Renal Anatomy And Physiology

Renal Anatomy Renal Anatomy Vimar A. Luz, MD, FPCP, DPSN M.D.

Rosella N. Blancas,

Gross Features: • • • • • • • • •

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paired retroperitoneal organ Upper pole: T12; Lower pole: L3 Weight: adult man: 125 -170 g adult woman: 115 - 155 g Length: 11 to 12 cm Width: 5.0 to 7.5 cm Thickness: 2.5 to 3.0 cm Hilus: renal pelvis, the renal artery and vein, the lymphatics, and a nerve. Blood supply: single renal artery Anterior branch: 3 segmental or lobar arteries supply the upper, middle, and lower thirds of the anterior surface of the kidney Posterior branch: > ½ of the posterior surface; small apical segmental branch

Gross Features Relation to other layers: • The renal fascia relates to the other layers in the following manner (moving from innermost to outermost): renal cortex renal capsule perinephric fat (or "perirenal fat") renal fascia paranephric fat (or "pararenal fat") peritoneum (anteriorly) transversalis fascia (posteriorly)

Cut surface of a bisected kidney: •

pale outer region (the cortex) • darker inner region (the medulla) 8 to 18 striated conical masses (renal pyramids) Base: corticomedullary boundary Apex: renal pelvis to form a papilla : 10 - 25 small openings that represent the distal ends of the collecting ducts (of Bellini) → area cribrosa

Renal cortex: - 1 cm in thickness - renal columns of Bertin - "medullary rays of Ferrein“ - formed by the collecting ducts and the straight segments of the proximal and distal tubules. • Renal pelvis: expanded portion of the upper urinary tract • Major calyces: 2 or 3 outpouchings, extend outward from the upper dilated end of the renal pelvis Minor calyces: extend toward the papillae of the pyramids and drain the urine formed by each pyramidal unit. Ureters: lower portion of the renal pelvis at the ureteropelvic junction, descend a distance ∼ 28 - 34 cm to open into the fundus of the urinary bladder.

THE NEPHRON • •

functional unit of the kidney 0.4 × 10 6 to 1.2 × 10 6 Essenttal components: renal or malpighian corpuscle (glomerulus and Bowman's capsule) proximal tubule the thin limbs distal tubule connecting segment or connecting tubule •Two main populations of nephrons: (1) possessing a short loop of Henle (7x more) (2) long loop of Henle

THE NEPHRON

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Length of the loop of Henle is generally related to the position of its parent glomerulus in the cortex. Superficial and midcortical locations : short loops of Henle Juxtamedullary region: long loops of Henle

Division of the kidney (cortical & medullary )and the further subdivision of the medulla (inner and outer zones) : relating renal structure to the ability of an animal to form a maximally concentrated urine Countercurrent hypothesis for urine : the maximal urine concentration that can be achieved is directly related to the length of the multiplier system.

Renal Corpuscle (Glomerulus) • •

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capillary network lined by a thin layer of endothelial cells central region of mesangial cells with surrounding mesangial matrix material the visceral epithelial cells (Podocytes) and the associated basement membrane average diameter: 200 µm The diameters of glomeruli from juxtamedullary nephrons: are 20% greater than superficial glomeruli

Renal Corpuscle (Glomerulus) • Responsible for the production of an ultrafiltrate of plasma • Filtration barrier 4.fenestrated endothelium 5.peripheral GBM 6.slit pores between the foot processes of the visceral epithelial cells • Mean area of filtration surface per glomerulus: 0.136 mm2 in the human kidney

Mesangial cells

Parietal Epithelial cell

Endothelial cell

Visceral Epithelial cell

Endothelial cell • • •

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glomerular capillaries are lined by a thin fenestrated endothelium human kidney range fr 70 - 100 nm Thin diaphragms: extend across the fenestrae w/c when present, are not believed to represent a significant barrier to the passage of macromolecules. surface is negatively charged because of the presence of a polyanionic surface glycoprotein, podocalyxin (principal sialoprotein of glomerular epithelial cells)

Endothelial cell • • •

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synthesize both nitric oxide (EDRF) and endothelin-1 (vasoconstrictor) Express vascular endothelial growth factor (VEGF) receptors VEGF: regulator of microvascular permeability that is produced by the glomerular VEC (Podocytes) - In vitro studies demonstrated that VEGF increases endothelial cell permeability and induces the formation of endothelial fenestrations. - endothelial cell survival and repair in glomerular diseases and an important regulator of endothelial cell function and permeability. form the initial barrier to the passage of blood constituents from the capillary lumen to Bowman's space. contribute to the charge-selective properties of the glomerular capillary wall through their negative surface charge.

Visceral Epithelial Cells (podocytes) • •

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largest cells in the glomerulus long cytoplasmic processes (trabeculae) that extend from the main cell body and divide into individual foot processes (pedicels), that come into direct contact with the GBM. Distance between adjacent foot processes near the BM: 25 to 60 nm. filtration slit membrane (slit diaphragm) - 60 nm. fr the BM. - role in establishing the permselec tive properties of the filtration barrier is still a matter of dispute.

Filtration slit / slit pore

Visceral Epithelial Cells (podocytes) Nephrin protein - a key component of filtration barrier • membrane components on the surface of the visceral epithelial cells (slit diaphragm) CD2-associated protein (CD2AP) – slit diaphragm; connect nephrin to cytoskeleton Functions: Endocytosis (lysosomes ) uptake of proteins and other components from the ultrafiltrate Synthesis and maintenance of the GBM, type IV collagen, and glycosaminoglycan , PgE2 and thromboxanes.

Mesangial Cells • •

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Mesangium : cells + matrix Irregular in shape, with a dense nucleus and elongated cytoplasmic processes that can extend around the capillary lumen and insinuate themselves between the BM and the overlying endothelium. provides structural support for the glomerular capillary loops contractile properties regulation of glomerular filtration exhibit phagocytic properties (clearance or disposal of macromolecules from the mesangium) generation and metabolism of the extracellular mesangial matrix and participate in various forms of glomerular injury

Glomerular Basement Membrane •

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central dense layer (lamina densa) two thinner, more electron-lucent layers, the lamina rara externa and the lamina rara interna layered configuration results from the fusion of endothelial and epithelial BM during development. mean width: 315 nm - 329 nm biochemical composition: glycoproteins (type IV collagen, laminin, fibronectin, entactin/ nidogen, various heparan sulfate proteoglycan (perlecan and agrin)

Glomerular Basement Membrane • • •

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possesses fixed, negatively charged sites that influence the filtration of macromolecules anionic sites : glycosaminoglycans rich in heparan sulfate Glomerular capillary wall: sieve or filter that allows the passage of small molecules but almost completely restricts the passage of molecules the size of albumin or larger. size-selective and charge-selective properties Fenestrated endothelium GBM epithelial slit diaphragm Fenestrated endothelium (negative surface charge) excludes formed elements of the blood and probably plays a role in determining the access of proteins to the GBM - - - plays a role in establishing the ultrafiltration characteristics of the glomerular capillary wall. principal structure responsible for the charge-selective permeability properties of the glomerulus

Parietal Epithelial cells •

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parietal epithelium: forms the outer wall of Bowman's capsule - continuous with the visceral epithelium at the vascular pole. - squamous in character, but at the urinary pole there is an abrupt transition to the taller cuboid cells of the proximal tubule thickness of the BM of Bowman's capsule :1200 to 1500 nm. In RPGN the parietal epithelial cells proliferate to contribute to the formation of crescents.

Peripolar Cells: • •

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component of the JG apparatus located at the origin of the glomerular tuft in Bowman's space and is interposed between the visceral and parietal epithelial cells In most animals studied so far, they have been localized predominantly in glomeruli in the outer cortex are ideally situated to release factors into Bowman's space that might affect subsequent tubule transport events.

Juxtaglomerular Apparatus •

Juxtaglomerular Apparatus • •

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located at the vascular pole of the glomerulus Vascular component: composed of the terminal portion of the afferent arteriole, the initial portion of the efferent arteriole, and the extraglomerular mesangial region. Tubule component : macula densa, (that portion of the thick ascending limb that is in contact with the vascular component) Represents a major structural component of the reninangiotensin system. Role: regulate glomerular arteriolar resistance and GF and to control the synthesis and secretion of renin.

Juxtaglomerular Granular Cells Within the vascular component: 2. Juxtaglomerular granular cells (epithelioid / myoepithelial cells) 3. Agranular extraglomerular mesangial cells (lacis cells or pseudomeissnerian cells of Goormaghtigh) • Located primarily in the walls of the afferent and efferent arterioles, but they are also present in the extraglomerular mesangial region. • are characterized by the presence of numerous membrane-bound granules that represent renin or its precursor. • Immunohistochemical studies: presence of both renin and angiotensin II in the JG granular cells, with activities being highest in the afferent arteriole.

Extraglomerular Mesangium (Lacis / Cells of Goormaghtigh) • •

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Located between the afferent and efferent arterioles in close contact with the macula densa In contact with the arterioles and the macula densa, and gap junctions are commonly observed between the various cells of the vascular portion of the JG apparatus Serve as a functional link between the macula densa and the glomerular arterioles and mesangium.

EM

Macula Densa •

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a specialized region of the thick ascending limb adjacent to the hilus of the glomerulus. lacks the lateral cell processes and interdigitations that are charac teristic of the thick ascending limb. sense changes in the luminal concentrations of Na and Cl via absorption of Na and Cl across the luminal membrane by the Na+ -K+ -2Cl- cotransporter.

Proximal Tubule • • • •

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begins abruptly at the urinary pole of the glomerulus Length:14 mm (human); Outside diameter: 40 µm Reabsorbs the bulk of filtered water and solutes Prominent brush border (↑ luminal cell surface area) and extensive interdigita tion by basolateral cell processes that extends to the leaky jxn providing a greatly increased passage for the passive ion transport Generally divided into 3 segments: S1, S2, S3

Proximal Tubule It consists of: Pars convoluta (initial convoluted portion) - direct continuation of the parietal epithelium of Bowman's capsule Pars recta (straight portion) - located in the medullary ray; contains a well-developed endocytic-lysosomal apparatus that is involved in the reabsorption and degradation of macromolecules from the ultrafiltrate.

Loop of Henle: Consists of: 2. Straight portion of the proximal tubule 3. Thin ascending limb - impermeable to water 5. Thin descending limb - highly permeable to water (aquaporin-1) 7. Thick ascending limb (diluting segment) - water impermeable (carried away into the cortex to the systemic circ.) but reabsorbs considerable amounts of salt that is trapped in the medulla(Na-K-2Cl cotransporter) - Tam-Horsefall pretein Before transition to the DCT. Thick AL contains the macula densa.

Distal Covoluted Tubule •

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Exhibits the most extensive basolateral interdigitation of cells and greatest density of mitochondria. Na-Cl cotransporter – speific Na transporter (Thiazide diuretics)

COLLECTING DUCT SYSTEM Includes: • Connecting tubule • Cortical collecting ducts • Medullary CD Outer MCD Inner MCD Connecting tubule (CNT) : - Joining of 2 nephrons - 2 types of cell: 1. CNT cell 2. Intercalated cell Both share sensitivity to ADH; CNT cell lacks sensitivity to mineralocorticoids

Collecting Ducts: Lined by 2 types of cells: 2. Principal cells (CD) Contain luminal shuttle system for aquaporin -2 under the control of vasopressin (permeability from zero to permeable) • Luminal Amloride-sensitive Na channel – involved in the responsiveness of the cortical collecting ducts to aldosterone. • Inner medulary collecting ducts – expresses urea transporter UTB1 w/c in an ADH – dependent fashion accounts for the recycling of urea (urine concentrating mechanism)

Collecting Ducts: 2. Intercalated cells (IC) 2 types: a. Type A cells – express H-ATPase at their luminal memb.; secretes proton b. Type B – basolateral membrane; secrete HCO3 ions and reabsorb protons. • Final regulators of fluid and electrolye balance • Impt roles in handling NA,Cl, K and acid-base. • Urine concentrating capability

INTERSTITIUM •

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Comparatively sparse: 5-7%: cortex (↑ w/ age); 3-4%: outer stripe; 10%: inner stripe 30%: inner medulla Fibroblast: central cells; forms the scaffold frame renal cortex: ecto 5 nucleotidas enzyme (5’-NT) – synthesizes epoetin renal medulla: Lipid-laden IC; produce large amount of glycosaminoglycans and Vasoactive lipids (Pg E2) Dendritic cells- MHC class II antigen Extracellular matrix, fibrils and interstitial fluid

Thank You !

Thank Renal Anatomy You ! M.D.

Rosella N. Blancas,