Histology of Urinary System PDF

Histology of Urinary System Fevziye Figen Kaymaz M.D., Ph.D. Prof. of Histology & Embryology [email protected] 1 Learning Goals: 2 Function 1. To clear the blood of nitrogenous and other waste metabol...

Histology of Urinary System Fevziye Figen Kaymaz M.D., Ph.D. Prof. of Histology & Embryology [email protected] 1 Learning Goals: 2 Function 1. To clear the blood of nitrogenous and other waste metabolic products by filtration and excretion 2. To balance the concentration of body fluids and electrolyctes by filtration and excretion 3. To recover by reabsorption small molecules (amino acids, glucose, peptides), ions (Na+, Cl-, Ca2+, PO-3), and water in order to maintain blood homeostasis 3 Endocrine activities: 1. to produces erythropoietin, a stimulant of red blood cell production in bone marrow when blood O2 level is loww; 2. Regulates blood pressure by synthesis and secretion of renin, that initiates the conversion of angiotensinogen (a plasma protein produced in liver) to the active component angiotensin I 3. to activate 1,25-hydroxycholecalciferol , a vitamin D derivative involved in the control of calcium metabolism, to calcitriol. Steroid prohormon vit D initially produce in keratinocytes, hydroxylated in kidneys as an active form 4. Gluconeogenesis; synthesis glucose from noncarbohydrate sources. The rate is equal of liver. 4  Overview of KIDNEY Structure — Retroperitoneal — posterior abdominal cavity — 12th thoracic to the 3rd lumbar vertebrae 5 6 Capsule dense irregular connective tissue, with occasional elastic fibers, and smooth muscle cells. The capsule consists of two distinct layers: – An outer layer of fibroblasts and collagen fibers – An inner layer with a cellular component of myofibroblasts. Kidney. Each kidney is bean—shaped, with a concave hilum where the ureter and the renal artery and veins enter. The ureter divides and subdivides into several major and minor calyces, around which is located the renal sinus containing adipose tissue. Division of the parenchyma into cortex and medulla can also be seen grossly. Attached to each minor calyx is a renal pyramid, a conical region of medulla delimited by extensions of cortex. A renal pyramid with associated cortex constitutes a renal lobe. The cortex and hilum are covered with a fibrous capsule. 7  Each kidney surrounded by 3 layers of CT: Lobe § renal capsule – innermost layer of dense CT Lobule adipose capsule – middle layer §protecting & insulating kidneys § renal fascia – outer layer holding kidneys in place in abdominal cavity § Cortex §Renal corpuscles §Cortical labyrinth §Medullary ray § Medulla § pyramids § renal papillae § renal columns § Pelvis § minor calyces § major calyces § renal pelvis 8  The main function of the kidneys is to filter the blood supplied by the renal arteries branching from the descending aorta. The kidneys receive about 20% of the cardiac output per minute and filter about 1.25 L of blood per minute. All the blood of the body passes through the kidneys every 5 minutes. About 90% of the cardiac output goes to the renal cortex; 10% of the blood goes to the medulla. Approximately 125 mL of filtrate is produced per minute, but 124 mL of this amount is reabsorbed. 1ml released as urine. About 180 L of fluid ultrafiltrate is produced in 24 hours, whereas only 1.5 L is excreted as urine. 9 Renal Cortex 10 1 1 Kidney cortex R: renal corpuscle M: medullary ray Renal corpuscles Blood supply to the kidney. A coronal view (left) shows the major blood vessels of the kidney. The microvascular components extending into the cortex and medulla from the interlobular vessels are shown on the right. Pink boxes indicate vessels with arterial blood and blue indicate the venous return. The intervening lavender boxes and 12 vessels are intermediate sites where most reabsorbed material re—enters the blood. NEPHRON Renal corpuscle Glomerular capillaries Bowman capsule Proximal tubule Loop of henle Distal tubule Cortical nephrons Juxtamedullary nephrons Medullary ray Pyramids Papilla Renal pelvis Outer zone Outer stripe İnner stripe Inner zone 13 Renal corpuscles Vascular pole Urinary pole Bowman’s capsule Bowman’s (urinary)space 14 Renal corpuscles. (a): The renal corpuscle is a small mass of capillaries called the glomerulus housed within a bulbous glomerular capsule. The internal lining of the capsule is composed of complex epithelial cells called podocytes, which. cover each capillary, forming filtration slits between interdigitating processes called pedicels. Blood enters and leaves the glomerulus through the afferent and efferent arterioles respectively. (b): The micrograph shows the major histological features of a renal corpuscle. H&E. X300. (c): Filtrate is produced in the corpuscle when blood plasma is forced under pressure across the filtration membrane of the glomerular capillary wall and through the filtration slits between the pedicels of podocyte processes. (d): The SEM shows the distinctive appearance of podocytes and their processes covering glomerular 15 capillaries. X800 16  Glomerular Basal Membrane between the fenestrated endothelial cells and the podocyte 320-340nm 17 18 Mesangium: mesangial cells and their extracellular matrix The connective tissue component of afferent arteriole replaced by a specialized cell type known as mesangial cells. There are two groups of mesangial cells : 1. Extraglomerular mesangial cells are located at the vascular pole and form part of the juxtaglomerular apparatus. (lacis cells) 2. İntraglomerular mesangial cells are pericyte-like and situated within the renal corpuscle. 19 Function of Mesangial cells Phagocytosis and endocytosis: dispose of normal or pathologic molecule trapped by GBM, keep the ultrafiltrate free of debris Structural support: synthesis extracellular (mesangial) matrix, provide support for the podocytes, support the capillaries of glomerulus where bowman’s capsule doesnot come in contact with capillaries Modulation of glomerular distension: contractile because they have receptors for vasoconstrictors such as angiotensin II and reduce blood flow through the glomerulus. Secretion: produce chemical mediators; IL-1, PGE2, PDGF(platelet derived growth factor) 20  Continuing from Bowmanʼs capsule the remaining parts of the nephron (the tubuler parts) are: Proximal tubule Loop of Henle Distal tubule The tubuler segments of the nephron are named according to; — the course that they take (convulated or straight), — location (proximal or distal) — wall thickness (thick or thin) 21  Proximal Tubule Bowmanʼs space drains into the prox tubule at the urinary pole. At this region the simple squamous epithelium of the parietal layer of Bowmanʼs capsule joins the simple cuboidal epithelium of the tubule. Cuboidal cells have elaborate surface specializations associated with cells engaged in absorption and fluid transport. Diameter is 60µm 22  Prox. tubules has two regions 1. Pars convulata (Prox. convulated tubule)-PCT-: located near renal corpuscle 2. Pars recta (descending thick limb of Henleʼs loop): straighter portion. Descends in medullary rays in the cortex then in the medulla continuous with the loop of Henle.. 23 2 4 Features of cuboidal cells in PCT: Brush border: The cells have a prominant striated border (or brush border) of tall microvilli which almost completely fill the lumen. A system of intermicrovillar caveolae known as apical canaliculi that extend into the apical cytoplasm. Junctional complex: consisting of a narrow tight junction that seals off the intercellular space from the lumen of the tubule. A zonula adherens that maintains the adhesion between neighboring cells. Plica or folds: located on the lateral surfaces of the cells which are large flattened processes, alternating with similar processes of adjacent cells. Extensive interdigitation of basal processes of adjacent cells Basal striations: consisting of elongate mitochondria concentrated in the basal processes and oriented vertically to the basal surface. PCT is the initial and major site of reabsorption PCT reabsorbs about 150L of fluid per day or about 80% of the ultrafiltrate. 67 to 80% of Na+, Cl- and water is resorbed from the glomerular filtrate and transported into the connective tissue stroma by cells of proximal tubule. 25  Prox straight tubule = thick descending limb of the loop of Henle = pars recta PST are not specialized for absorption as PCT. Less well developed brush border With fewer and less complex lateral and basal-lateral processes Mitochondria are smaller Fewer apical invaginations and endocytotic vesicles Fewer lysosomes 26 2 Thin segment of Loop of Henle 7 Thin segment of Loop of Henle have three regions: 1. Descending thin limb (pars recta of prox tubule) 2. Henleʼs loop 3. Ascending thin limb (pars recta of distal tubule) Diameter is about 20µm Composed of squamous epithelial cells The nuclei of the cells bulge into the lumen of the tubule. In paraffin sections, these limbs resemble capillaries in cross sections. They may be distinguished from capillaries in their epithelial lining cells. They are slightly thicker, their nuclei stain less densely and their lumina contain no blood cells.  Distal Tubule DT has three regions: 1. Pars recta (the ascending thick limb of loop of Henle) ( distal straight tubule) — Distal straight tubule includes 2. The macula densa medullary and cortical portions, 3. Pars convoluta (distal convoluted located in medullary rays. tubule — 30 to 40 µm in diameter — In routine histologic preparations, large cuboidal cells stain lightly with eosin and the lateral margins of the cells are indistinct. — Low cuboidal cells have apically located, round to oval nuclei and a few club shaped short microvilli. — Lateral interdigitation of the cells are not elaborate as in PCT — Basal interdigitations (folds) are extensive and number of mitochondria is grater than the PCT — They form highly efficient zonulae occludentes with their neigboring cells. 28 2 9 Distal convulated tubule Located in the cortical labyrinth Because DCT are shorter than PCT, in sections of the kidney we mostly examine PCT. The ratio is 7:1 Short, 25 to 45 µm diameter. In paraffin sections the lumina are wide open, the granular cytoplasm of low cuboidal lining epithelium is paler than those of prox convulated tubules, because the cells are narrower, more nuclei are apparent in tubular cross section. DCT cells have pale cytoplasm with a few apical microvilli. Nuclei are round and apically located, having 1 or 2 dense nucleoli. Mitochondria are not numerous and the basal interdigitations are not as extensive as asending thick limb of loop of Henle. DCT is impermeable to water and urea (in response to aldesteron resorb Na and Cl  Juxtaglomerular Apparatus It has three components: 1. Macula densa of the distal tubule 2. Juxtaglomerular cells of the adjacent afferent glomerular arteriole 3. Exraglomerular mesangial cells (Polkissen, lacis cells) Regulates blood pressure by activating renin – angiotensin – aldosterone system Sensor of blood volume and tubular fluid composition 30 3 1 Macula Densa As the ascending thick limb of Henle passes near its own renal corpuscle, it lies between the aff and eff glomerular arterioles. This region of DT is called macula densa. Because the cells of MD are tall and narrow, the nuclei of these cells appear to be much closer together than those of the remainder of DT. With the electron microscope these cells demonstrate numerous microvilli small mitochondria and an infranuclearly located Golgi apparatus. Monitor the Na concentration in the tubuler fluid, regulate the glomerular filtration rate and the release of renin from jg cells 3 2 Juxtaglomerular (JG) cells. JG cells are modified smooth muscle cells located in the tunica media of the afferent (sometimes eff arteriole) glomerular arterioles The nuclei of these cells are round JG cells contain specific granules containing proteolitic enzyme renin. JG cells require special stains to reveal the secretory vesicles in the light microscope. Angiotensin-converting enzyme (ACE), angiotensin I and angiotensin II are also present in these cells. The basal lamina is absent between JG cells and the cells of the macula densa, permitting intimate contact. 3 3 Extraglomerular mesangial cells: Occupy the space bounded by the aff arteriole, macula densa, eff arteriole and vascular pole of the renal corpuscle. Contigous with the intraglomerular mesangial cells. 3 4 Collecting tubules Collecting Ducts Collecting tubules are not part of the nephron. They have different embryological origin. Collecting tubule: composed of simple cuboidal epithelium. Collecting ducts: convey and modify the ultrafiltrate from the nephron to the minor calyces.  Collecting ducts are impermeable to water, however in the presence of antidiuretic hormone (ADH) they become permeable to water. 35 36  The apex of renal papilla is perforated by 20 or so openings of the ducts of Bellini; this sieve-like region is known as the area cribrosa. The cells of the collecting ducts gradually become taller as the ducts pass from the outer to inner medulla and become colunmar in the region of the renal papilla. The number of dark cells gradually decrease until none are present in the ducts as they approach the papilla 37  EXCRETORY PASSAGES OF URINE All excretory passage, except urethra, have the same general organisation: - T. Mucosa (lined by transitional epithelium) - T. Muscularis - T. Adventitia (or in some regions T. Serosa) 38  Urine leave the collecting ducts at the area cribrosa, and enters a series of structures that are specialized for its storeage and passage to the extrerior of the body The urine flows to minor calyx, major calyx, and the renal pelvis and leaves each kidney through the ureter to the urinary bladder where it stored. The urine is finally voided through the urethra. 39  Transitional epithelium (urothelium) lines the calyces, ureters, bladder and the initial segment of the urethra İmpermeable to water and salts The epithelium begins in the minor calyces as two cell layers and increases to four – five layers in the ureter. Six or more layers in empty bladder. When the bladder is distended three layers can be seen. This epithelium has ability to accommodate to distension. 40  The cells in the distended bladder, the large surface cells and those in the layer below, flatten and unfold to accommodate the increasing surface area. In routine histologic sections obtained from empty bladder the surface epithelial cells are usually cuboidal and bulge into the lumen. They are described as “dome shape” cells because of the curvature of the apical surface. 41  A dense collagenous lamina propria underlies the urotheliım. No muscularis mucosae and no submucosal layer is observed in their walls. T. Muscularis: Two layers of smooth muscle lie beneath the lamina propria: 1. Longitudinal layer; the inner layer, arranged in a loose spiral. 2. Circular layer; the outer layer, arranged in a tight spiral Arragement of smooth muscle is opposite the muscularis externa of the intestinal tract. The smooth muscle of the urinary passage is mixed with connective tissue, so that it forms parallel bundles rather than pure muscular sheets. Peristaltic contraction of the smooth muscle move the urine from the minor calyces through the ureter to the bladder 42  Calyces 3 urine leave renal pyramid from renal papilla, ducts of Bellini at the area cribrosa the apex of the pyramid and minor calyx is covered by transitional epithelium as many as four minor calyces may deliver their urine to a major calyx. The major calyces are similar to minor calyces Deep into the lamina propria is a thin smooth muscle layer. This muscular layer propels the urine into a major calyx expanded prox region of the ureters, the renal pelvis. The walls of the secretory passage thicken from the minor calyces to the urinary bladder.  Ureter 4 ureter conducts urine from the renal pelvis to urinary bladder. It is approximately 3 to 4 mm in diameter and 25 to 35 cm long. The distal part of the ureter enters the urinary bladder and follows an oblique path through the wall of the bladder. — Urothelium –transitional The mucosa of the ureter epithelium- three to five has several folds, which cell layers in thickness project into the lumen lines the luminal surface when the ureter is empty of the wall of the ureter. but are absent when the ureter is distended. — Lamina propria is a layer of dense irregular fibroelastic connective tissue. T. muscularis of the ureter is composed of two layers for the prox two thirds. Inner longitudinal and outer circularly arranged smooth muscle cells. In the lower third near the urinary bladder a third muscle layer is added. Smooth muscle fibers are oriented longitudinally. the muscular fiber orientation in the lower one third of the ureter is outer long., middle circular, inner long. 45  muscular contraction of the ureteric wall establishes peristalsis-like waves that convey urine to the urinary bladder. a valve like flap of mucosa hangs over each ureteric orifice, preventing regurgitation of urine from the bladder back into the ureters T. Adventisia: LCT, The adipose tissue, vessels, and nerves form the adventitia of the ureter. The ureter is embedded in the retroperitoneal adipose tissue. 46  muscular organ that temporarily Urinary bladder §stores urine prior to “micturition” § Lined with mucosa of transitional epithelium with rugae Muscularis of 3 layers of §smooth muscle known as “detrussor muscle” § Internally have “trigone” – triangular area formed by openings of ureters & urethra. The mucosa of the trigone is always smooth and is never thrown into folds. The embryonic origin of the trigone (from mesonephric duct) differs from that of the remainder of the bladder (cloaca). 47 8 The mucosa acts as an osmatic barrier between the urine and the lamina propria. The mucosa of the bladder is arranged in numerous folds, which disappear when the bladder distended. During distention the large round dome shaped cells of transitional epithelium The lamina propria of the bladder may be sudivided into two layers: More superficial; dense, irregular collagenous connective tissue Deeper; loose layer of connective tissue composed of a mixture of collagen and elastic fibers. Lamina propria contains no glands except at the region surrounding the urethral orifice, where mucous glands may be found. They secrete a clear viscous fluid that apparently lubricates the urethral orifice. 9 T. muscularis of the urinary bladder is composed of three layers of smooth muscle. (detrusor muscle) Layers can be separated only in the region of neck of the bladder. detrusor muscle are less regularly arranged than the tubuler portions of the excretory passage. The muscle and the collagen bundles are randomly mixed. The middle sircular layer forms the internal sphincter muscle around the internal orifice of urethra. Contraction of the detrusor muscle of the bladder compress the entire organ and forces the urine into urethra  Urethra § Urethra is the fibromuscular tube that convey urine from the urinary bladder to the exterior through the external urethral orifice § Anatomically different in men & women §Inner urethral sphincter of smooth muscle; external urethral sphincter ; As the urethra pierces the perineum, §skeletal muscle fibers form the external sphincter muscle surrounding the urethra. This muscle permits voluntary control of micturition. 50 In the male; it is longer (15 to 20 cm) than the female and has a dual function: It serves as the terminal duct for both urinary and genital system; Acting as a route for urine as well as for semen : 51 In the female; About 4 to 5 cm long, 5 to 6 mm in diameter It extends from the urinary bladder to the external urethral orifice just above and anterior to the opening of the vagina and posterior to the clitoris. The lumen is collapsed except during micturition.. 52