaries network and proximal of nephrogenic mesoderm, was achieved on fragments of convoluted tube – there is a capsular space (Spatium kidney harvested from three seven months old fetuses, from capsulare; Spatium urinarium) limited by an external wall adults aged 25 and 35 years old and from three aged made of epithelial cells (Epitheliocytus parietalis) and an 8 weeks old. The fragments were fixed in 8% formaldehyde internal wall made of capsular visceral cells (Podocytus; solution buffered at pH 7.2 and then embedded in paraffin Visceral cell of capsule). One can easily notice that the using classical methods. 5 microns serried sections were

200 Romanian Journal of Legal Medicine Vol. XXII, No 3(2014) stained with Hematoxiline Eosine for general topographic form the arcuate , with arcuate trajectory at the basis orientation and MacManus Periodic Acid Schiff stain for the of pyramids (Fig. 1). On seriate sections of renal fragments visualization of PAS positive neutral mucopolysaccharides. injected with China ink, the presence of Four fetus, new born and adult kidneys were injected intra- located along Ferrein pyramids is easily noticeable (Fig. 1 arterial with China ink to study the anatomic and structural and 3A). They form the afferent arteries of renal glomeruli variability of capillary networks and glomerular loops. (Fig. 3 A-D). The angles under which these arteriolas The sections were examined using Nikon Eclipse detach from interlobular arteries are variables: sharp angle 80i research microscope. The images were captured by with medial opening in its inferior third, right angle in the Nikon Digital Sight DS-Fi1 High Definition Color Camera middle third and sharp angle with lateral opening in the Head, using Nis Element Basic Research software. Photos superior third, underneath fibrous capsule. Glomerular were processed in Adobe Photoshop CS5 software. afferent arteriolas, after a short path, spread in order to form a plexiform capillary network (Fig. 3 G-O). Between RESULTS glomerular blood vessels, it is noticed the presence of various spaces of intraglomerular mesangial location (Fig. The study of relations between derivates of 3 I-O).When examining with 40X and 60X objectives, we nephrogenic mesoderm (Mesoderma intermedium) was visualized glomerular blood with sinusoidal trajectory and achieved through: microanatomic analysis of structures through their connection to the efferent , they location within renal cortical, analysis of glomerular form vascular loops (ansa) (Fig. 3 I-M) which branch off capillary networks phenotypic variability and the analysis extraglomerular, achieving an important capillary network of distribution and relations of intraglomerular mesangial around convoluted tubules and Henle loop (Fig. 3 B, C, E,F). matrix. C. Analysis of spatial distribution and relations of A. Microanatomic analysis of intraglomerular mesangial matrix The study was performed on seriate sections, When examining with the 40X and 60X objectives in frontal plane, through kidneys obtained from Homo the seriate sections of renal cortex stained/coloured with Sapiens fetuses, aged 7 months and through metanephros of Mac Mannus Periodic Acid Schiff stain, we identified 8 weeks embryo. When examining with the 4X objective, we the presence of PAS-positive material, both at the level of identified the cortical (Cortex renalis), medullar ( parietal sheet of glomerular capsule, as well as the level renalis) and columnar (Columna renalis) regions of renal of glomerular capillary networks (Fig. 4). Capillaries of parenchyma, as well as sectors of cortical region (Labyrintus glomerular network, grouped inside lobules, are sectionated corticis with Cortex corticis, Radius medullaris and under various angles and delineated by PAS-positive Lobulus corticalis) (Fig. 1). When examining with the 10X subendothelial membrane, with circumferential trajectory. and 20X objectives, within cortex corticis, we noticed the The geometrical shape of glomerular arterial capillaries fibrous capsule of the kidney (Capsula fibrosa), “spheroid” depends on the sectional plane: transverse, oblique or shaped condensations of metanephrogenic mesenchyme longitudinal. Within the dihedral angle determined by two (Massa metanephrogenica) which contribute to the planes that contain capillaries, we visualized a remarkable formation of nephrovascular (Glomerulus) and secretory accumulation of PAS-positive, neutral mucopolysaccharides, nephrotubular (Tubulus secretorius) structures. (Fig. 2 A, in contiguity relations with subepithelial basal membranes B).The examination with 20X and 40X objectives allowed of peripheral capillaries (Fig. 4 A/D; I J). This distribution the visualization of renal glomerular capsular primordium, of mucopolysaccharides determines the aspect of “angular as structural part of proximal tubular system that, within mesangium”. When examining longitudinal sections from spaces, has the shape of italic “S” letter. (Fig. 2 B, C).From glomerular vascular lobules, it is easily noticeable the the analysis of seriate sections, we noticed the volumetric presence of PAS-positive mesangial matrix within the space increase of glomerular primordium, by two simultaneous between two arteriolar capillaries that determine a radial processes: numeric increase of blood capillaries by spatial distribution ( Fig. 4 K-N). vasculogenesis process, the differentiation of mesangial cells and matrix on one side and the phenotypic transformation DISCUSSIONS of glomerular capsule visceral layers cells into , on the other side. (Fig. 2 F-H). Evolution in time and space of nephrogenic B. Analysis of glomerular capillary networks mesoderm mesenchyme determines the appearance of phenotypic variability two fundamental structures which represent the basis of The study of phenotypic variability of arterial renal parenchyma morphogenesis: ureteric bud, developed glomerular capillary network was achieved on seriate within the inferior extremity of mesonephrotic duct and sections through 7 months fetus kidney, new born and metanephrogenic blastema (Masa metanephrogenica), adult, with and without injecting chromatic tracer (China differentiated from caudal extremity of nephrogenic cord. ink). When examining with the 4X objective, we identified The acknowledgement of reciprocal induction relations the within Bertin columns, which have between ureteric bud and metanephrogenic blastema parallel trajectory with longitudinal axis of renal pyramids. allows the understanding of renal parenchyma structural At the level of renal pyramids’ basis, they divide in order to particularities and of determinant factors in anatomical-

201 Dragoi G.S. et al The significance of reciprocal induction relations between the derivates of nephrogenic mesoderm

Figure 1. Structural heterogeneity of renal cortex in a 7 months old human fetus. Underneath the “fibrous capsule”, in “cortex corticis” area, one can visualize subcapsular nephron primordia that differentiate from metanephros mesenchyme by phenotype changes. 1. Fibrous capsule; 2. Cortex corticis; 3. Labyrinthus corticis; 4. Radii medulares (Ferrein); 5. Arcuate ; 6. Pyramis renalis. Paraffin section. Hematoxyline Eosine stain. Micro-photos taken by Digital Sight DS-Fi1 High Definition Color Camera Head. X28.

202 Romanian Journal of Legal Medicine Vol. XXII, No 3(2014)

Figure 2. Sequential imagery for the morphogenesis of structural elements forming renal corpuscle inside metanephros mesenchyme by vasculogenesis (glomerulus) and tubule genesis processes (capsula glomerularis). 1. Fibrous capsule; 2. Cortex corticis; 3. Metanephros mass; 4. Primordia of proximal convoluted tube and of glomerulus; 5. Nephron loop; 6. Tubulus proximalis; 7. Capsula glomerularis – stratum viscerale; 8. Capsula glomerularis – stratum parietale; 9. Primordia for renal glomerulus; 10. Capsular space; 11. Rete capsulare glomerulare.Paraffin section. Hematoxyline Eosine stain. Micro-photos taken by Digital Sight DS- Fi1 High Definition Color Camera Head. x70 (A); x140 (B-D); x280 (E, H); x420 (F, G).

203 Dragoi G.S. et al The significance of reciprocal induction relations between the derivates of nephrogenic mesoderm

Figure 3. The variable shape of renal glomerulus, the variable angles of afferent arteries branching from interlobular arteries, the variable trajectory of capillaries and capillary networks around tubules. 1. Glomerulus; 2. Interlobular artery; 3. Peritubular capillary plexus; 4. Arteriola glomerulus afferens; 5. Capillary blood vessel inside glomerulus; 6. Glomerular intercapillary space. Paraffin section. Intra-arterial injection with China ink. Micro-photos taken by Digital Sight D - Fi1 High Definition Color Camera Head. x70 (A); x140 (B-D); x280 (E, H); x420 (F, G).

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Figure 4. Location and relations of PAS positive “matrix mesangialis” inside renal glomerulus and glomerular capsule. It is located inside the spaces between glomerular arterial capillaries near glomerular basal membrane. 1. Capsula glomerularis – stratum parietale; 2. Spatium capsulare; 3. Rete capillare glomerulare; 4. Glomerular capillary blood vessel; 5. Matrix mesangialis; 6. Vascular pole.Paraffin section. MacManus stain. Micro-photos taken by Digital Sight DS-Fi1 High Definition Color Camera Head. x140 (A, C, D, F); x280 (G-L); x420 (M, N).

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Table 1. Contribution to the knowledge of renal glomerulus structures and its homologation International Anatomical Authors English Terms Terminology Eponyms

(1666) Renal pyramid Pyramid renalis Malpighi pyramids (1628-1694) [2] Glomerulus (1666) Malpighi corpuscul Antoine Ferrein (1693-1769)[4] Renal Radius medullaris Ferrein’s pyramids Exupere Joseph Bertin (1712-1781) [5] Columna renalis Bertin’s columns Gospar Friedrich Wolff Ductus mesonephricus Wolffian duct (1735-1794) [6] Mesonephros (1759) Mesonephros Wolffian body Capsule glomerularis Sir William Bowman Glomerular capsule (1842) Bowman’s capsule (1816-1892) [3] Spatium capsulare (Spatium Capsular space (Urinary space) urinarium) Bowman’s space Karl Wilhelm Zimmermann Connective for supports glomerular Mesangium (1861-1935) [7] capillaries (1933) (Mesangium) - Juxtaglomerular apparatus (Juxtaglomerular Goormaghtigh’s (1932) Complexus juxtaglomerularis Juxtaglomerular complex) apparatus 1. (1929) 1. Macula densa Camillo Golgi (1889) a. Epithelial cell of macula densa a. Epitheliocylus maculae densa (1843-1926) [8] K.W. Zimmermann (1929) 2. arteriolarum [7] 2. Glomerular tunica of arteriole glomerularum J.H. Ruyter (1925) [9] a. Juxtaglomerular epitheloid cell (Granular cell) a. Juxtaglomerulocytus Charles Oberling (1927) (Myocytus juxtaglomerularis) (1895-1960) [10] Norbert Goormaghtigh 3. Perivascular islet of mesangial cell (1890-1960) [11] Sin: - extraglomerular mesangium Zimmermann’s - Polar cushion 3. Insula perivascularis mesangii polkisen - Laces a. Mesangiocytus - Polkissen extraglomerularis Goormaghtigh’s a. Extraglomerular mesangial cell (Lacis, cell Agranular cell) functional disposition of renal excretory biosystem. 1987 [15]; Coffin et al., 1991 [16]; Hyink et al., 1996 [17]). The study of microanatomic relations between Researches on culture organs and interspecies transplant the derivates of nephrognic mesoderma mesenchyme experiments demonstrated the extrarenal origin of determines the expansion of anatomical researches in the area renal glomerular endothelial cells, through angiogenesis of nephron’s structures morphogenesis and mostly of blood mechanism (Saxen 1987 [15]; Pinson et al. 1995 [18]; Berstein vessels genesis from renal glomerular capillary network. Our et al. 1981 [19]; Ekblom et al. 1982 [20]; Sariola et al. 1983 study, achieved through classical microanatomic methods [21]). Although, studies of transgenic mice experiments highlighted the structural heterogeneity of renal cortex, suggested that glomerular develops through the phenotypic variability of glomerular capillary network, vasculogenesis (Hyink et al., 1996 [17]; Potter, 1965 [22]; the spatial distribution and the relations of intraglomerular Robert et al., 1996 [23]; Abrahamson et al., 1998 [24]). The mesangial matrix. presence of angioblasts, materialized by Flt-1 and Flk-1 in Felix (1912) [12] stated that, in order to prevascular metanephrogenic blastema sustains the idea understand the structural anatomy of renal glomerulus, the of vasculogenesis contribution to the development of renal morphogenesis of glomerular capillary network most be blood vessels. The cells of metanephrogenic mesenchyme known. The origin of renal parenchyma blood vessels was (Metanephritic mesenchimal cell) migrated within the highly controversial. Sabin (1917) [13] promoted the idea of depression of proximal convoluted tubule, through vascular renal vessels development direct from mesoderm through genesis, can organize the glomerular capillary network. burgeoning (angiogenesis). Edward (1951) [14] described This is achieved by the coalescence, , of endothelial terminal buds of branches which grow and precursory cells (endothelial precursor cells; synonym: occupy Bowmann capsule , where they form angioblasts) and then by connection to large vessels (Risau glomerular capillary network. and Flamme, 1995) [25]. Nowadays, it is considered that the evolution Molecullar basis of genesis and the organization of metanephrogenic mesenchyme is determined by the of renal vascularization are unknown. Still, the role of interactions between ureteric bud and metanephrogenic angiogenic factors was accepted (Saxen, 1987 [15]; Kloth blastema. The simultaneous development of renal blood et al., 1995 [26]). The presence of angioblasts with FlK1 vessels and differentiation of nephrotubular structures and FPt1 within metanephrogenic blastema suggests epithelium through vasculogenesis (differentiation in situ, that the vasculogenesis is involved in the development of from angioblasts) and/or angiogenesis (sprouting from renal vessels. In tissular metanephros cultures, the VEGF the preexisting vessels) has been demonstrated (Saxen, manifestation is weak. The addition of rhVEGF induces

206 Romanian Journal of Legal Medicine Vol. XXII, No 3(2014) the differentiation and proliferation of angioblasts within the decrease of NaCl concentration. Epitheliocytus endothelial cells. VEGF and receptors play a key role in the maculae densae controls sodium (Na+) concentration in development process of the kidney, through differentiation glomerular filtrate within proximal convoluted tubule. of endothelial cells, capillary formation and tubular Mesangiocytus extraglomerularis has an agranular epithelium proliferation. cytoplasm and phonotypical is similar with mesangiocytus An important role in the maintenance of structure intraglomerularis, but the functional role is still unknown. and function of glomerular capillary ultrafiltation was The complexity of renal parenchyma morphogenesis assumed by a pericapillary interstitial tissue, named, processes by involvement of stem cells populations raise according to Zimmermann (1933) [7] “supportive questions about the existence and localization of stem cells conjunctive tissue of glomerular capillaries” and within adult kidney. Recent studies have identified locations homologated by International of stem cells inside renal parenchyma in adults.Oliver (2004) as mesangium [42]. Mesangial cells (Mesangiocytus) are demonstrated that the main location of stem cells is renal incorporated within mesangial matrix (Matrix mesangialis). papilla, where the tension is low. Herzlinger (1994) They are similar to muscular cells, posses a great variability [38]; Meshina et al. (2003) [39] and Challer et al. (2006) in shape and volume and accomplish various functions: [39] consider that stem cells exist also at the level of cortical contractility, fagocitosis, syntesis of mesangial matrix and tubular system. Park et al. (2010) [41] also identified nests basal membrane, storage and transport of some complex of stem cells within . The presence of these chemical substances and not the least, they participate cells in adult kidney, through their capacity of creating in the scarring process of glomerular lesions (Beregi, renal parenchyma cells, raises the question about their 1978)[27]. Mesangial matrix contains fibers, contribution in , in tissue regeneration and renal mucopolysaccharides and participates in the balance of failure therapy. blood flow inside glomerular capillaries (Georgescu L, 1978)[28]. Mesangial cells contract under the influence of CONCLUSIONS , control the blood flow inside capillaries and influence glomerular filtration (Mente, 1996)[29]. Sakai 1. Anatomic, rigorous assessment of renal and Kriz (1987) [30]] named “mesangial angle” the direct parenchyma, which has a heterogeneous structure, relation between mesangial matrix and glomerular basal requires the systematic examination of embryo derivates membrane. It has a mechanic role, applying traction onto from nephrogenic mesoderm mesenchyme (Mesoderma the glomerular basal membrane, counterbalancing the intermedium) existing within renal cortical and medullar. hydraulic force which determines ultrafiltration (Kriz et 2. Genesis and evolution of renal structures depend al., 1990) [31]. Proliferation of mesangial cells was noticed on reciprocal interactions and interductions between two in (Iidaka et al., 1968) [32], embryonic conjunctive tissues emerged from nephrogenic in compensatory hypertrophy (Olivetti et al., 1980) [33], mesoderm: mesonephros mesenchyme (Mesonephros) in immunologic (Couser, 1990) [34]. by “ureteric bud” (Diverticulum metanephricum) Similarly, was noticed the growth of mesangial matrix and metanephros mesenchyme (Metanephros) by in different types of glomerulosclerosis and proliferative metanephrogenic bud (Massa metanephrogenica, sin : membranous glomerulonephritis (Heptinstall, 1983 [35]; Metanephrogenic blastema). Spargo et al., 1980 [36]). 3. Metanephrogenic bud assures the synchronic Structural and functional anatomy of renal genesis of two renal structures groups: one nephrovascular parenchyma was added a new subsystem, named (Glomerulus) through vasculogenesis processes and other Goormaghtigh juxtaglomerular apparatus (Goormaghtigh’s nephrotubular, secretory (Tubulus secretorius) through juxtaglomerular apparatus) and homologated as Complexus transdifferentiation processes of metanephrogen bud juxtaglomerularis. It was identified at the level of glomerular mesenchyme into tubular epithelium. hilum, between afferent and efferent arteriolas and 4. The junction between nephrovascular and glomerulus. Three structures have been included within secretory nephrotubular structures determines the shaping this complex: macula densa, tunica media arteriolarum of two anatomic-functional compartments: one for filtration glomerularum and insula perivascularis mesangii (Table (capillary-podocytes barrier) and other for - 1).Juxtaglomerular complex inside renal cortex represents secretion (vascular-epithelial barrier) the major structure of rennin- system and the 5. Disturbances in genesis and evolution program most important place for hydroelectrolythic balance and of renal structures lead to the occurrence of congenital preservation. Three populations of cells have been identified malformations. within juxtaglomerular complex: Epitheliocytus maculae 6. Pathological processes, inflammatory and/ densae, Myocytus juxtaglomerularis and Mesangiocytus or degenerative may determine side effects at the level of extraglomerularis. Miocytus juxtaglomerularis, located anatomic-functional embryologic compartments, through inside middle tunica of afferent arteriola, secrets which a nosological classification of renal pathology can be rennin, as a response to Beta-1 adrenergic stimulation, achieved. to the decrease of renal pressure and to

207 Dragoi G.S. et al The significance of reciprocal induction relations between the derivates of nephrogenic mesoderm

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