The Development and Structure of the Kidney

1. URINARY TRACT – I The kidney Maria M. Picken MD, PhD mpicken@lumc.edu Renes = latin kidneys nephros = greek kidney

2. Outline: I – the kidney development gross structure vasculature glomerulus II – the structure and function of the tubules renal pelvis ureter urinary bladder urethra

3. Objectives: General objectives: - to identify the kidney’s structures, function and location - to analyze the relationship between microscopic structure and function Specific objectives: 1. To identify elements of the gross and microscopic structure of the kidney and analyze the relationship between them 2. To list the special features of renal vasculature and correlate these with function 3. To describe and analyze the structure and function of the glomerulus as a whole 4. To describe and analyze the structure and function of the glomerular filtration barrier 5. To identify elements of the nephron and the collecting system 7. To contrast and compare the structure and function of different segments of the nephron 8. To evaluate the relationship between the vasculature and the nephron 9. To identify the elements of the juxtaglomerular apparatusand define their relationship to each other 10. To identify the general structural features of the ureters, the urinary bladder and the urethra 11. To contrast and compare the male versus the female urethra

4. Retroperitoneum, • Thoracic vertebra12-Lumbar vertebra3 • 115-170 g (M>F) • 11-12 x 5-7.5 x 2.5-3 cm • Kidneys – paired, bean shaped • Ureters – paired • urinary bladder • Urethra, male versus female • Renes = latin kidneys • Nephros = greek kidney (Nephrology) • Function: • Filter blood & reabsorb nutrients • Control water, ion, and salt balance of the body • Maintain acid-base balance of the blood • Excrete metabolic wastes (urea and uric acid), toxins, drug components • Secrete hormones (renin, erythropoietin) • Produce calcitriol (active form of vitamin D – absorption of dietary calcium into the blood)

5. Kidney development through a series of successive phases: • the pronephros (most immature) • mesonephros • metanephros (most developed) which persists as the definitive adult kidney • The final stage of kidney development, metanephros, arises caudal to the mesonephros at 5 weeks of development. • As the kidney develops in the elongating fetus, it 'ascends' from its original location (adjacent to the developing bladder) • to its mature location in the retroperitoneum, just caudal to the diaphragm. • As the kidney moves cephalad (towards the head) relative to the bladder, it takes new arterial supply from the aorta and • new venous drainage into the vena cava. • Kidney development is complex and developmental abnormalities are relatively common. They constitute an • important consideration in pediatric nephrology. • http://www.meddean.luc.edu/lumen/MedEd/urology/nlrendev.htm

6. Kidney structure: bean shaped • - capsule • - cortex (outer) • - medulla (inner) • - hilum (pelvis, ureter, renal artery, vein) • Cortex, renal columns (septa) of Bertin • (cortical tissue on either side of the medullary pyramids) • Medulla divided into several (8-18) – conical pyramids • Papillae at apex of medullary pyramid • Papillae lead into minor calyces • Minor Calyces lead into 2-3 major calyces • Major Calyces lead to the expanded upper end of the ureter called the renal pelvis (latin: pelvis=basin) Glossary: capsule - a structure enclosing an organ, usually composed of dense connective tissue cortex - the outer portion of an organ, distinguished from its inner, medullary portion hilus or hilum - a depression or pit at that part of an organ where the vessels and nerves enter medulla - the inner portion of an organ, usually in the center. See also: http://www.bu.edu/histology/m/glossary.htm

7. on either side of medullary pyramid Posterior division of renal artery Interlobular arteries • Kidney blood supply: • 0.5% of total body weight, 25% of the cardiac output • renal artery, anterior & posterior divisions, segmental arteries (do not anastomose, “end arteries”) • interlobar arteries on either side of medullary pyramid • - arcuate artery (Latin = curved) between cortex and medulla, parallel to kidney surface), interlobular arteries

8. juxtamedullary glomerulus Posterior segment • interlobular arteries → afferent arteriole → glomerulus → efferent arterioles • efferent arterioles in the cortex form peritubular capillary plexus • - efferent arterioles of juxtamedullary nephrons (juxta [Latin]close to) • go into medulla and loop back “vasa recta” (straight vessels [Latin]) Afferent, from afferre [Latin] = to bring toward Efferent, from efferre [Latin] = to bring out • Correlation with pathology: • - cortex: 90% of blood supply • - medulla is relatively a-vascular (10%, low oxygenation) • tubular capillary beds derived from the efferent arterioles • acute tubular necrosis (injury), papillary necrosis

9. vascular pole Bc * tubular pole Glomerulus in paraffin section: Bowman’s capsule (Bc) + glomerular tuft* Afferentarterioles arise from interlobular vessels and supply the glomeruli Efferent arterioles arise from glomerular capillaries

10. Glomerulus Paraffin section • network of capillaries: • - mesangium: cells & matrix • (mes angium = in the middle of vessels) • contractile • phagocytic • proliferation • - endothelium • - basement membrane • -2 layers of epithelium • visceral (aka “podocytes”) – anchored on glomerular basement membrane • parietal – line Bowman’s capsule

12. Urinary space podocyte foot process (pedicel) slit diaphragm pedicellus [Latin] small foot) lamina rara externa glomerular basement membrane lamina densa lamina rara interna blood fenestrated endothelium without diaphragms • Electron microscopy of the glomerular capillary wall (aka glomerular filtration barrier): • - fenestrated endothelium (fenestra [Latin] – window) • - glomerular basement membrane – lamina rara interna & externa, lamina densa • visceral epithelial cells (podocytes) – foot processes, filtration slits with thin diaphragm • Note: other capillaries in the kidney are fenestrated with diaphragms

13. Foot process Schematic drawing of the slit membrane - disruption of the slit diaphragms or destruction of the podocytes can lead to “proteinuria” where large amounts of protein are lost from the blood into urine - effacement of slit diaphragms with “fusion” of the foot processes may be transient and treatable or permanent Examples: minimal change disease, reversible Congenital disorder Finnish-type nephrosis - neonatal proteinuria leading to end-stage kidney failure, caused by a mutation in the nephrin gene.

14. Glomerular filtration barrier – glomerular basement membrane Glomerular basement membrane: combined basal lamina of glomerular endothelium & pedicels High permeability to water & small solutes Impermeability to proteins - size barrier (<70,000 MW and <10 nm in diameter proteins pass easily) - charge dependent restriction Pathology: Proteinuria, loss of charge, slit membrane… Hematuria - loss of integrity, “structural” damage Lamina rara externa & interna = heparan sulphate (-) Lamina densa: collagen type IV, laminin (size)

15. Glomerular filtrate – “primary urine”: 125 ml/min; 180 L/24 hr 124 ml/min reabsorbed… Daily urinary output 1.5 L End of the urinary tract – part I

16. Questions? mpicken@lumc.edu