Microanatomy of Urinary System PDF

Urinary System Dr. Lalit P. Singh Page 1 of 23 URINARY SYSTEM LECTURE LEARNING OBJECTIVES: 4.1.1 Describe the microanatomy and function of the kidney. Describe...

Urinary System Dr. Lalit P. Singh Page 1 of 23 URINARY SYSTEM LECTURE LEARNING OBJECTIVES: 4.1.1 Describe the microanatomy and function of the kidney. Describe the gross anatomical organization of the kidney, including the: cortex, medulla (pyramids), renal sinus, lobes, and lobules. List the parts of a nephron and a uriniferous tubule. Compare and contrast cortical and juxtamedullary nephrons. Describe the blood supply to the medulla and cortex. Describe the microanatomy and functions of a renal corpuscle. Describe the cells found in a renal corpuscle. Describe the fluid compartments found within a renal corpuscle. Describe the structure of glomerular capillaries. Describe the histological organization of the glomerular basement membrane at the TEM level and its function in filtration of the blood. Describe an intraglomerular mesangial cell and its function. Describe the microanatomy and functions of a kidney proximal tubule. Describe the microanatomy and functions of the thin limb in the kidney. Describe the microanatomy and functions of a kidney distal tubule. Compare and contrast the microanatomy of a distal and proximal tubule. Describe the histological organization of the macula densa and its function. Describe the origin, histological organization, and functional role of juxtaglomerular cells. Describe the feedback loop for the regulation of blood pressure that begins with the macula densa. Describe the microanatomy and functions of a collecting duct in the kidney. Describe the function of kidney interstitial cells. Describe the microanatomy and functions of the renal pelvis and ureter. Describe the characteristics of transitional epithelial cells. 4.1.2 Describe the microanatomy and function of the bladder. 4.1.3 Describe the microanatomy and function of the female urethra. Compare and contrast the microanatomy of the female urethra with that of the ureter. Urinary System Dr. Lalit P. Singh Page 2 of 23 Lecture Content Outline I. Kidney A. Cortex B. Medulla C. Renal sinus D. Lobe E. Lobule F. Uriniferous tubule G. Nephron H. Blood supply I. Renal corpuscle J. Proximal tubule K. Thin limb L. Distal tubule M. Collecting tubules (ducts) N. Functional summary O. Interstitial cells P. Excretory passages II. Bladder A. Mucosa B. Muscularis C. Adventitia III. Urethra - female A. Mucosa B. Muscularis Urinary System Dr. Lalitt P. Singh Page 3 of 23 I. Kidney K – a co ompound tub bular gland, which seeparates mettabolic wastees from bloo od and reegulates the composition n of plasma. Major fu unctions incllude filtratio on, secretion,, and ab bsorption. The kidney iss composed of o an outer co ortex and inn ner medulla (Fig. 1). Its surface is co overed by a thin fibrous capsule of fibroblasts f annd myofibroblas m ts. The medu ulla containss cone-shapeed bu undles of tub bules called pyramids (Figs. ( 1, 2). A. A Corteex - peripherral portion which w containns Fig. 1 The Kidney renal corpuscles.. (Pawlina & R Ross, 2015) 1. Renal corp puscle (Malp pighian corpuscle)) = capillary glomeruluss + Bowman n’s capsule. a. Glo omerulus - capillary c loopp derived froom an affferent arterio ole and drainned by an effferent arteriole. Fig. F 2 Kidney Pyramid P Fig. 3 Medu ulary rays (E Erlandsen & Magney) M (Erlandsen & Magney) 2. Cortical tissue is also found f in thee medulla in cortical or umns - (Fig. 1). renal colu 3. Medullary undles of tubbules in the cortex which y rays are bu extend into o the medullla (Fig. 3). Urinary System Dr. Lalit P. Singh Page 4 of 23 B. Medulla - inner portion containing tubules and collecting ducts grouped into pyramids. 1. Pyramids converge to form a papilla (Fig. 2) with a rounded apex, which projects into a minor calyx. 2. Medulla can be subdivided into zones to reflect distribution of tubules. (Identification of zones not required). C. Renal sinus - contains renal pelvis (expanded funnel-shaped portion of ureter) with its major and minor calyces; branches of renal arteries, veins, and nerves, and fatty connective tissue (Fig. 1). D. Lobe - medullary pyramid and the cortical substance associated with it (8 - 18 in humans.) E. Lobule - medullary ray (straight portions of proximal and distal tubules and their collecting ducts) and the cortical tissue associated with it. F. Uriniferous tubule = nephron + connecting or collecting tubule (Fig. 4, see next page). Connecting tubules join nephrons to collecting duct. G. Nephron - the functional unit of the kidney; each kidney has approximately 1 million nephrons. 1. Parts of a nephron a. Renal Corpuscle: Bowman’s capsule - blindly ending tubule indented by Glomerular capillary. b. Proximal thick tubule. i. Proximal convoluted tubule. Urinary System Dr. Lalit P. Singh Page 5 of 23 ii. Proximal straight tubule (aka, descending thick limb). Fig. 4 Uriniferous tubule (Pawlina & Ross, 2015) c. Thin limb - descending and ascending portions. (The loop of Henle includes the entire U-shaped portion of the nephron with its hairpin turn.) d. Distal thick tubule. i. Distal straight tubule (ascending thick limb). ii. Distal convoluted tubule. Urinary System Dr. Lalit P. Singh Page 6 of 23 2. Types of nephrons (Fig. 4) a. Cortical or subcapsular nephrons i. Renal corpuscles are located in outer cortex. ii. Short loops of Henle are confined to the cortex and outer medulla. b. Juxtamedullary nephrons i. Renal corpuscles are located near the corticomedullary junction. ii. Long loops of Henle extend deep into the pyramids and participate in concentration of urine. Fig. 5 Blood Supply Pawlina & Ross, 2015) Urinary System Dr. Lalit P. Singh Page 7 of 23 H. Blood supply (Fig. 5). 1. Renal artery enters kidney at hilus and branches into interlobar arteries, which run between pyramids. 2. Interlobar arteries bifurcate at the corticomedullary junction to form arcuate arteries, which run between the cortex and the base of the pyramids. 3. Arcuate arteries give rise to interlobular arteries, which run radially in cortex between medullary rays. 4. Interlobular arteries give rise to afferent arterioles. 5. Afferent arterioles give rise to glomerular capillaries. 6. Glomerular capillaries coalesce into efferent arterioles draining individual renal corpuscles. The efferent arterioles are of smaller diameter than their afferent counterparts and maintain filtration pressure. a. Efferent arterioles from subcapsular glomeruli form peritubular capillary networks around tubules in the cortex, then drain to arcuate veins. b. Efferent arterioles from juxtamedullary glomeruli usually send vasae rectae arteriae (straight arteries) into the medulla where they make hairpin turns and ascend as venous vasae rectae to join arcuate veins. This pattern of descending and ascending vessels contributes to the counter-current exchange system (e.g., tubular sodium uptake in interstitium, details in physiology lecture). Urinary System Dr. Lalit P. Singh Page 8 of 23 I. Renal corpuscle (Figs. 6, 7) - provides for filtration of plasma from glomerular capillary. It is composed of Bowman’s membrane and the glomerulus, a branched fenestrated capillary. The outer or parietal layer of Bowman’s membrane is reflected inward to partially surround the capillary where it is called the visceral layer of Bowman’s membrane. The afferent arteriole enters the renal corpuscle at the vascular pole (where the efferent arteriole also leaves) and the parietal layer of Bowman’s membrane is continuous with the beginning of a proximal convoluted tubule at the urinary pole. Fig. 7 Parietal layer (Pawlina & Ross, 2015) Fig. 6 Renal Corpuscle (Pawlina & Ross, 2015) 1. Glomerular capillary - fenestrated endothelium with open fenestrae. Urinary System Dr. Lalit P. Singh Page 9 of 23 2. Bowman's capsule - encloses urinary space, which contains provisional urine. a. Parietal or capsular layer (Fig. 7) – simple squamous epithelium. b. Visceral layer – podocytes (Figs. 8, 9) with interdigitating pedicels (foot processes) separated by slit pores spanned by slit membranes. Fig. 9 Podocyte pedicels (Rhodin) Fig. 8 Podocytes (Kessel & Kardon) 3. Filtration barrier. a. Glomerular endothelium with open fenestrae (Fig. 10), but restricts entry of molecules larger Fig. 10 Endothelium and GBM (Erlandsen & Magney) than 70 kD into the glomerular basement membrane (GBM). Some fenestrae with diaphragms are also present. Urinary System Dr. Lalit P. Singh Page 10 of 23 b. Glomerular basement membrane (Fig. 11) – the fused basal laminae of endothelial cells and podocytes. Usually appears trilaminar and contains type IV collagen, heparan sulfate, laminin and fibronectin. The negative charge of heparan sulfate limits movement of negatively charged proteins, less than 70 kD across the GBM although they may enter the GBM. Fig. 11 GBM and Slit membrane (Erlandsen & Magney) c. Slit membrane (Fig. 11) between pedicels is formed by an adhesion protein, nephrin, and its anchoring complex. The slit membrane also contributes to the filtering function of the kidney. d. The relative roles and significance of the GBM and the slit membrane to kidney disease is still under investigation. 4. The polyanionic glycocalyx of the podocytes also limits passage of negatively charged molecules into the filtrate. Urinary System Dr. Lalit P. Singh Page 11 of 23 Clinical correlations Glomerular nephritis - auto-antibodies to GBM produce most severe form (e.g., Goodpasture syndrome). Antigen-antibody complexes can accumulate in the GBM producing acute glomerulonephritis. Congenital nephrotic syndrome - lethal defects in gene producing nephrin. Children have low albumin in blood, high in urine. 5. Mesangial cells (Fig. 12) -- specialized contractile, pericyte-like cells located within stalk of capillary tuft (intraglomerular mesangium) as well as at vascular pole (extraglomerular mesangium). Intraglomerular Fig. 12 Mesangial cell (Ross & Pawlina) mesangial cells participate in maintenance of basement membrane through phagocytosis; provide structural support; regulate blood flow through glomerulus. Also secrete interleukin 1 (IL-1) and platelet derived growth factor (PDGF). Mesangial cells are an unusual example of phagocytic cells not derived from monocytes (they are derived from smooth muscle cells.) Urinary System Dr. Lalitt P. Singh Page 12 of 23 J. Proxiimal tubule - convoluted d and straighht portions (F Fig. 13, see next page). p 1. Functionss - recovery of o about 2/3 of glomerullar filtrate including water, w ions, glucose, am mino acids, sm mall proteinss. ort of Na+ annd passive diiffusion of C There is acctive transpo Cl-. Water follows the ionss by paracelllular and trannscellular routes. Its absorption is i aided by aaquaporin-1 channels in the plasmaa membrane of the proxiimal tubule ccells. Secretion of o creatininee, some dyess and drugs aalso take place here. Fig. 13 Prroximal tubulee (Ross & Pawlina) 2. Morpholo ogy: Simple cuboidal epiithelium (Figs. 14, 15) Fig. 14 Prox ximal tubule – apical brush Fig. 15 EM M of Proximall tubule epitheelium border (Erlandsen ( & Magney) with brush h border (Erlaandsen & Magney) Urinary System Dr. Lalit P. Singh Page 13 of 23 a. Well-developed brush border (apical microvilli), contains peptidases. b. Basal striations and lateral interdigitating folds of the plasma membrane. c. Prominent endocytotic apparatus with pinocytic vesicles, vacuoles, and lysosomes for intracellular degradation. 3. Close proximity to peritubular capillaries. These are typical fenestrated capillaries (with diaphragms). K. Thin limb 1. Simple squamous epithelium with close proximity to vasa rectae (Figs 16, 17). 2. Forms part of loop of Henle along with descending and ascending thick tubules (Fig. Fig. 16 EM of Thick limb to Thin limb 17). transition. (Erlandsen & Magney) 3. Ascending portion of thin limb is essentially impermeable to water, but has a Na+, K+, ATPase pump, which increases the osmotic gradient in the interstitium. This is essential for the Fig. 17 Squamous epithelium of counter-current multiplier Thin limb. (Sobotta) system, which results in a Urinary System Dr. Lalit P. Singh Page 14 of 23 hypertonic urine in the collecting ducts. Inhibition of the pump by diuretics inhibits the uptake of NaCl and increases urinary excretion of NaCl and water. L. Distal tubule (Figs. 18, 19) Fig. 18 Distal tubule with no brush border. - straight and convoluted portions. (Erlandsen & Magney) 1. Simple cuboidal epithelium with few short apical microvilli (no brush border). 2. Extensive system of lateral interdigitations and basal striations with associated mitochondria provides for Fig. 19 EM of distal tubule epithelium. active absorption of Na+ and (Sobotta) bicarbonate with secretion of K+ and H+, the latter contributing to the acidification of urine. 3. Very little endocytotic activity. 4. The straight portion has proximity to vasa rectae; the convoluted portion has close proximity to peritubular capillaries. 5. Macula densa (Figs. 20, 21) - group of tall narrow cells in Fig. 20 Renal corpuscle with macula densa (Ross & Pawlina, 5th ed.) the wall of distal tubule at site of Urinary System Dr. Lalit P. Singh Page 15 of 23 contact with afferent (and efferent) arterioles. Cells respond to a reduction in Na+ content in filtrate and to lowered blood pressure. Cells have a reversed polarity and release their secretion (ATP, adenosine, nitric oxide, prostaglandins) at the basal surface. Forms Fig. 21 Macular densa cells (Erlandsen & Magney) part of the juxtaglomerular apparatus. a. Juxtaglomerular apparatus acts to regulate Na+ absorption and blood pressure and includes: i. Macula densa cells of distal tubule. ii. Juxtaglomerular (JG) cells (Figs. 20, 22) - modified smooth muscle cells (myoepithelioid) in arteriole wall that produce renin, a protease, in Fig. 22 IHC reaction shows in renin staining response to signaling from macula densa cells. Renin catalyzes the hydrolysis of angiotensinogen (a circulating protein in plasma) to angiotensin I which is converted in the lungs to angiotensin II. Angiotensin II is a potent vasoconstrictor and also stimulates the adrenal cortex to produce aldosterone. Aldosterone acts mainly on the collecting tubules and duct to increase Urinary System Dr. Lalitt P. Singh Page 16 of 23 Na+ abssorption, thuus increasingg both bloodd pressurre and volum me. iii. Extrag glomerular m mesangium m - cells are continu uous with inttragolmerulaar mesangium m and derrived similarrly. Their funnction is uncertaain. Clinical correlation ngiotensin co An onverting en nzyme (ACE)) Inhibitors aand ACE recceptor blo ockers (ARB Bs) - ACE in the lung is a potent agennt for increaasing blood preessure becau use it catalyzzes the produ uction of anggiotensin II, a powerful vaasoconstricto or. Some patiients with ch hronic hyperrtension can be treated successfully with w ACE inh hibitors and//or ABRs, wh which interferre with the ren nin-angioten nsin system. M. M Connecting or Collecting tub bules (ductss) (Figs. 23, 24) 1. Arched (in nitial) collectting tubules empty into straight collecting ducts, which h fuse to forrm papillary ducts. 2. Papillary ducts d converrge at apex oof papilla andd open at a minor caly yx. Fig. 23 Collecting g duct Fig. 24 TE EM of collectiing duct epith helium (Erllandsen & Ma agney) ((Erlandsen & Magney) Urinary System Dr. Lalit P. Singh Page 17 of 23 3. Cells lining these ducts are pale staining with few organelles and distinct cell margins (Figs. 23, 24). a. Light (principal) cells, reabsorb Na+, secrete K+, respond mainly to antidiuretic hormone (ADH.) The ADH regulates the insertion of water channels (aquaporin-2) into the cell membranes and increases water uptake. b. Dark (intercalated) cells can reabsorb K+, secrete H+ or HCO3-, thus regulating the acid-base balance. 4. Epithelium of smaller ducts is simple cuboidal but in larger ones, it becomes simple columnar. N. Functional summary (Fig. 25) Urine Volume Regulation - Although all renal corpuscles filter provisional urine and proximal tubules recover Na+, glucose and proteins, it is the juxtamedullary nephrons that are most import in setting up a gradient of Na+ concentration that increases as one goes deeper into the pyramid approaching the papilla Fig. 25 Renal Na+ gradient formation (Fig. 25, ignore arrows). (Pawlina & Ross, 2015) Urinary System Dr. Lalit P. Singh Page 18 of 23 The ascending limbs (thin and thick) are impermeable to water, allowing Na+ concentration to be highest in the deep medulla. The high Na+ concentration can then passively draw water out of the collecting ducts. (ADH regulates the number of aquaporin channels in the collecting duct plasma membrane. The more ADH present, the more highly concentrated the urine becomes and lower its volume). Sodium Concentration Regulation - When the macula densa detects low Na+ concentration in the provisional urine, it causes a cascade of events (see above) that result in aldosterone binding to Principal cells in the collecting tubules and duct of the nephron. Thus, the collecting tubules and duct increase their uptake of Na+, which is then transferred into the blood raising the blood Na+ concentration. Clinical Correlation Diabetes Insipidus - increased water consumption (polydipsia) and increased urination (polyuria) due to defect in ADH effectiveness (hypophyseal tumors, defective receptors). No glucose in urine. Diabetes Mellitus - high concentration of glucose in blood acts as an osmotic diuretic in nephron. Glucose in urine. Urinary System Dr. Lalit P. Singh Page 19 of 23 O. Interstitial cells (Fig. 26) - have endocrine functions. 1. Several types in both cortex and medulla: Include endocrine-like cells which produce erythropoietin, a stimulant of red blood cell production in bone marrow and thromopoietin, a Fig. 26 Interstitial cells. stimulant of platelet production in bone marrow. 2. Other endocrine functions include the hydroxylation of a 25-OH vitamin D3 precursor to the hormonally active form - 1, 25-(OH)2D3. P. Excretory passages - lined with transitional epithelium in minor calyces (Fig. 27), major calyces, renal pelvis, ureter and bladder. Walls gradually thicken as passages near the bladder. Fig. 27 Minor Calyx 1. Renal pelvis and ureter (Figs. 1, 28). (Erlandsen & Magney) a. Mucosa with transitional epithelium (also called urothelium) and fairly dense lamina propria (Fig. 29). b. Muscularis, inner longitudinal and outer circular layers of smooth muscle, another outer longitudinal layer added in lower portion of ureter. c. Adventitia (or, in some regions, a serosa). Urinary System Dr. Lalitt P. Singh Page 20 of 23 Fig. 28 8 Kidney ureter Fiig. 29 Section of ureter (Meyer) (Meyerr) d. Ideentification of o the ureter is aided by its small size (~2 2.8 mm widee, Fig. 28), ttransitional eepithelium, thin n musculariss and being ssurrounded bby adipose tisssue. It is ~30 0 cm long. II. Bladder B (Fig g. 30) A. A Muco osa - transitio onal epitheelium (or euroth helium) thick ker than in ureter that variees from 3-10 layers l with contraaction and disten nsion (Figs. 30, 3 31) 1. Interdigitaated cell bord ders facilitatte Fig. 30 Layers of b bladder (Sobotta) distension. Urinary System Dr. Lalitt P. Singh Page 21 of 23 2. Surface ceells have plaq ques of thickk asymmetriical plasma membranees and fusifo orm vesicles in the apicall cytoplasm which are reserve pack kets of mem mbrane materrial (Fig. 32)). Membranee can fold in nward or reinnsert for disteension. Fig. 31 Urotthelium Fig. 32 EMM of Fusiform vesicles (Erlandsen ( & Magney) (Erlan ndsen & Magn ney) B. B Musccularis - threee layers: lon ngitudinal, ciircular, longgitudinal. Pierceed obliquely by ureters. Circular layyer thickenedd near openin ng of urethraa to form intternal sphinccter. C. C Adven ntitia. III. Urethra U – (I)) Female (Fig. 33) A. A Muco osa 1. Transition nal epithelium m near bladder giv ves way to stratified squamous s wiith patches off stratified orr pseudostraatified colum mnar. Lamina prropria has maany F Fig. 33 Femalle Urethra elastic fibeers. 2. Mucous gllands of Litttré (fewer thaan in male). Urinary System Dr. Lalit P. Singh Page 22 of 23 B. Muscularis - inner longitudinal and outer circular layers of smooth muscle. Much thicker muscularis than in ureter. 1. Internal sphincter of smooth muscle is around origin of urethra from bladder (Fig. 34). Fig. 34 Urethral Sphincter 2. External sphincter of Muscles skeletal muscle arises from urogenital diaphragm. (II) Male Urethra: The size, structure, and function of the male urethra is different from the female urethra. It forms a part of both the urinary and genital systems. It is ~20 cm long while female urethra is ~3-5 cm in length. Male urethra will be examined later together with Male Reproductive System (Fig. 34, left). References: Erlandsen, S.L. & Magney, J.E. Histology Microfiche Atlas, Univ. of Minnesota Press, Minneapolis, 1985 (fiche 9 & 12). Hammersen, F., (Sobotta/Hammersen) Histology A Color Atlas of Cytology, Histology, and Microscopic Anatomy, Urban & Schwarzenberg, Baltimore-Munich, 1980. [Cited in figures as “Sobotta”] Kessel, R.G. & Kardon, R.H. Tissues and Organs: A Text/Atlas of Scanning Electron Microscopy, W.H. Freeman & Co., San Francisco, 1979. Meyer, D. Unpublished Histology Slides, Wayne State University School of Medicine, 1972. Urinary System Dr. Lalit P. Singh Page 23 of 23 Rhodin, J.A.G., Histology A Text and Atlas, Oxford University Press, New York, 1974, Chapter 32. Ross, M.H. & Pawlina, W., Histology (2011, 6th ed., 2015, 7th ed.), Lippincott, Williams & Wilkins, Baltimore, 2011, Chapter 20. Dongkei Cui, Atlas of Histology with Functinal & Clinical Correlations (2011, 1st ed.) Lippincott, Williams & Wilkins, Philadelphia, PA LPS: 11/15/2022