Urinary system Aleš Hampl • 1. Regulating blood volume and pressure • 2. Regulating plasma concentrations of sodium, potassium, chloride and other ions • 3. Stabilising blood pH • 4. Conserving nutrients • 5. Detoxifying poisons (with the liver) Functions of urinary system Components of urinary system Kidneys Paired bean-shaped retropertioneal 11 x 4-5 x 2-3 cm Stroma •Capsule dense fibroelastic connective tissue myofibroblast layer •Interstitial stroma loose fibroelastic connective tissue Parenchyma •Nephrons •Collecting ducts •Vascular components Urethers Urinary bladder Urethra Urinary tract Dense fibroelastic connective tissue Myofibroblast layer Kidneys capsule Overall organization of kidney LateralMedial Hilum – portal for renal vessels, nerves and urether Renal sinus – cavity deep to hilum occupied by renal pelvis and vessels Renal pelvis – expansion of ureter, extension to major and minor calyces Renal parenchyma – medulla + cortex Renal collumn Extension of cortex into medulla •Cortex •Medulla Renal pyramid 10 to 18 per kidney Lobe Cortical arch Lobullar structure of the kidney Renal collumn Extension of cortex into medulla •Cortex •Medulla Renal pyramid 10 to 18 per kidney Pyramid Renal papila Base Area cribrosa Minor calyx DB-ducts of Bellini Kidney medulla Kidney cortex Renal corpuscles Cortical labyrinth (convoluted tubules) Cortical rays (continuation of collecting ducts from renal pyramids) Uriniferous tubule = The functional unit of the kidney Ducts of Bellini Area cribrosa Minor calyx Cortex Medulla Nephron Collectingtubuli+ducts 1 to 1.4 milllions of nephrons in one kidney Nephrons X Collecting tubuli + ducts Different embryological origin renal corpuscle Nephron Cortical nephrons 85% of nephrons Juxtamedullary nephrons 15% of nephrons About 40 mm long Nephron Nephron – Renal corpuscle 1 Glomerulus – tuft of capillaries Bowman`s capsule - invaginated dilatation of proximal tubule Masson stain 200-250m side of the corpuscle where the PCT exits. side of the corpuscle where the afferent arterioles and efferent arterioles enter and exit, respectively Vascular pole Urinary pole Nephron – Renal corpuscle 2 Bowman’s space Nephron – Glomerulus 1 Endothelial cell Endothelial cell Endothelial cell pores Foot processes of podocyte Foot processes of podocyte Mesangial cell Capillary Capillary Capillary Basal lamina Endothelial cell + Basal lamina + Podocytes + Mesangial cells Mesangial cells - Contractile - receptors for angiotensin II - Give structural support to the glomerulus, synthesize ECM - Endocytose and dispose of normal and pathologic molecules trapped by the glomerular basement membrane - Produce chemical mediators such as cytokines and prostaglandins Lamina Rara – contain fibronectin (bind them to cells) – physical barrier Lamina Densa – meshwork of Type IV collagen and laminin in a matrix contg (-) charged heparan sulfate that restricts passage of cationic molecules – charge barrier Nephron – Glomerulus 2 Nephron – Glomerulus 3 Capillary lumen Endothelial cell Fenestra Podocyte Foot processes of podocyte Basal lamina Fenestra: 70 – 90 nm Lamina rara externa Lamina densa Lamina rara interna Filtration slit with 6 nm filtration diaphragm Fenestrum (about 80 nm) 20-40 nm Nephron – Glomerulus – Podocyte 1 Nephron – Glomerulus – Podocyte 2 Fenestrum Podocytes Filtration slit with 6 nm filtration diaphragm Primary processes X Secondary processes Nephron – Glomerulus – Podocyte 3 SEM of Podocyte covering glomerular capillaries „Octopus-like cell“ Nephron – Glomerulus – Podocyte Nephron – Tubular section 1 Proximal convoluted tubulus Henle`s loop •Thick descending limb •Thin limb •Thick ascending limb Distal convoluted tubulus Proximal convoluted tubulus + Thick descending limb of HL = 14 mm in length PCT PCT PCT PCT PCT 60 m PCT Nephron – Tubular section 2 Reabsorption ¾ of sodium, Cl, K, H2O, amino acids, proteins Proximal convoluted tubuli Thin descending limb of HL + Thin ascending limb of HL = 9-10 mm in length HL HL 15-20 m HL Nephron – Tubular section 3 Reabsorption H2O Thick ascending limb of HL + Distal convoluted tubulus 9-10 mm in length + 4-5 mm in length DCT DCT 30-40 m Nephron – Tubular section 4 Reabsorption Na, K, Cl Impermeable for water Proximal and distal convoluted tubuli P P PD D Cortex Proximal X Distal convoluted tubuli (7:1) Nephron – Tubular section – Juxtaglomerular apparatus 1 Macula densa Monitors osmotic concentration in the fluid in the nephron and secretes local hormones that alter JG cell secretion. Juxtaglomerular cells Monitor blood pressure in the afferent arteriole and secrete renin. Renin converts angiotensinogen in blood plasma to angiotensin I which is converted to angiotensin II in the lungs. Angiotensin II causes arteriole constriction throughout the body, raising blood pressure. Extraglomerular mesangial cells (Lacis cells) Macula densa Modified DCT in proximity of vascular pole of renal corpuscle Nephron – Tubular section – Juxtaglomerular apparatus 2 Juxtaglomerular cells Collecting tubuli Cortical + Medullary + Papillary = 20 mm in length • Conserve body fluids • Reacts to ADH (antidiuretic hormone) of the posterior pituitary gland • ADH increases the permeability of the collecting tubules and distal tubules to water so more is reabsorbed • This decreases the total volume of urine • Alcohol inhibits the release of ADH, so less water is reabsorbed producing copious amounts of dilute urine (can cause dehydration) 200 -300 m Collecting Collecting Proximal Long section of Collecting and proximal tubuli Blood circulation Renal vein Abdominal aorta Renal artery Vena cava inferior Subdivision into 5 arteries (segmented blood supply) Renal artery Arcuate artery Arcuate vein Cortical radiate artery Cortical radiate vein Blood circulation Blood circulation – Afferent + Efferent arterioles Blood circulation – Peritubular capilaries Peritubular capilaries arise from efferent arterioles of cortical nephrons •low-pressure, porous capillaries •absorb solutes •their endothelia manufacture erythropoietin (?) Vasa recta •arose from efferent arterioles of juxtamedullary nephron •thin walled looping vessels •10-25 mm long •part of the kidney’s urine-concentrating mechanism Blood circulation – Vasa recta VR VR VR Excretory passages •Calyces (minor + major) •Pelvis •Ureters •Urinary bladder •Urethra General organizational pattern (calyces, pelvis, urethers, bladder) •Mucosa Luminal sheet epithelium (transitional) Basal lamina Lamina propria/submucosa (connective tissue) •Lamina muscularis (smooth muscle) •Lamina adventitia or serosa Renal calyces + pelvis • Minimal lamina propria (submucosa) • Thin tunica muscularis • Tunica adventitia – blends with adipose tissue in the renal sinus Ureters (25-30 cm long) •Carry urine from renal pelvis to the urinary bladder •Same wall layers as pelvis •Ureter wall thickens and the muscle cells change from a helical to longitudinal array near the bladder •Urine moves by active peristaltic motion Epithelium (3-5 layers) Circular m. (outer) Longitudinal m. (inner) Propria (fibroelastic) Adventitia Lumen 3 – 5 mm Urinary bladder Thick muscularis - near the opening into the urethra  they form an involuntary internal sphincter. Epithelium Lamina propria Lamina adventitia Smooth muscle (detrusor muscle) Epithelium Basal membrane Lamina propria longitudinal+circular+longitudinal thin + thick + thin Urinary bladder Emptied Distended with urine External urinary sphincter Female urethra (4-5 cm in length) Transitional epithelium •Transitional + stratified squamous nonkeratinizing ep. •Folded mucosa (due to fibroelastic propria) •Two-layered muscularis •Glands of Littre Spongy - penile Near the tip of penis – fossa navicularis Stratified squamous epithelium (nonkeratinizing) A) Tunica albuginea C) Corpus spongiosum (erectile) Arrows) Glands of Littre Prostatic urethra - transitional ep., opennings of prostate gland Membranous urethra – stratified collumnar ep., through the urogenital diaphragm Spongy (penile) urethra – stratified collumnar + squamous ep. Male urethra (15-20 cm in length) Dialysis x Kidney transplant x Kidney regeneration ? cloaca Urogenital system – Overall picture Urogenital system – Reminder Urogenital system – Intermediate mesoderm Urogenital system – Early forms of kidneys - Pronephros Recapitulation of three stages of evolution of kidneys in a cranial to caudal sequence: • pronephros • mesonephros • metanephros Nephrotomes Nephric duct Nephrotomes • at about day 22 in cervical part of nephrogenic cord • 7 to 10 groups of epithelial cells • connect to pronephric duct • non-functional • disappear by day 28 pronephros pronephric duct The lumen of each nephrotome opens into the primary nephric duct as well as into the body cavity. Glomeruli form as small vessels extend from the dorsal aortae. Mouse D9 – equivalent to human D27 Urogenital system – Early forms of kidneys - Pronephros Urogenital system – Early forms of kidneys - Mesonephros Mesonephros • caudal continuation of nephrogenic cord • thoracolumbar region • unsegmented intermediate mesoderm • mesonephric ducts (paired) – Wolffian ducts • mesonephric tubuli – open individually into m. duct • 36 to 40 m. tubuli in total (on one side) • some filtration – mesonephric unit • mesonephros is most prominent when metanephros start to shape – active since week 6 til week 10 • then they diasappear fast • mesonephric ducts persist in males Urogenital system – Mesonephros - Another view Urogenital system – Definitive kidneys - Metanephros Ureteric bud = metanefric diverticulum + Metanephrogenic blastema (mesenchyme) Develop since week 5 Branching and Elongation 14 to 15 x Urogenital system – Definitive kidneys - Metanephros Repeated branching of ureteric bud produces: • ureter • pelvis • calyces (major + minor) • collecting tubuli (1 to 3 millions) Uriniferous tubule = The functional unit of the kidney Ducts of Bellini Area cribrosa Minor calyx Cortex Medulla Nephron Collectingtubule 1 to 1.4 milllions of nephrons in one kidney Nephrons X Collecting tubules Different embryological origin renal corpuscle Urogenital system – Metanephros - Nephrons • arched ampulous endings of ureteric ducts (collecting tubuli) – capping by condensed mesenchyme • part of the cap cells differentiate into nephrogenic vesicle • vesicles elongate • vesicles open to the collecting tubulus on one end • distal from the ducts, the cells of elongating vesicles polarize and form lumen and basal lamina • precursors of endothelia grow into this area - glomerulus • endothelia connect to branches of dorsal aorta – gromerular circulation • production of urine since week 10 Urogenital system – Metanephros - Nephrons Urogenital system – Metanephros - Nephrons • about 15 successive generations of nephrons in peripheral zone of kidney • outermost nephrons are less mature Cortical nephrons Juxtamedulary nephrons Urogenital system – Definitive kidneys - Metanephros 5 weeks 6 weeks 8 weeks • ventral outpocketing of the hindgut • sac-like structure (respiration) • in umbilical cord • proximal part – URACHUS – continuos with bladder • URACHUS – transforme to Median umbilical ligament 4.5 weeks Urinary system - Bladder Cloaca = terminal part of the hindgut + allantois Urogenital simus Urogenital septum Primitive rectum Urogenital membrane Anal membrane PerineumCloaca Urinary system – Bladder + Ureters + Urethra • alantois expands - urinary bladder • initially bladder is continuos with alanotois – then obliteration – urachus – median umbilical ligament • caudal portions of mesonepric ducts become absorbed by the bladder wall – separation – ureters + ejaculatory ducts Posterior view Urachus Primitive urethra Ureter Ureter Trigone Ejaculatory duct Urinary system – Congenital anomalies 1. Agenesis 2. Duplication 3. Anomalies of shape 4. Abnormal of position 5. Congenital polycystic kidney Horseshoe kidney Thank you for your attention ! Questions and comments at: ahampl@med.muni.cz