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STRUCTURE OF THE KIDNEY DR SANTOSH SUBEDI RESIDENT DM NEPHROLOGY 2020
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TOPICS FOR DISCUSSION GROSS ANATOMY CUT SECTION MICROSCOPY/HISTOLOGY REFERENCES
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KIDNEYS Paired Bean-shaped, in retroperitoneal space, either side of spine. Each weighs about 125 to 170 gram Upper pole : T12 and Lower pole : L3 Right kidney is slightly lower than left Size : 11-12 cm x 5-7.5 cm x 2.5-3 cm Hilum : slit, renal artery and vein, renal pelvis, nerves, lymphatics Capsule : Thin, tough, fibrous tissue surrounding each kidneys.
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Blood supply Kidneys receive around 20 % Cardiac Output. A pair of renal artery and their tributaries Branch of abdominal aorta at level L1/L2 Supplies the kidney as well as carries blood for filtration After entering through hilum it divides in to anterior and posterior division Anterior to posterior : VEIN, ARTERY, PELVIS.
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SEGMENTS
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INTERLOBULAR INTERLOBULAR
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Cut surface OUTER PALE : CORTEX INNER DARK : MEDULLA 8 to 18 : Pyramids : Base : CMJ : Apex : PAPILLA EACH PAPILAE HAS 10 -25 OPENING OF THE COLLECTING DUCT : DUCTS OF BELLINI
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Renal lobus : pyramid with associated cortex.
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Renal lobe : Pyramid with associated with cortex Renal lobule : Collection of nephrons draining to common collecting duct Functional unit
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Pelvocalyceal system Collecting system Lined by transitional epithelium 2-3 major calyces Many minor calyces : extend to papillae : drain urine. Ureters : pelvis to fundus of bladder : 28 to 35 cm
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Kidney : histology 1. Nephrons 3. Collecting ducts 4. Microvasculature 2. Supporting cells Interstitium
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NEPHRONS The functional unit of the kidney Approximately 1 million nephrons in each kidney The number of nephron is already established during prenatal period After birth, new nephrons cannot be developed, and a lost nephron cannot be replaced
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Types of Nephron
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Parts of nephron Each nephron consists of Renal corpuscle /Glomerulus Long tubule segmented into Proximal tubule Loop of Henle Distal tubule
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Renal corpuscle/glomerulus Glomerular Capillaries lined by endothelium GBM Podocytes and foot process. Mesangium : supporting cells Bowman’s capsule : a pouch to capture and direct the filtrate to PCT
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Endothelium Highly fenestrated round to oval pores : 50 to 100 nm Luminal membrane is negatively charged due to presence of several polyanionic glycoproteins, including podocalyxin.
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Glomerular Basement Membrane Skeleton of the glomerular tuft. The outer aspect is covered with podocytes. The inner aspect filled with the capillary endothelium and mesangium The major components of the GBM include Type IV collagen, Laminin 11, Heparan sulfate proteoglycans (-VE charge) Type IV collagen is the antigenic target in Goodpasture’s disease Mutations in the genes of type IV collagen : Alport’s syndrome
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Glomerular Filtration Barrier Urine formation begins at the glomerular filtration barrier The ultrafiltrate has to pass three layers: the fenestrated endothelium the intervening glomerular basement membrane. Podocyte with slit diaphragm
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Podocytes Have large cell body and extensive array of foot processes Foot processes interdigitate with slit diaphragm The luminal membrane : Thick surface coat rich in sialoglycoproteins ( podocalyxin/podoendin) Responsible for the high negative surface charge The abluminal membrane : Two transmembrane proteins : α3β1 integrin, β-α- dystroglycans Connect the cytoskeleton to GBM.
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PODOCIN & NEPHRIN Constituent protein of slit pore diaphragm Inactivating mutation leads to severe proteiuria
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Mesangium Mesangial cells and mesangial matrix Mesangial cells: Irregular, many processes extending to GBM Dense assembly of microfilament : actin, myosin and alfa actinin Mesangial Matrix : Fills irregular spaces between mesangial cells & perimesangial GBM Contains collagen, microfibrillar proteins, glycopprotein and proteoglycans
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THE TUBULE Single-layer flat/cuboidal epithelium anchored to a basement membrane Parts
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The proximal tubule The PCT has prominent brush border, and extensive interdigitated basolateral infoldings. Approximately 14 mm long, diameter 40 uM Large prominent mitochondria Subdivided into three segments S1 & S2 : PARS CONVOLUTA S3 : PARS RECTA
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Loop Of Henle Comprises of Terminal Straight Portion PCT : water permeable Thin Ascending Limb : water impermeable : osmotic medullary gradient Thick Ascending Limb : Diluting segment Na K 2Cl cotransporter : acted upon by loop diuretics Tamm Horsefell Protein : cast and crystal formation Macula densa
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Distal tubule Extensive basolateral interdigitation Abundant mitochondria Luminal micro villi. Luminal NaCl cotransporter : THIAZIDES
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COLLECTING DUCT SYSTEM Comprises Connecting tubule Cortical collecting duct Medullary collecting duct : outer/inner Connecting tubule : CNT cells & Intercalated cells Collecting tubule : CD (Principal) cells & Intercalated cells CNT cells are only ADH responsive CD cells are both ADH & mineralocorticoid responsive
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CD/Principal cells Polygonal Luminal Aquaporin 2 : ADH sensitive. Luminal Amiloride sensitive Na Channel : Aldosterone responsive. Urea Transporter UTB1 : ADH responsive urea recycle. Intercalated cells Both in CNT, CDT Type A : Luminal H+ATPase : secrete proton Type B : Basolateral H+ATPase : secrete HCO3, : reabsorb proton
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JUXTAGLOMERULAR APPARATUS Macula Densa Extraglomerular mesangium Terminal affrent arteriole with granular JG cells : Renin Beginning of efferent arteriole MACULA DENSA (tightly packed cells with large nucleus) Specialized cells in Thick ascending limb where the limb attaches to EGM of parent glomerulus Regulates the tone of afferent arteriole and thereby glomerular blood flow and GFR: TUBULOGLOMERULAR FEEDBACK
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Juxtaglomerular cells Located in the granules of terminal afferent arteriole Secrete and store RENIN
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RENAL INTERSTITIUM Comparatively sparse, 5 -7% of cortex, 3-30% of medulla Comprises of resident fibroblast and migrating cells from the immune system the dendritic cells The space between the cells is filled with extracellular matrix (proteoglycans, glycoproteins), fibrils, and interstitial fluid. Maintain scaffold frame for glomerulus, tubules & blood vessels.
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References Brenner and Rectors THE KIDNEY 9th ed Comprehensive Clinical Nephrology 4th ed Greenberg primer on Kidney Disease 5th ed.
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Thank you
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DEVELOPMENT OF KIDNEYS
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TOPICS INTRODUCTION STAGES OF KIDNEY DEVELOPMENT NEPHROGENESIS BRANCHING MORPHOGENESIS NEPHRON ENDOWMENT REFERENCES
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Kidney development : NEPHROGENESIS Begins at 28th day after fertilization Completes at 8 months of gestation.
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Vertebrate kidneys arises from the intermediate mesoderm of the urogenital ridge which is present along posterior wall of abdomen in developing fetus. Developmentally three pair of kidneys arise sequentially in mammalian embryo namely the pronephros, mesonephros and the metanephros .
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Mesoderm : paraxial/intermediate/splanchnic
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Urogenital ridge
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The pronephros and mesonephros are transient structures which are reabsorbed during early fetal life. The metanephros develops into the adult kidneys.
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The pronephros The nephric duct originates in the thoracic region, along with pronephric tubule at around 22 days The nephric duct with its tubule at this stage is known as PRONEPHROS It also known as the precursor to the wolffian duct/Mesonephros It is functional in larval stage of fish and amphibians.
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The mesonephros The mesonephros develops caudal to the pronephric tubules in the midsection of the urogenital ridge. The Ureteric bud (UB) is first visible as an outgrowth at the distal end of the wolffian duct at 4th week of gestation . The mesonephros becomes the functional excretory apparatus in lower vertebrates (adult fish and amphibians).
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In humans the mesonephros The mesonephros in male gives rise reproductive organs : Rete Testes, Efferent Ducts, Epididymis, Vas Deferens, Seminal Vesicle and Prostate. In female the mesonephros degenerates .
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The metanephros Metanephros appears at around 32 days It develops from the Ureteric bud epithelium (UB) and clusture of cells known as metanephric mesenchyme (MM) Metanephros : future the adult kidney
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RECIPROCAL INDUCTION BETWEEN URETETIC BUD AND METANEPHRIC MESENCHYME NEPHROGENESIS glomerulus & tubules BRANCHING MORPHOGENESIS CD, Pelvocalyceal system
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Reciprocate inductive interaction MM cause the UB to branch into a T-tubule which then to undergo iterative branching, giving rise to the urinary collecting system and all of the collecting ducts UB sends reciprocal signals to the MM, to condense along the surface of the bud. Following condensation, a subset of MM cells aggregates known as pretubular aggregates, undergo mesenchymal-to-epithelial conversion to become the renal vesicle and nephron
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Ingrowth of the epithelial ureteric bud (b) into the metanephric mesenchyme (m).
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Cells adjacent to invading UB are induced to undergo mesenchymal to epithelial transformation. Initially the mesenchyme aggregate to form 4-5 thick cell layers called the CAP CONDENSATE around the advancing UB. Near the interface of ampulla and its adjacent ureteric branch a clusture of cells separate to form an oval mass called the PRETUBULAR AGGREGATE.
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An internal cavity forms within the pretubular aggregate to form the RENAL VESICLE Multiptential precursors in renal vesicle gives rise to all epithelial cell types of nephron. Nephron segmentation into glomerular and tubular domain is initiated by the sequential formation of two clefts in the renal vesicle. Creation of lower cleft (Vascular cleft) leads formation of comma shaped body.
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Generation of upper cleft in in the comma shaped body lead to formation of S shaped body with 3 segments : First segment – Glomerulus Second segment – Proximal tubule Third segment - Loop of Henle and DCT.
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Formation of glomerulus begins as the vascular cleft broadens and as lower limb of S shaped body forms cup shaped unit. Epithelial cells lining inner wall of cup comprise visceral or podocyte layer. Cells lining the outer wall of the cup forms the parietal cell layer that lines the Bowmen’s Capsule. Glomerular capillary tuft is formed by recruitment and proliferation of angioblast and mesangial precursor cells.
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The visceral epithelial cells and the endothelium make up the Glomerular Basement Membrane. Podocyte layer revert to mesenchymal type phenotype, flatten and spread out to cover increased surface area of growing capillary bed. Mesangial cells populate the core of the tuft and provides structural support .
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Branching morphogenesis The collecting system and all collecting ducts are the product of branching morphogenesis from the Ureteric Bud. Considerable remodeling occurs in the ureteric bud in the formation of collecting duct and the process is not fully understood The branching is highly patterned earlier symmetric and asymmetric in the later stages. Leading to formation of papilla and calyx. Human kidney has 8 to 10 papillae, each draining into a minor calyx, with several minor calyces draining into a smaller number of major calyces.
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The number of ureteric bud branches is the major determinant of final nephron number as the UB tip induces discrete subset of metanephric mesenchyme to undergo nephrogenesis. Repetitive branching events result in formation of 15 branch generations. Nephrogenesis is completed by 32nd to 34th weeks of gestation.
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Nephron Endowment It is the total number of functional nephron present at birth The number of nephron reaches maximum at 34th weeks of gestation At birth, total average number of nephron is 1 million in each kidney. There is no formation of new nephrons after birth rather the number only decreases through natural ageing, disease or surgical ablation.
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Females have fewer nephrons than males Infants born before 32nd weeks of gestation have relative nephron deficits. Individuals at lower end of nephron endowment have increased incidence of hypertension, cardiovascular disease, diabetes and ESKD
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BRENNER, 1988, congenital (programmed) reduction in number of nephrons predisposes to hypertension and renal injury
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Surrogates of adverse intrauterine environment and low renal number
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REFERENCES PRIMER ON KIDNEY DISEASE 7TH ED BRENNER AND RECTORS THE KIDNEY 9TH ED OXFORD TEXTBOOK OF CLINICAL NEPHROLOGY 4TH ED
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Renal Malformation Congenital anomalies of kidneys and urinary tract (CAKUT) malformation of