Urinary System Histology (PDF)

XY2141. HISTOLOGY. URINARY SYSTEM Dr Viktoriia Yerokhina, Lecturer in Medical Sciences [email protected]  LEARNING OUTCOMES HIST.22 - Urinary HIST.22.01 - Describe the anatomy of the kidney as seen in surface and hemisected...

XY2141. HISTOLOGY. URINARY SYSTEM Dr Viktoriia Yerokhina, Lecturer in Medical Sciences [email protected]  LEARNING OUTCOMES HIST.22 - Urinary HIST.22.01 - Describe the anatomy of the kidney as seen in surface and hemisected view HIST.22.02 - List the segments of a nephron HIST.22.03 - Prepare a labelled diagram of a renal corpuscle HIST.22.04 - Describe the arrangement of podocytes and their association with glomerular capillaries HIST.22.05 - List the components of the filtration barrier HIST.22.06 - List the factors that contribute to ultrafiltration HIST.22.07 - Locate the mesangium & describe the arrangement of mesangial cells and capillaries HIST.22.08 - Name 2 components of the juxtaglomerular apparatus and give their location & function HIST.22.09 - Compare the epithelial lining of the proximal tubule, thin segment and distal tubule HIST.22.10 - Describe the location and structure of collecting tubules and collecting ducts HIST.22.11 - Discuss the composition of interstitial tissue HIST.22.12 - Describe the arrangement of blood vessels in the kidney HIST.22.13 - Give the location and describe the structure of the ureter as seen in cross section HIST.22.14 - Describe the wall of the urinary bladder, including the features of transitional epithelium HIST.22.15 - Compare the male and female urethra. 2  INTRODUCTION Urinary system consists of a complex of: paired (kidney, ureters) non-paired organs (urinary bladder, urethra). 3  FUNCTIONS OF THE URINARY SYSTEM Regulation of water, inorganic ion and acid-base balance; Removal of metabolic waste products, chemicals from the blood and their excretion in the urine; Regulation of blood volume and blood pressure Production of hormones/enzymes: o Erythropoietin, which controls erythrocyte production in red bone marrow when the blood O2 level is low; o Renin cleaves circulating angiotensinogen to release angiotensin I. o Hydroxylation of 25-OH vitamin D3 Gluconeogenesis during starvation making glucose from amino acids to 4 supplement this process in the liver.  KIDNEY Each kidney is a bean-shaped organ covered by a capsule. Capsule consists of collagen, elastic fibers and smooth muscle cells. Medial border of kidney has hilum through which vessels and nerves enter the kidney. At hilum, renal pelvis (space) continues as ureter. Space that occupies vessels, nerves, and renal pelvis at hilum of kidney is called renal sinus. Renal pelvis is divided into two major calyces (upper and lower). Each major calyx is divided into a number of cup-shaped minor calyces that show conical projections of kidney called papillae. 5  KIDNEY STRUCTURE On examination with naked-eye, kidney shows the following structures: – Outer cortex – Inner medulla Medulla consists of 8-15 medullary pyramids. From the base of each pyramid the medullary rays penetrate the cortex. Apex of the medullary pyramid is known as renal papilla, projects into a minor calyx. Area cribrosa is perforated area at the tip of renal papilla because of collecting ducts openings. Renal columns represents cortical tissue that is extended between adjacent renal pyramids Cortex is the peripheral part lying between the capsule 6 and the bases of renal pyramids.  KIDNEY Renal lobe: one pyramid and part of the cortex overlying together. Renal lobule: a medullary ray with its surrounding cortex. 7  NEPHRON Nephron is the structural and functional unit of kidney. Each kidney contains approximately 1-3 millions of nephrons. Each nephron consists of: o renal corpuscle, o tubular system. 8  TISSUE SECTIONING In histology books, there will be various types of sectioning and it is your responsibility to be able to recognize each tissue type no matter the type of section presented.  RENAL CORPUSCLE/MALPIGHIAN CORPUSCLE Renal corpuscle is a spherical structure. It consists of: Glomerulus: a tuft of blood fenestrated capillaries. Bowman's (renal/glomerular) capsule: a cup-like double-layered covering of glomerulus. Urinary/Bowman's space: a space between two layers of Bowman's capsule (urinary space). 10  RENAL CORPUSCLE (MALPIGHIAN CORPUSCLE) Every kidney contains about 1-3 million of renal corpuscles, but not all of them are active at every moment Poles of the corpuscle: Vascular pole - point of entry and exit of afferent and efferent arterioles Urinary pole - point of exit of the proximal tubule from the Bowman’s capsule. 11  GLOMERULUS Glomerulus – bundle of about 30 interconnected anastomosing fenestrated (perforated) capillaries with pores between the endothelial cells. Function: blood filtering, so the efferent arteriole already contains blood after the removal of primary urine. 12 Kidney. Renal corpuscles 13  SEM. RENAL CORPUSCLES AND ARTERIOLES Branches of arterioles (blue) supply blood to renal corpuscles. Blood enters the glomerulus (yellow) through the afferent arteriole, passes through loops of fenestrated capillaries (tuft), and then exits through the efferent arteriole. 14 *Glomerulus denotes only the glomerular capillary network of the renal corpuscle. It is sometimes erroneously mistaken for the renal corpuscle itself.  BOWMAN’S CAPSULE Initial part of the nephron, formed by two sheets, with the urinary space in between: 1. Visceral layer – inner sheet formed by podocytes, adjacent to the capillary loops 2. Parietal layer – outer sheet, adjacent to the whole renal corpuscle formed by simple squamous epithelium. Urinary space – collects primary urine (ultrafiltrate) after glomerular 15 filtration.  PODOCYTES Form visceral layer of the Bowman’s membrane. Specialized epithelial cell, terminally differentiated. Podocytes have a cell body from which several primary processes arise. Each primary process gives secondary processes (pedicels). Between the pedicles there are spaces termed filtration slits. Filtration slits are covered by an ultrathin filtration slit diaphragm that spans the filtration slit above the glomerular basement membrane (GBM). 16 SEM. PODOCYTES 17  Glomerular basement membrane (GBM) GBM is a thick (about 300 nm) membrane between the fenestrated endothelial cells and the podocytes. Layers of GBM: Central electron dense layer (lamina densa) - a network of collagen (type IV) physical barrier. Inner and outer electron lucent layers (lamina rara interna and externa) - contain the glycosaminoglycan heparan sulfate  bears the negative charges. GBM is, therefore, both a physical barrier and an electrical barrier to the passage of large molecules. 18  GLOMERULAR FILTRATION BARRIER Filtering blood from the glomerulus to produce the primary urine, which leaves the renal corpuscle into the renal tubules. It consists of 3 layered components: 1. Fenestrated capillary endothelium, 2. Glomerular basement membrane (GBM), 3. Filtration slit diaphragms between pedicels. 19  RESULT OF THE FILTRATION Glomerular filtration is the first stage of the urine production. Normally about 20% of the blood plasma entering a glomerulus is filtered into the capsular space. Initial glomerular filtrate has a chemical composition similar to that of plasma except that it contains very little protein. Glomerular filter blocks filtration of most plasma proteins, but smaller proteins, including most polypeptide hormones, and amino acids are removed into the filtrate. 20 GLOMERULAR FILTRATION BARRIER 21 GLOMERULAR FILTRATION BARRIER Cells and large or negatively- charged molecules, e.g., proteins, cannot cross the filtration barrier and remain within the blood (size and charge selectivity). 22 EM. GLOMERULAR FILTRATION BARRIER 23  MESANGIUM Glomerular capillaries are held together by mesangial cells and their extracellular matrix. Mesangial cells work similar to pericytes of capillaries and are embedded in basal lamina of capillaries. FUNCTIONS: Phagocytosis and endocytosis; Structural support for the podocytes; Secretion of the variety of molecules such as interleukin 1 (IL-1), PGE2, and platelet- derived growth factor, which play a central role in response to glomerular injury. Mesangial cells have angiotensin II receptors and these cells help in regulation of blood flow through glomerulus. 24 MESANGIUM 25  CLINICAL CORRELATION – GLOMERULAR DISEASES Renal glomeruli excrete urinary substances and excess water as an ultrafiltrate into the urine by selectively filtering the blood. Any damage to the glomeruli disrupts the filtration process and results in the appearance of blood components (proteins and RBC) in the urine. Glomerular damage is commonly caused by immune-mediated processes, which often lead to glomerulonephritis. Non-inflammatory causes, such as metabolic disease (e.g., diabetes, amyloidosis), can also result in significant damage to the glomeruli. Pathophysiology of glomerular diseases is complex; most patients present with either nephritic syndrome (low-level proteinuria, microhematuria, oliguria, and hypertension) or nephrotic syndrome (high-level proteinuria and generalised edema). All glomerular diseases can progress to acute or chronic renal failure. Quick diagnosis and immediate initiation of therapy are required to prevent26 irreversible kidney damage.  After passing the glomerulus, the ultrafiltrate (now referred to as “tubular fluid”) flows through the tubular system → reabsorption and secretion of plasma components (approx. 99% of the ultrafiltrate is reabsorbed into the bloodstream) → urine concentration. Following stages of the urine production: 2) tubular reabsorption, 3) secretion. 27  TUBULAR PART Consist of: Proximal thick segment: proximal convoluted tubule (PCT), proximal straight tubule (PST) Thin segment consist of: descending limb, ascending limb Distal thick segment: distal straight tubule (DST), distal convoluted tubule (DCT). 28  LOOP OF HENLE Loop of Henle = end of the proximal straight tubule + descending limb of the thin tubule + ascending limb of the thin tubule + distal straight tubule. Descending limb, the loop itself, and part of the ascending limb of the loop of Henle are narrow and thin walled  thin segment of the loop. Upper part of the ascending limb has a larger diameter and thicker wall  thick segment. 29  TYPES OF NEPHRONS 1) Cortical (subcapsular, superficial) nephrons (80%); Glomeruli are located high in the cortex, Have short loops. Glomeruli function under the high pressure and actively participate in formation of glomerular ultrafiltrate. 2) Juxtamedullary nephrons (20%); glomeruli are located near the corticomedullary junction, have very long Henle’s loops, extending deep into the medulla. Glomeruli function under low pressure and don’t play the important role in a process of a filtration. This type is essential to the urine-concentrating 30 mechanism and dilution of urine.  TUBULES OF THE NEPHRON. PROXIMAL SEGMENT a) proximal convoluted tubule - PCT, b) proximal straight tubule (thick descending limb) - PST, Proximal segment is lined by simple cuboidal epithelium. Apical portions of epithelial cell have numerous microvilli  brush border  increase surface area. Basal portions have membrane invaginations; mitochondria are concentrated between them and arranged parallel to the long axis of the cell  basal striations or basal labyrinth). 31  FUNCTION OF PROXIMAL SEGMENT Proximal tubule is the site of initial changes of the primary urine to the definitive urine. Substances the body could use in its metabolic processes are reabsorbed. Proximal tubule cells absorb proteins via pinocytosis, bigger protein molecules are cleaved to amino acids using an array of enzymes on the brush border. Glucose passes via facilitated diffusion the same way as amino acids. Sodium ions are absorbed via ion pumps, followed by water based on the concentration gradient. In addition to absorption the cells of the proximal tubule ensure tubular “filtration” of waste products from the blood, e.g. drugs or creatinine.  FUNCTION OF PROXIMAL SEGMENT Proximal segment is the major site of reabsorption. PCT also reabsorb all glucose and amino acids and most HCO3–, Na+, Cl–, PO4, K+, H2O, and uric acid. Isotonic absorption. a) PCT recovers most of the fluid from the ultrafiltrate. b) PST recover the remaining glucose that escaped recovery in the PCT before it enters the thin segment of the loop of Henle. They are equipped with high-affinity Na+ glucose cotransporters that simultaneously absorb Na+ and glucose from the lumen of the tubule. 33  LOOP OF HENLE Part of the countercurrent exchange system that functions in concentrating urine. Parts: o Thin descending limb of the loop of Henle - formed by simple squamous epithelium. o Thick ascending limb of the loop of Henle – cell become taller, have tight junctions (impermeable to water). 34  DIFFERENCES BETWEEN THIN DESCENDING AND ASCENDING LIMBS OF THE LOOP OF HENLE The ultrafiltrate that enters the thin descending limb is isosmotic, whereas the ultrafiltrate leaving the thin ascending limb is hyposmotic to plasma. This change is achieved by reabsorbing more salts than water. DIFFERENCES: Thin descending limb is highly permeable to water due to the presence of aquaporins that allow for free passage of water (passively reabsorbs H2O via medullary hypertonicity). This limb is much less permeable to Na+ and urea; Thin ascending limb is highly permeable to Na+ and Cl- due to the presence of Na+/K+/2Cl- cotransporters in the apical plasma cell membranes. Further, the thin ascending limb is largely impermeable to water. Indirectly induces paracellular reabsorption of Mg2+ and Ca2+ through ⊕ lumen potential generated by K+ back leak.  DISTAL THICK SEGMENT a) distal straight tubule, b) distal convoluted tubule Structure in general: Lined by simple cuboidal epithelium. Apical portion has no brush border. Basal portion has basal striations (basal labyrinth) 36  Distal straight tubule DST is part of the ascending limb of the loop of Henle. DST, like the ascending thin limb, transports ions from the tubular lumen to the interstitium. Apical cell membrane has electroneutral transporters (synporters) that allow Cl- , Na , and K+ to enter the cell from the lumen. Epithelial cells lining the thick ascending limb produce a protein called uromodulin (Tamm- Horsfall protein) that influences NaCl reabsorption and urinary concentration ability. 37  DISTAL CONVOLUTED TUBULE DCT is about one third long as that of PCT. DCT is lined by simple cuboidal epithelium without brush border Resorption of ions: Na+, Cl-, Mg2+and Ca2+ Impermeable to H2O Decreases ultrafiltrate osmolality PTH increases vitamin D3 production → ↑ Ca2+ and Na+exchange → ↑ Ca2+reabsorption Angiotensin II increases Na+ reabsorption ANP Aldosterone 38 DCT works under the control of aldosterone in increasing the absorption of Na+ ions. Urine passes: distal convoluted tubules  collecting tubules  collecting ducts  papillary duct of Bellini, which opens at the apex of each renal papilla. Collecting ducts possess aquaporins and antidiuretic hormone (ADH)-regulated water channels that regulate water reabsorption. 39  COLLECTING DUCT SYSTEM Lined by simple cuboidal epithelium without brush border but it becomes columnar as the size of duct increases Consists of 2 types of cells: Light – principal cells Dark intercalated 40  SYSTEM 1) Light / bright cells are principal cells of this system with electron-lucent cytoplasm and few organelles, Possess aquaporin-2 channels that are sensitive to antidiuretic hormone (in case of water content decrease in the body; in case of water excess, it is not reabsorbed and is released in urine) Sensitive to ANP (atrial natriuretic peptide) based on its concentration, it inhibits reabsorption of sodium and chloride ions); Contain aldosterone receptors Function: reabsorption Na+ and water, secrete K+. 2) Dark intercalated cells with microvillous surface and mitochondria in the cytoplasm; α-cells - secret H+; β-cells - secret HCO3– Function: have a role in the resorption of hydrogen-carbonates exchanged for chloride anions. 41 SYSTEM 42  HORMONAL REGULATION – ANTIDIURETIC HORMONE Antidiuretic hormone (ADH; vasopressin) Regulation of plasma osmolality Mediated by V2 Insertion of aquaporin channels in the principal cells of the renal collecting duct and DCT Results in increased water reabsorption Regulation of blood pressure Mediated by V1 receptors  vasoconstrictive effects at higher levels Increase of urea reabsorption in the collecting duct: facilitates urine concentration. 43  HORMONAL REGULATION - ALDOSTERONE Mechanism of action: aldosterone binds to intracellular mineralocorticoid receptors in the distal tubule and collecting duct of the kidney, inducing protein synthesis and following changes: These aldosterone-induced changes produce a concentration gradient → Na+ reabsorption → water reabsorption and K + secretion into the urine. Ultimately, these effects → ↑ blood pressure, hypokalemia, and ↑ pH level. 44  STAGES OF THE URINE FORMATION 1. Glomerular filtration involves the(SUMMARY) transfer of soluble components, such as water and waste, from the blood into the glomerulus. 2. Reabsorption involves the absorption of molecules, ions, and water that are necessary for the body to maintain homeostasis from the glomerular filtrate back into the blood. 3. Secretion involves the transfer of hydrogen ions, creatinine, drugs, and urea from the blood into the collecting duct, and is primarily made of water. 45  INTERSTITIAL CELLS The space between the tubules and blood vessels form the renal interstitium – CT with fibroblasts, interstitial dendritic cells, collagen fibers, and ground substances rich in proteoglycan. This tissue increases in amount from the cortex (7% of the volume) to the medulla and papilla (more than 20%). In the cortex there are two types of interstitial cells: Cells that resemble fibroblasts, Macrophages. In medulla: Principal interstitial cells resemble myofibroblasts. * It has been held that interstitial cells produce prostaglandins, but it now appears that prostaglandins 46 are produced by epithelial cells of collecting ducts  KIDNEY BLOOD SUPPLY In cortical nephrons the efferent arteriole has a smaller lumen than the afferent arteriole. This inequality serves to promote the filtration pressure in the glomerulus. In juxtamedullary nephrons the efferent arteriole is of the same caliber as the afferent. Cortical nephron: Efferent arteriole has a smaller lumen than the afferent arteriole 49  KIDNEY BLOOD SUPPLY Efferent arterioles from cortical glomeruli lead into a peritubular capillary network that surrounds the local uriniferous tubules. Efferent arterioles from juxtamedullary glomeruli descend into the medulla alongside the loop of Henle; and give rise to the descending vasa recta, which together with the ascending vasa recta are involved in the countercurrent exchange system. 50  ERYTHROPOIETIN Erythropoietin (EPO) acts on the bone marrow and regulates red blood cell formation in response to decreased blood oxygen concentration. EPO is synthesised by endothelial cells of the peritubular capillaries in the renal cortex or interstitial cells around proximal tubules and acts on specific receptors expressed on the surface of erythrocyte progenitor cells in the bone marrow. 51  COUNTERCURRENT MULTIPLIER SYSTEM Countercurrent multiplier system creates hyperosmotic urine. It involves: Loop of Henle, Vasa recta, Collecting duct. 1. NaCl is actively transported from the tubular fluid in the ascending limb into the interstitial space. 2. The interstitium becomes hypertonic. This allows water to follow a gradient and move passively from the tubular fluid with a lesser osmolarity to the interstitium with a higher osmolarity 3. Continuous production of urine → continuous movement of water from the tubular fluid into the interstitium → steady increase of the osmotic gradient → significant increase in the amount of water reabsorbed in the descending limb. 52 *The term countercurrent indicates a flow of fluid in adjacent structures in opposite directions. * Osmosis is the spontaneous net movement of solvent molecules through a semi-permeable membrane into a region of higher solute concentration, in the direction that tends to equalize the solute concentrations on the two sides.  JUXTAGLOMERULAR APPARATUS (JGA) Regulates the systemic blood pressure and plasma sodium concentration by activation of the renin-angiotensin-aldosterone system. JGA is the modification of the DCT and the afferent arteriole at the region of their contact. JGA consists of 3 components: 1) Macula densa – ‘dark spot’, 2) Juxtaglomerular cells, 3) Extraglomerular mesangial cells (also known as lacis or Goormaghtigh cells or Polkissen cells). 53  JUXTAGLOMERULAR APPARATUS 1. Macula densa - columnar cells in the wall of the distal convoluted tubule. They are sensitive to the ionic content and water volume (osmoreceptors). Low water volume  macula densa produce signals  promote renin secretion by juxtaglomerular cells. 2. Juxtaglomerular cells are specialized smooth muscle cells in the tunica media of the afferent (and, sometimes, efferent) arteriole. The cytoplasm of these cells contains granules of the enzyme renin. 3. Extraglomerular mesangial cells (also known as Goormaghtigh cells) form a conical mass between the afferent and efferent arterioles. cells are flat and elongated with cytoplasmic processes. they transfer a signal from the macula densa to the arterioles and secrete renin. 54 Renin-angiotensin-aldosterone system 55  URINARY PASSAGES Calyces, renal pelvis, ureter, and bladder have practically the same basic histological structure. Wall of these organs consists of 3 layers: I. Mucosa II. Muscularis III. Adventitia Mucosa consists of: 1) transitional epithelium having 4 or 5 layers of cells; 2) lamina propria which consists of loose CT. Muscularis consists of bundles of smooth muscle cells with intervening CT - the inner layer is longitudinal, the middle layer is circular, outer is longitudinal. Adventitia consists of loose CT with collagen and elastic fibers. Upper part of the bladder is covered by the serous peritoneum. 56  TRANSITIONAL EPITHELIUM (UROTHELIUM) Transitional epithelium lines the calyces, ureters, bladder, and the initial segment of the urethra. Transitional epithelium is essentially impermeable to salts and water. The luminal surface of the transitional epithelium is covered by rigid urothelial plaques containing crystalline protein uroplakins  barrier. Layers of transitional epithelium: 1. Basal row – multi-wall (polyhedral) basal cells 2. Middle row – pear-shaped cells 3. Surface row – umbrella cells, some of which gradually lose contact with the basement membrane, thereby becoming a separate layer. 57  TRANSITIONAL EPITHELIUM (UROTHELIUM) Urothelium ! Umbrella cells may change their shape according to fullness of the organ. 58  URINARY PASSAGES Ureter conducts urine from the renal pelvis to the urinary bladder. It is lined by transitional epithelium, underlying smooth muscle arranged in 3 distinct layers, and connective tissue adventitia. Urinary bladder is also lined by transitional epithelium and possesses many mucosal folds, except in the trigone region. Its muscular wall is thick and well developed and forms the detrusor muscle. 59 Ureter Urinary bladder  Urethra Urethra conveys urine from the urinary bladder to the external urethra orifice. Female urethra is short and lined by: transitional epithelium (upper half), pseudostratified columnar epithelium (lower half), stratified squamous epithelium (before its termination). 60  Male urethra Male urethra is much longer than the female and is divided into three regions: prostatic urethra (lined by transitional epithelium), short membranous urethra that pierces the external urethral sphincter (stratified or pseudostratified columnar epithelium), long penile urethra (pseudostratified columnar epithelium). 61  The History of Histology The Italian microscopist Marcello Malphigi (1628-1694) discovered renal corpuscles and tubules. Freidrich Henle (1809-1885) from Germany contributed to the study of the kidney, and the thin, looped part of the nephron bears his name. The English histologist Sir William Bowman (1816-1892) identified the capsule of the renal corpuscle - Bowman’s capsule. 62 MCQ FOR SELF-CONTROL https://forms.gle/TdcdQDiQNhx2dher6 References