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Ultrastructure of Glomerulus and Juxtaglomerular Apparatus

Yashpal S. Kanwar, Manjeeri A. Venkatachalam

10.1002/cphy.cp080101

Source: Supplement 25: Handbook of Physiology, Renal Physiology

Originally published: 1992

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Glomerulus
1.1 Cells
1.2 Extracellular Matrices
1.3 Biosynthetic Features
1.4 Ultrafiltration Unit
1.5 Permeability Characteristics
1.6 Glomerular Polyanions: Structure and Function
1.7 Role of Sialoglycoproteins
1.8 null
2 Juxtaglomerular Apparatus
2.1 Polar Cushion
2.2 Afferent and Efferent Arterioles
2.3 Macula Densa
2.4 Peripolar Cells
2.5 Structural—Functional Relationships
Figure 1. Figure 1.

A: low‐magnification electron micrograph of network of glomerular capillaries (Cap). Capillaries are made of 3 cell types: visceral epithelial (Ep), endothelial (En), and mesangial (Me); and 2 extraglomerular matrices: glomerular basement membrane (GBM) and mesangial matrix (MM). Parietal epithelium (Pe) lines Bowman's capsule (BC) from inside. RBC, red blood cell, × 3,000. B: high magnification electron micrograph of ultrafiltration unit, consisting of epithelial foot processes (fp) of epithelial cell (Ep) with intervening slit diaphragms (Sd), GBM, and fenestrated (fn) endothelium (En). GBM consists of lamina densa (LD), lamina rara interna (LRI), and lamina rara externa (LRE). × 60,000.

From Kanwar 114
Figure 2. Figure 2.

A: electron micrograph of portion of glomerulus showing anatomical relationships of epithelium (Ep), endothelium (En), and mesangial (Me) cells with glomerular basement membrane (GBM) and mesangial matrix (MM). GBM consists of lamina densa (LD), lamina rara interna (LRI), and lamina rara externa (LRE). GBM is covered by the visceral epithelial foot processes (fp) from outside, whereas it is lined inside by fenestrated (fn) endothelium. Mesangial cell (Me) is embedded in MM and surrounded by intercapillary channels (Ic). US, urinary space, × 6,000 B: Schematic drawing of A.

Courtesy of J. Anastasi
Figure 3. Figure 3.

Scanning electron micrograph of glomerular capillary viewed from outside (A) and inside (B). Podocytes (Po) send interdigitating foot processes (fp) that cover capillaries from outside. Endothelium (En, arrows) lines capillary from inside, and its cytoplasm is attenuated and has numerous fenestrae (arrowheads). RBC, red blood cell. A, × 5,000; B, × 10,000.

From Kanwar 114
Figure 4. Figure 4.

High‐magnification electron micrographs of portion of glomerular capillary. A: cell surface sialoglycoproteins (SGP) covering epithelial foot processes (fp) stained with colloidal iron. B: anionic sites of glomerular basement membrane (GBM) contain groups of cationic ferritin particles (arrowheads) in lamina rara externa and interna GBM. Cap, capillary lumen; US, Urinary space, × 80,000.

From Kanwar 114
Figure 5. Figure 5.

A: light micrograph of acellular glomerulus prepared by detergent treatment. Basement membranes (GBM), capillary loops (Cap), and mesangial matrices (MM) are evident. B: light‐microscopic autoradiogram of acellular glomeruli from kidneys perfused with [35S] sulfate to label proteoglycans of extracellular matrices. Autoradiographic grain density is much greater in the MM than in GBM, which indicate a higher turnover rate of sulfated molecules in MM. US, urinary space, × 800.

From Kanwar et al. 127
Figure 6. Figure 6.

Light immunohistomicrographs of glomeruli from kidney sections stained with antibodies to type IV collagen (A), core protein of heparan sulfate proteoglycan of glomerular basement membrane (B), fibronectin (C), laminin (D), entactin (E), and actomyosin (F).

Courtesy of Drs. Chung, Courtoy, Makino and Scheinman
Figure 7. Figure 7.

Electron‐microscopic autoradiograms of glomerular capillary loops (Cap) from kidneys, untreated (A) and treated with he‐paritinase (B), after perfusion with [35S] sulfate to label de novo synthesized proteoglycans. A: almost all grains are associated with basement membranes (GBM) or mesangial matrix (MM). B: after treatment with heparitinase all grains from GBM are removed; however, intracellular grains predominantly located in terminal saccules of Golgi apparatus of epithelial cell (Ep) are unaffected. US, urinary space; fp, foot processes; En, endothelium, × 15,000.

From Kanwar et al. 130
Figure 8. Figure 8.

A: electron micrograph of the slit diaphragm (Sd) as viewed en face, revealing highly organized zipperlike substructure. Central filament and cross‐bridges, indicated by bars, are well resolved, × 150,000 B: electron micrograph of loop of glomerular capillary (Cap) from kidney of animal that received cationic ferritin intravenously and was sacrificed 15 min later. Large number of particles are visible underneath Sd. GBM, glomerular basement membrane; fp, foot processes; US, urinary space; fn, fenestrae; En, endothelium, × 60,000.

A from Karnovsky 199.] [B from Kanwar, 114
Figure 9. Figure 9.

Effects of molecular size, charge, and shape on entry of macromolecules into hypothetical capillary membrane and filtrate. Filtering element of capillary is represented as gel comprised of intertwining elongated chains with fixed negatively charged moieties. A (top): entry of uncharged molecules into gel framework, and thus into filtrate, is governed by steric interactions only. Available water volume within gel for soluble molecules decreases with increasing molecular size. Middle: for molecules of equal size, entry of molecules into gels is determined by electrophysical interactions. Thus with decreasing net negative charge, filtration is enhanced. Bottom: Loosely coiled, elongated molecules without tertiary structure (e.g., dextrans), pictured on left, undergo deformation during filtration; transit of deformed molecules through gel is facilitated. This phenomenon is termed reptation. In contrast, globular proteins, pictured on right, are not susceptible to unravelling their polypeptide chains because of more rigid tertiary structure. Thus, for same hydrodynamic radii measured for them in free solution, transit of globular proteins through gel matrix is retarded relative to that of linear‐chain polymers. B: fractional clearances of cationic diethylaminoethyl (DEAE) dextran, neutral dextran, and anionic dextran sulfate, plotted as function of effective molecular radius in normal rats. Relative clearances of dextrans are as follows: DEAE dextran > neutral dextran » dextran sulfate.

A from Venkatachalam and Rennke 279; B from Bohrer et al. 21
Figure 10. Figure 10.

Diagrams summarizing permeability of glomerular capillary wall to peroxidatic (A) and dextran (B) tracers, determined by electron microscopy. Peroxidatic tracers, including cytochrome C (CYTO‐c), horseradish peroxidase (HRP), myeloperoxidase (MPO), and catalase, are restricted to a variable degree in the various strata of capillary; while dextrans either freely permeate across or are totally restricted by glomerular basement membrane (BM) at level of endothelium (En). Ep, epithelium; LRI, lamina rara interna; LRE, lamina rara externa; LD, lamina densa.

Data from Caulfield and Farquhar 42 and Karnovsky and Ainsworth 133
Figure 11. Figure 11.

Portions of glomerular capillary (Cap) loops from control kidneys that were perfused with native ferritin (A and B) and cationic ferritin (C and D). Native ferritin does not enter the normal glomerular basement membrane (GBM), whereas cationic ferritin binds to anionic sites in the lamina rara interna (LRI) and lamina rara externa (LRE) (A and C). After treatment with heparitinase (B and D), native ferritin penetrates into deeper layers of GBM (B), and cationic ferritin does not bind to anionic sites but forms a gradient across GBM (D) similar to that of native ferritin (B). Some ferritin particles can be seen beneath slits (arrow in D). fp, foot processes; US, urinary space; En, endothelial fenestrae; LD, lamina densa. × 80,000

From Kanwar 114
Figure 12. Figure 12.

Light microscopic autoradiograms of capillary loops (Cap) from control (A) and heparitinase‐treated (B) kidneys that were subsequently perfused with 125I‐labeled bovine serum albumin. After enzymatic treatment, capillary wall offers no restriction to passage of 125I‐labeled bovine serum albumin into urinary space (US). Magnification × 1,500.

From Rosenzweig and Kanwar 222
Figure 13. Figure 13.

Model illustrating clogging of glomerular basement membrane (GBM) by various macromolecules after neutralization of anionic charge of GBM by perfusion of kidneys with Krebs‐Ringer bicarbonate (KRB) buffers of high molarity. When kidneys are perfused with native ferritin (NF), bovine serum albumin (BSA), and insulin in vehicle of 0.15 M KRB (physiologic molarity), negatively charged GBM restricts passage of macromolecules on basis of their size and charge such that native ferritin does not reach urinary space (US) at all and bovine serum albumin does so only to limited extent. Insulin, which has an Einstein‐Stokes radius < 18, passes freely across GBM from capillary lumina (CL) to urinary space. In addition negatively charged groups of GBM (sulfates and carboxyls) protect GBM from being clogged because charged groups remain hydrated and prevent hydrophobic interactions between GBM and macromolecules in solution being filtered (in this case native ferritin, bovine serum albumin, and insulin), resulting in normal GFR. In contrast, neutralization of anionic charge of GBM by perfusion with high molarity (1.5 M) KRB (in which molarity is adjusted by addition of NaCl) results in abolition of charge barrier of GBM by deactivation of negative charges (by formation of sodium salts), leading to increase in entry and accumulation of macromolecules in GBM (clogging) and reduction in permeability of GBM to freely filterable molecules such as insulin and even water. Of GBM negative charges, only sulfates are depicted in diagram.

From Kanwar and Rosen‐zweig 126
Figure 14. Figure 14.

A: low‐power electron micrograph of glomerulus from kidney perfused with Krebs‐Ringer bicarbonate buffer (KRB) alone for 10 min. Note lacy pattern created by slender interdigitating foot processes. Epithelial cell (Ep) bodies remain separate from one another as well as from underlying foot processes (fp). × 5,000 B: low‐power electron micrograph of glomerulus from kidney perfused with KRB containing 50 μg ml protamine sulfate for 10 min. Note extensive effacement of epithelial foot process (fp) architecture. Large masses of epithelial cytoplasm are apposed to glomerular basement membrane. Epithelial cell bodies make intimate contact with one another and with underlying flattened foot processes, × 4,000 C: electron micrograph of capillary (Cap) of glomerulus incubated for 10 min with cationic ferritin. Note swelling of epithelial foot processes (fp) and obliteration of intervening space. Numerous patches of aggregated actin filaments (arrowheads) art visible in the cytoplasm of foot processes. CF, cationic ferritin; Ep epithelium; En, endothelium; Me, mesangium; US, urinary space, × 60,000

B From Seiler et al. 238; C from Kanwar 114
Figure 15. Figure 15.

A: glomerular capillary from control kidney perfused sequentially with buffer, aldehyde fixative, and colloidal iron (CI), pH 1.6, to demonstrate the sialic acid‐rich surface coats on epithelial foot processes (fp) and endothelial (En) membranes. Staining is noticeably heavier on tops and sides of foot processes (above slit membranes) where they face urinary spaces (US) than at base of foot processes where they face glomerular basement membrane (GBM). Note that CI particles also bind to lamina rara interna (LRI) and lamina rare externa (LRE). B: portion of glomerulus [including part of mesangial region (Me)] from kidney perfused with neuraminidase before perfusion with aldehyde fixative and CI. Several areas (*) where there is detachment of foot processes (fp) from the GBM are evident, as is general detachment of endothelium. There is complete absence of CI binding to epithelial cell surface, indicating complete removal of sialic acid. Split diagraphs are broken and disrupted in places (arrow) and GBM appears thin and pale‐staining (especially to left). CI deposits on luminal side of GBM are assumed to represent residues of unfiltered CI. LD, lamina deansa; Cap, capillary lumen, × 80,000.

From, Kanwar and Farquhar 118
Figure 16. Figure 16.

A: a portion of glomerular capillary from kidney perfused with native ferritin in Krebs‐Ringer bicarbonate‐bovine serum albumin (KRB‐BSA). A few particles enter glomerular basement membrane (GBM) and most are retained in inner layers of GBM. × 100,000 B: a region of glomerular capillary from neuraminidase‐treated kidney that was subsequently perfused with native ferritin in KRB‐BSA. Epithelium is detached from GBM, creating subepithelial pocket (between asterisks). Native ferritin penetrates GBM, accumulates in subepithelial pocket, and from there reaches urinary space (US) by means of gaps in slit diaphragms between detached foot processes (fp). Cap, capillary lumen, × 100,000.

From Kanwar and Rosenzweig 125
Figure 17. Figure 17.

Light micrograph (a), its schematic drawing (b), and scanning micrograph of methyl methacrylate cast (c) showing relationship of various components of juxtaglomerular apparatus (JGA) with glomerular capillaries (Cap). A, afferent arteriole; E, efferent arteriole; EGMR, extraglomerular mesangial region; En, endothelium; Gc, granular cell; MD, macula densa; US, urinary space.

Courtesy of J. Anastasi and H. Rennke
Figure 18. Figure 18.

A: electron micrograph of portion of juxtaglomerular apparatus showing arteriolar endothelial (En) lining, granular cell (Gc) and distal tubular epithelial cell (DTEc) of macula densa (MD). Gc contains numerous membrane‐bound granules (gr). × 8,000. B: high‐magnification electron micrograph of Gc showing various forms of granules (gr), most of which are round, some rhomboid, and others elongated with crystalline appearance. Some resemble lysosomes (Ly). Nu, nucleus; Go, Golgi complex, × 16,000.
Figure 19. Figure 19.

Light micrograph (immunoperoxidase) of glomeruli from serial sections of kidney stained with antirenin (A) and angiotensin II (B) antibodies. Co‐localization of renin and angiotensin II (indicated by brown reaction product, arrows) is observed in arteriolar walls. G, glomerulus; T, tubules, × 800.

Courtesy of T. Inagami
Figure 20. Figure 20.

Electron micrographs of granular cell with immunolabeled Golgi complexes (Go), secondary vacuoles (Sv), and immature protogranules (Ig). Labeling is seen in the form of electron‐dense colloidal gold particles. In B, immature granule contains crystalline material (arrow), probably representing immunoreactivity toward renin. A, × 35,000; B, × 55,000; C, × 30,000.

From La Casse and Cantin 152
Figure 21. Figure 21.

Electron micrographs of part of granular cell with immunolabeled Golgi complexes (Go), immature protogranules (Ig), and mature granules (Mg). Immunogold particles indicate presence of renin in various types of granules, × 35,000.

Courtesy J. La Casse and M. Cantin


Figure 1.

A: low‐magnification electron micrograph of network of glomerular capillaries (Cap). Capillaries are made of 3 cell types: visceral epithelial (Ep), endothelial (En), and mesangial (Me); and 2 extraglomerular matrices: glomerular basement membrane (GBM) and mesangial matrix (MM). Parietal epithelium (Pe) lines Bowman's capsule (BC) from inside. RBC, red blood cell, × 3,000. B: high magnification electron micrograph of ultrafiltration unit, consisting of epithelial foot processes (fp) of epithelial cell (Ep) with intervening slit diaphragms (Sd), GBM, and fenestrated (fn) endothelium (En). GBM consists of lamina densa (LD), lamina rara interna (LRI), and lamina rara externa (LRE). × 60,000.

From Kanwar 114


Figure 2.

A: electron micrograph of portion of glomerulus showing anatomical relationships of epithelium (Ep), endothelium (En), and mesangial (Me) cells with glomerular basement membrane (GBM) and mesangial matrix (MM). GBM consists of lamina densa (LD), lamina rara interna (LRI), and lamina rara externa (LRE). GBM is covered by the visceral epithelial foot processes (fp) from outside, whereas it is lined inside by fenestrated (fn) endothelium. Mesangial cell (Me) is embedded in MM and surrounded by intercapillary channels (Ic). US, urinary space, × 6,000 B: Schematic drawing of A.

Courtesy of J. Anastasi


Figure 3.

Scanning electron micrograph of glomerular capillary viewed from outside (A) and inside (B). Podocytes (Po) send interdigitating foot processes (fp) that cover capillaries from outside. Endothelium (En, arrows) lines capillary from inside, and its cytoplasm is attenuated and has numerous fenestrae (arrowheads). RBC, red blood cell. A, × 5,000; B, × 10,000.

From Kanwar 114


Figure 4.

High‐magnification electron micrographs of portion of glomerular capillary. A: cell surface sialoglycoproteins (SGP) covering epithelial foot processes (fp) stained with colloidal iron. B: anionic sites of glomerular basement membrane (GBM) contain groups of cationic ferritin particles (arrowheads) in lamina rara externa and interna GBM. Cap, capillary lumen; US, Urinary space, × 80,000.

From Kanwar 114


Figure 5.

A: light micrograph of acellular glomerulus prepared by detergent treatment. Basement membranes (GBM), capillary loops (Cap), and mesangial matrices (MM) are evident. B: light‐microscopic autoradiogram of acellular glomeruli from kidneys perfused with [35S] sulfate to label proteoglycans of extracellular matrices. Autoradiographic grain density is much greater in the MM than in GBM, which indicate a higher turnover rate of sulfated molecules in MM. US, urinary space, × 800.

From Kanwar et al. 127


Figure 6.

Light immunohistomicrographs of glomeruli from kidney sections stained with antibodies to type IV collagen (A), core protein of heparan sulfate proteoglycan of glomerular basement membrane (B), fibronectin (C), laminin (D), entactin (E), and actomyosin (F).

Courtesy of Drs. Chung, Courtoy, Makino and Scheinman


Figure 7.

Electron‐microscopic autoradiograms of glomerular capillary loops (Cap) from kidneys, untreated (A) and treated with he‐paritinase (B), after perfusion with [35S] sulfate to label de novo synthesized proteoglycans. A: almost all grains are associated with basement membranes (GBM) or mesangial matrix (MM). B: after treatment with heparitinase all grains from GBM are removed; however, intracellular grains predominantly located in terminal saccules of Golgi apparatus of epithelial cell (Ep) are unaffected. US, urinary space; fp, foot processes; En, endothelium, × 15,000.

From Kanwar et al. 130


Figure 8.

A: electron micrograph of the slit diaphragm (Sd) as viewed en face, revealing highly organized zipperlike substructure. Central filament and cross‐bridges, indicated by bars, are well resolved, × 150,000 B: electron micrograph of loop of glomerular capillary (Cap) from kidney of animal that received cationic ferritin intravenously and was sacrificed 15 min later. Large number of particles are visible underneath Sd. GBM, glomerular basement membrane; fp, foot processes; US, urinary space; fn, fenestrae; En, endothelium, × 60,000.

A from Karnovsky 199.] [B from Kanwar, 114


Figure 9.

Effects of molecular size, charge, and shape on entry of macromolecules into hypothetical capillary membrane and filtrate. Filtering element of capillary is represented as gel comprised of intertwining elongated chains with fixed negatively charged moieties. A (top): entry of uncharged molecules into gel framework, and thus into filtrate, is governed by steric interactions only. Available water volume within gel for soluble molecules decreases with increasing molecular size. Middle: for molecules of equal size, entry of molecules into gels is determined by electrophysical interactions. Thus with decreasing net negative charge, filtration is enhanced. Bottom: Loosely coiled, elongated molecules without tertiary structure (e.g., dextrans), pictured on left, undergo deformation during filtration; transit of deformed molecules through gel is facilitated. This phenomenon is termed reptation. In contrast, globular proteins, pictured on right, are not susceptible to unravelling their polypeptide chains because of more rigid tertiary structure. Thus, for same hydrodynamic radii measured for them in free solution, transit of globular proteins through gel matrix is retarded relative to that of linear‐chain polymers. B: fractional clearances of cationic diethylaminoethyl (DEAE) dextran, neutral dextran, and anionic dextran sulfate, plotted as function of effective molecular radius in normal rats. Relative clearances of dextrans are as follows: DEAE dextran > neutral dextran » dextran sulfate.

A from Venkatachalam and Rennke 279; B from Bohrer et al. 21


Figure 10.

Diagrams summarizing permeability of glomerular capillary wall to peroxidatic (A) and dextran (B) tracers, determined by electron microscopy. Peroxidatic tracers, including cytochrome C (CYTO‐c), horseradish peroxidase (HRP), myeloperoxidase (MPO), and catalase, are restricted to a variable degree in the various strata of capillary; while dextrans either freely permeate across or are totally restricted by glomerular basement membrane (BM) at level of endothelium (En). Ep, epithelium; LRI, lamina rara interna; LRE, lamina rara externa; LD, lamina densa.

Data from Caulfield and Farquhar 42 and Karnovsky and Ainsworth 133


Figure 11.

Portions of glomerular capillary (Cap) loops from control kidneys that were perfused with native ferritin (A and B) and cationic ferritin (C and D). Native ferritin does not enter the normal glomerular basement membrane (GBM), whereas cationic ferritin binds to anionic sites in the lamina rara interna (LRI) and lamina rara externa (LRE) (A and C). After treatment with heparitinase (B and D), native ferritin penetrates into deeper layers of GBM (B), and cationic ferritin does not bind to anionic sites but forms a gradient across GBM (D) similar to that of native ferritin (B). Some ferritin particles can be seen beneath slits (arrow in D). fp, foot processes; US, urinary space; En, endothelial fenestrae; LD, lamina densa. × 80,000

From Kanwar 114


Figure 12.

Light microscopic autoradiograms of capillary loops (Cap) from control (A) and heparitinase‐treated (B) kidneys that were subsequently perfused with 125I‐labeled bovine serum albumin. After enzymatic treatment, capillary wall offers no restriction to passage of 125I‐labeled bovine serum albumin into urinary space (US). Magnification × 1,500.

From Rosenzweig and Kanwar 222


Figure 13.

Model illustrating clogging of glomerular basement membrane (GBM) by various macromolecules after neutralization of anionic charge of GBM by perfusion of kidneys with Krebs‐Ringer bicarbonate (KRB) buffers of high molarity. When kidneys are perfused with native ferritin (NF), bovine serum albumin (BSA), and insulin in vehicle of 0.15 M KRB (physiologic molarity), negatively charged GBM restricts passage of macromolecules on basis of their size and charge such that native ferritin does not reach urinary space (US) at all and bovine serum albumin does so only to limited extent. Insulin, which has an Einstein‐Stokes radius < 18, passes freely across GBM from capillary lumina (CL) to urinary space. In addition negatively charged groups of GBM (sulfates and carboxyls) protect GBM from being clogged because charged groups remain hydrated and prevent hydrophobic interactions between GBM and macromolecules in solution being filtered (in this case native ferritin, bovine serum albumin, and insulin), resulting in normal GFR. In contrast, neutralization of anionic charge of GBM by perfusion with high molarity (1.5 M) KRB (in which molarity is adjusted by addition of NaCl) results in abolition of charge barrier of GBM by deactivation of negative charges (by formation of sodium salts), leading to increase in entry and accumulation of macromolecules in GBM (clogging) and reduction in permeability of GBM to freely filterable molecules such as insulin and even water. Of GBM negative charges, only sulfates are depicted in diagram.

From Kanwar and Rosen‐zweig 126


Figure 14.

A: low‐power electron micrograph of glomerulus from kidney perfused with Krebs‐Ringer bicarbonate buffer (KRB) alone for 10 min. Note lacy pattern created by slender interdigitating foot processes. Epithelial cell (Ep) bodies remain separate from one another as well as from underlying foot processes (fp). × 5,000 B: low‐power electron micrograph of glomerulus from kidney perfused with KRB containing 50 μg ml protamine sulfate for 10 min. Note extensive effacement of epithelial foot process (fp) architecture. Large masses of epithelial cytoplasm are apposed to glomerular basement membrane. Epithelial cell bodies make intimate contact with one another and with underlying flattened foot processes, × 4,000 C: electron micrograph of capillary (Cap) of glomerulus incubated for 10 min with cationic ferritin. Note swelling of epithelial foot processes (fp) and obliteration of intervening space. Numerous patches of aggregated actin filaments (arrowheads) art visible in the cytoplasm of foot processes. CF, cationic ferritin; Ep epithelium; En, endothelium; Me, mesangium; US, urinary space, × 60,000

B From Seiler et al. 238; C from Kanwar 114


Figure 15.

A: glomerular capillary from control kidney perfused sequentially with buffer, aldehyde fixative, and colloidal iron (CI), pH 1.6, to demonstrate the sialic acid‐rich surface coats on epithelial foot processes (fp) and endothelial (En) membranes. Staining is noticeably heavier on tops and sides of foot processes (above slit membranes) where they face urinary spaces (US) than at base of foot processes where they face glomerular basement membrane (GBM). Note that CI particles also bind to lamina rara interna (LRI) and lamina rare externa (LRE). B: portion of glomerulus [including part of mesangial region (Me)] from kidney perfused with neuraminidase before perfusion with aldehyde fixative and CI. Several areas (*) where there is detachment of foot processes (fp) from the GBM are evident, as is general detachment of endothelium. There is complete absence of CI binding to epithelial cell surface, indicating complete removal of sialic acid. Split diagraphs are broken and disrupted in places (arrow) and GBM appears thin and pale‐staining (especially to left). CI deposits on luminal side of GBM are assumed to represent residues of unfiltered CI. LD, lamina deansa; Cap, capillary lumen, × 80,000.

From, Kanwar and Farquhar 118


Figure 16.

A: a portion of glomerular capillary from kidney perfused with native ferritin in Krebs‐Ringer bicarbonate‐bovine serum albumin (KRB‐BSA). A few particles enter glomerular basement membrane (GBM) and most are retained in inner layers of GBM. × 100,000 B: a region of glomerular capillary from neuraminidase‐treated kidney that was subsequently perfused with native ferritin in KRB‐BSA. Epithelium is detached from GBM, creating subepithelial pocket (between asterisks). Native ferritin penetrates GBM, accumulates in subepithelial pocket, and from there reaches urinary space (US) by means of gaps in slit diaphragms between detached foot processes (fp). Cap, capillary lumen, × 100,000.

From Kanwar and Rosenzweig 125


Figure 17.

Light micrograph (a), its schematic drawing (b), and scanning micrograph of methyl methacrylate cast (c) showing relationship of various components of juxtaglomerular apparatus (JGA) with glomerular capillaries (Cap). A, afferent arteriole; E, efferent arteriole; EGMR, extraglomerular mesangial region; En, endothelium; Gc, granular cell; MD, macula densa; US, urinary space.

Courtesy of J. Anastasi and H. Rennke


Figure 18.

A: electron micrograph of portion of juxtaglomerular apparatus showing arteriolar endothelial (En) lining, granular cell (Gc) and distal tubular epithelial cell (DTEc) of macula densa (MD). Gc contains numerous membrane‐bound granules (gr). × 8,000. B: high‐magnification electron micrograph of Gc showing various forms of granules (gr), most of which are round, some rhomboid, and others elongated with crystalline appearance. Some resemble lysosomes (Ly). Nu, nucleus; Go, Golgi complex, × 16,000.



Figure 19.

Light micrograph (immunoperoxidase) of glomeruli from serial sections of kidney stained with antirenin (A) and angiotensin II (B) antibodies. Co‐localization of renin and angiotensin II (indicated by brown reaction product, arrows) is observed in arteriolar walls. G, glomerulus; T, tubules, × 800.

Courtesy of T. Inagami


Figure 20.

Electron micrographs of granular cell with immunolabeled Golgi complexes (Go), secondary vacuoles (Sv), and immature protogranules (Ig). Labeling is seen in the form of electron‐dense colloidal gold particles. In B, immature granule contains crystalline material (arrow), probably representing immunoreactivity toward renin. A, × 35,000; B, × 55,000; C, × 30,000.

From La Casse and Cantin 152


Figure 21.

Electron micrographs of part of granular cell with immunolabeled Golgi complexes (Go), immature protogranules (Ig), and mature granules (Mg). Immunogold particles indicate presence of renin in various types of granules, × 35,000.

Courtesy J. La Casse and M. Cantin
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Article Title: Ultrastructure of Glomerulus and Juxtaglomerular Apparatus
 

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Yashpal S. Kanwar, Manjeeri A. Venkatachalam. Ultrastructure of Glomerulus and Juxtaglomerular Apparatus. Compr Physiol 2011, Supplement 25: Handbook of Physiology, Renal Physiology: 3-40. First published in print 1992. doi: 10.1002/cphy.cp080101