U27. Urinary Organs PDF - Morphology and Functions

Module I UAB MorphoPHEN UNIT 27: URINARY ORGANS L. d’Angelo There are significant differences between mouse a...

Module I UAB MorphoPHEN UNIT 27: URINARY ORGANS L. d’Angelo There are significant differences between mouse and human urinary systems. Mice have unipapillary kidneys, while humans possess pluri-papillary kidneys. Characteristic Mice Humans Nephrogenic period 11 days 30 weeks Nephron number 14,000 1 million Ureter growth Branching Branching/non-branching program Nephron connection Arcades None Lobes Single Multiple For those interested in the genitourinary (GU) apparatus, the GUDMAP (https://www.gudmap.org/) website is an excellent resource. The kidney is one of the most vascularized organs in the body, following the brain. Its primary function is to filter the organic components of the blood and produce urine. The kidney also plays a crucial role in regulating pH and blood pressure (high blood pressure often necessitates increased diuresis), control of electrolites (K+, Ca2+…) that influence cardiac activity and bone structure, and blood formation. The primary actors within the urinary system are the kidneys, ureters, urinary bladder, and urethra. It's important to note that the urethra is shorter in females. 1 Module I UAB MorphoPHEN 1. Kidney. The kidneys are paired organs, positioned in the retroperitoneal region in the upper mid-abdomen, located dorsally in the roof of the abdominal wall, on both sides of the vertebral column. The right kidney is located more cranially than the left kidney and contacts the caudate lobe (ppt right lobe) of the liver (renal impression). Left kidney is more caudal. The kidneys are reddish-brown in color and described as «bean» shaped. Adipose capsule: surround both kidneys and functions as a protective layer. Often surrounded by white adipose tissue with pockets of brown adipose tissue within the pelvis and occasionally surrounding the capsule. Parts in the kidney: - Dorsal face, which contacts the roof of the abdomen. - Ventral face that contacts the abdominal viscera. - The cranial and caudal extremities of the kidneys, connected by a lateral convex border. - In the concave medial border is situated the renal hilus. It is through the hilum that the ureter, blood vessels, and nerves enter and leave the kidney. Mature mouse kidney weight varies considerably with age, breed, husbandry, and especially gender and is approximately 1.15 2.25% of body weight with males having greater kidney weights than females. 2 Module I UAB MorphoPHEN 1.1. Macroscopical division of the kidney: Fibrous capsule: Externally it is covered by the fibrous capsule, a sheet of dense connective tissue surrounding the renal parenchyma. It is a very good place for implantations, (subcapsular implantations). Parenchyma: - Cortex: the most external zone. - Medulla: the internal zone of the parenchyma. The renal medulla is divided into renal pyramids. o The base of the renal pyramids contacts the renal cortex. o The vertex of the renal pyramids contacts the renal pelvis. There we can find the renal papilla: pyramid shaped distal portion of the inner medulla, which, makes prominence in the renal pelvis , occupying almost two thirds of its volume Renal lobe: one renal pyramid and its associated renal cortex. All the renal lobes finish by draining into the renal papilla, which in the case of the mouse (!) is unique (unipapillary), although humans have 6-7 renal papilla (pluripapillary). The renal lobes are not visible neither internally or externally, which gives a smooth outer surface to the kidney. 3 Module I UAB MorphoPHEN 2. Microscopical topography of the kidney: The mouse kidney can be further divided into five topographic areas, which can be distinguished histologically and these include: 1. Cortex 2. outer stripe of the outer medulla 3. inner stripe of the outer medulla 4. inner medulla 5. papilla The inner portion of the medulla (M ) is the renal papilla, which extends into the renal pelvis and ureter (U). Whenever possible, toxic renal responses should be classified on the basis of structure and topographical location. The mouse cortex (C) has cone shaped cortical labyrinths and medullary (M) rays that extend from the outer medulla, which is divided into an outer (OS) and inner stripe (IS) 2.1. Nephron: Nephron is the morpho-functional unit of the kidney. It is composed of: Glomerular capsule (Bowman capsule), Proximal convoluted and straight tubule, Descending and ascending loops of Henle Straight distal tubule. Macula densa. Convoluted distal tubule. 4 Module I UAB MorphoPHEN Nephrons can be classifiied depending on: - The location: o superficial/cortical: have glomeruli located near the surface of the kidney and give rise to short-loop nephrons and do not penetrate into the inner medulla o Juxtamedullary: have glomeruli located deep within the cortex,near the cortico-medullary border, and give rise to long-loop nephrons and enter the inner medulla. - The lenght of the loop of Henle: o Long-segment nephron. o Short-segment nephron. Characteristic Superficial nephrons Juxtamedullary nephrons Outer layer of kidney Near junction of cortex and Location cortex medulla Loop of Henle Short Long length Reabsorb water and Create concentration Function electrolytes from filtrate gradient in medulla Tubule Part Location Type of Epithelium Histological Features Rounded nuclei, basal disposition, microvilli, Proximal Convoluted Tubules Renal Cortex Simple Cuboidal brush border, PAS-positive staining Distal Convoluted Tubules Renal Cortex Simple Cuboidal Cells without microvilli Varies in location, connecting proximal and Loops of Henle Renal Cortex and Medulla Flattened Cells distal tubules Simple Cuboidal to Collecting Ducts Renal Cortex and Medulla Drains distal tubules, leads to papillary ducts columnar epithelium Papillary Ducts Renal Medulla Transitional epithelium Drains from collecting ducts Endpoint within the Kidney Renal Pelvis (via Area Cribrosa) Transitional epithelium Drains urine from papillary ducts (Renal Pelvis) Every nephron has two components: the Malpiighian cropuscle and the tubular complex. Renal corpuscle or Malpighian copruscle. Glomerulus + Bowman’s capsule: The renal corpuscles are located exclusively in the renal cortex, and those located near the renal medulla are usually larger. 5 Module I UAB MorphoPHEN The glomerular capsule or Bowman’s capusle has two layers: External (parietal) layer: This layer is continuous with the proximal convoluted tubule. In male mice, it is a cuboidal epithelium, while in female mice, it is a squamous epithelium. In the mature male mouse it is lined by a cuboidal epithelium and its prevalence is influenced by age and circulating levels of testosterone. Male mouse glomerulus. The cuboidal parietal Female mouse glomerulus. The parietal epithelium resembles proximal convoluted tubule epithelium is thin (arrow); however, (PCT) epithelium (arrow). This change is variable occasionally in females low cuboidal depending on strain and increases with the age of epithelium may be present. Proximal tubule the mouse. Immature male glomeruli resemble (PC) and vascular pole (VP) are indicated. those of the femalemouse Internal (visceral) layer: This layer is formed by podocytes, which rest on the surface of the glomerular capillaries. Podocytes have cytoplasmic prolongations (pedicels) of two types: o First-order pedicels: These pedicels are much thicker. o Second-order pedicels: These pedicels contact the basement membrane of the glomerular capillaries, but they are not continuous with it, leaving spaces between them known as filtration slits. Bowman’s capsule has two poles: Vascular pole: important for the filtration of blood to form urine. The afferent arteriole brings blood into the glomerulus, where it is filtered under pressure. The filtrate then enters Bowman's space, and the remaining blood leaves through the efferent arteriole. Urinary pole: is the site where the proximal convoluted tubule arises. Important for the transport of the filtrate to the rest of the nephron, where it is further processed to form urine. 6 Module I UAB MorphoPHEN The glomerulus is the filtering unit of the kidney and consists of several capillary loops. The glomerulus is an assembly of four different cells: A. Glomerular Endothelial Cells Glomerular capillaries are not continuous. They are formed by large flat endothelial cells with large round fenestrations conected with each other by thin diaphragms. [Scanning electron micrograph illustrating the fenestrated glomerular endothelium] Underneath the endothelial cells is the glomerular basement membrane, and on the opposite side are located the glomerular epithelial cells (podocytes). B. Podocytes or glomerular emithelial cells (visceral layer of Bowman’s capsule) Specialized perivascular epithelial cells that cover the outer surface of the glomerular basement membrane, a thin layer that separates the glomerular capillaries from Bowman's space. Podocytes have long finger-like projections called pedicels, which wrap around the glomerular capillaries and form filtration slits. These slits are very narrow, but they allow water and small molecules to pass through into Bowman's space, while preventing larger molecules, such as proteins and blood cells, from passing through. C. Intraglomerular Mesangial Cells Contractile cells that are located in the center of the glomerulus, that support the glomerular capillaries and help to regulate blood flow through the glomerulus. Mesangial cells also produce a variety of proteins that are important for glomerular function. They help regulate blood flow through the glomerular capillaries and phagocytose debris. D. Parietal Epithelial Cells Line the outer layer of Bowman's capsule. These cells are continuous with the proximal convoluted tubule, the first part of the nephron. Parietal epithelial cells help to direct the flow of filtrate from Bowman's space into the proximal convoluted tubule. 7 Module I UAB MorphoPHEN Filtration barrier: 1. Fenestrated endothelium: glomerular endothelial cells. 2. Glomerular basement membrane. 3. Glomerular visceral epithelium: second-order pedicels of podocytes. Juxtaglomerular apparatus: The juxtaglomerular apparatus is located at the vascular pole of the glomerulus. It has 2 components: The vascular component: o Juxtaglomerular cells in the terminal portion of the afferent arteriole. It contains modified smooth muscle cells called Juxtaglomerular cells, which extend their processes into the initial portion of the efferent arteriole, where they release renin. o Extraglomerular mesangial region (vascual pole) containing Mesangium extraglomerular cells, that assist with communication between ascending and descending limbs of the loop of Henle. They also contain angiotensin-converting enzyme (ACE). The tubule component: macula densa is a group of modified epithelial cells in the distal convoluted tubule (DCT) of the kidneys (thick ascending limb). Lies adjacent to the afferent arteriole just before it enters the glomerulus (vascular component). When the macula densa senses a decrease in the concentration of sodium chloride in the filtrate, it signals to the juxtaglomerular cells to: A. Release renin in the initial portion of the efferent arteriole. Renin converts angiotensinogen, a protein that is produced in the liver, into angiotensin I. Angiotensin I is then converted into angiotensin II by angiotensin-converting enzyme (ACE), which is found in the lungs and other tissues (like mesangium extraglomerular cells). Angiotensin II is a powerful vasoconstrictor; when angiotensin II binds to angiotensin II receptors in the walls of blood vessels, it causes the vessels to constrict. This constriction increases blood pressure. B. Constrict the afferent arteriole (contraction of juxtaglomerular cells and intra- and extraglomerular mesangial cells). This constriction reduces blood flow to the glomerulus and decreases glomerular filtration rate (GFR, the rate at which blood is filtered by the glomerulus). 8 Module I UAB MorphoPHEN Tubular complex: Proximal tubule: the length of the proximal tubule is approximately 4 mm to 5 mm in the mouse. o Begins abruptly at the urinary pole of the glomerulus. o Proximal tubule cells have a well-developed brush border (red arrows). And the transition from the parietal epithelial cells of Bowman’s capsule to the proximal tubule cells is abrupt. [SEM image] o It consists of: ▪ An initial convoluted portion, the pars convoluta which is a direct continuation of the parietal epithelium of Bowman's capsule. ▪ A straight portion, the pars recta, which is located in the medullary ray. o Three morphologically distinct segments – S1, S2, and S3 – have been identified: ▪ S1 segment initial portion of the proximal tubule it begins at the glomerulus and constitutes approximately two thirds of the pars convoluta ▪ S2 segment consists of the remainder of the pars convoluta and the initial portion of the pars recta. ▪ S3 segment represents the remainder of the proximal tubule, located in the deep inner cortex and the outer stripe of the outer medulla. Most functional studies have distinguished between the convoluted and the straight portions of the proximal tubule rather than the S1 S2 and S3 segments. 9 Module I UAB MorphoPHEN Loop of Henle: o Thin descending limb of Henle: travels from the PT and forms a hairpin loop. ▪ It is highly permeable to water (which is easily transferred to the interstitium) and less permeable to solutes. o Thin ascending limb: after the thin descending limb (simple squamous epithelium), continues as the thick ascending limb (cuboidal epithelium without brush border) before terminating into the distal convoluted tubule. o The thin limbs (descending and ascending) are lined by simple squamous epithelium. Distal convoluted tubule: continues into the cortex from the ascending limb of the loop of Henle. Like the proximal convoluted tubule, it is called convoluted because it twists about. o The distal convoluted tubule is lined by a simple cuboidal epithelium without brush border. o The cells of the distal convoluted tubule (d) are smaller and more lightly stained than those of the proximal convoluted tubule (p). o More nuclei are apparent in a cross section of distal convoluted tubule compared to proximal convoluted tubule. 10 Module I UAB MorphoPHEN Collecting ducts: "collect" the urine fromdistal tubules. o Collecting ducts are lined by simple cuboidal epithelium which appears less specialized than that of the proximal or distal tubule. The cytoplasm is relatively clear (i.e., not as intensely eosinophilic) and cell borders are usually distinct. The epithelium gets more columnar when ducts are bigger. o They can be readily recognised in the renal medulla. o There is a gradual transition from the distal convoluted tubule to the cortical collecting duct, and the connecting tubule is not clearly demarcated because of intermingling of cells from neighbouring segments. ▪ There are two distinct cell types present in the collecting tubules: principal cells (the majority, less and smaller microvilli, respond to antidiuretic hormone (ADH) so are related with water reabsortion) and intercalated cells (more and bigger microvilli, regulate secretion of H+ and K+, and help to maintain the acid-base balance of the blood). Characteristic Principal cells Intercalated cells Proportion of Majority Minority cells in the collecting duct Main function Regulate water and Regulate acid-base sodium balance reabsorption Hormone Respond to ADH Do not respond to response ADH Water channels Express aquaporin- Do not express 2 channels aquaporin-2 channels Ion channels and Express channels Express channels transporters and transporters and transporters for sodium and for hydrogen ion water reabsorption and potassium secretion 11 Module I UAB MorphoPHEN Renal papilla: o Place where urine in the collecting ducts eventually empties into the renal pelvis (initial dilated portion of ureter characterized by a transitional epithelium, which allows it to stretch). o The mouse (!) papilla extends well into the renal pelvis. o The epithelium lining the outer surface of the renal papilla is an extension of the cuboidal epithelium of the distal collecting ducts, which under normal conditions, is a single-cell layer. Renal papilla (top) with single-cell layer lining epithelium contrasted to the multilayered true kidney pelvis urothelium (bottom) 2.2. Renal vascularization. Each kidney receives blood from a single renal artery, which is a direct branch of the abdominal aorta. Usually, before entering the hilus, the renal artery originates two branches, one cranial and one caudal, that immediately penetrate the renal parenchyma. Inside the renal sinus, the renal artery branches give rise the segmental arteries from which interlobar arteries originate and that form the limit of the renal pyramids. At the cortico-medullary border, interlobar arteries become arcuate arteries. Arcuate arteries give rise to the interlobular arteries, which are distributed throughout the renal cortex. o The afferent glomerular arterioles arise from the interlobular artery, that form the glomerulus capillary, and converge into efferent glomerular arterioles. Efferent arterioles finish in a capillary plexus. 12 Module I UAB MorphoPHEN The fate of the efferent arteriole depends upon the location of the glomerulus: ▪ Cortical nephron: forms the peritubular capillary networks around the proximal and distal convoluted tubules. ▪ Juxtamedullary nephron: forms the descending and ascending vasa recta around the loop of Henle. The hairpin configuration of the descending and ascending vasa recta allow for countercurrent exchange, which permits rapid osmotic equilibration between arterial and venous capillary blood. Descending vasa recta. As the vasa recta descends deeper into the medulla, the oxygen tension decreases and blood flow slows, such that the inner medulla is effectively anaerobic. Ascending vasa recta. The ascending vasa recta provide venous drainage for the medulla. It finally merges with venules draining the cortex to from the interlobular veins. Efferent arterioles finish in a capillary plexus that drains into the interlobular veins. In general, renal veins presented a path parallel to arteries and, consequently, they have the same names, they merge to form arcuate veins which give interlobar veins. Ultimately, they form the renal vein that exits the renal hilus and opens directly into the caudal vena cava. 2.3. Male sexual dimorphism of mouse kidney. Male sexual dimorphism of the mouse kidney includes larger organ size, cuboidal parietal epithelium, superficial cortical tubular vacuolation, and higher proteinuria. The features are variable, depending on strain and age. Female mouse cortex. Typical appearance of a 4- or 5-μm-thick section of cortex from either female mice or male mice with less vacuolation than noted in male mouse cortex. Male mouse cortex. Male mouse outer cortical tubular cells are variably vacuolated. This is an example of moderate vacuolation in an older male. 13 Module I UAB MorphoPHEN 3. Ureters. The ureter originates in the renal pelvis and leaves the kidney through the hilus, located at its medial border. The ureter follows a caudal path that is retroperitoneal in the abdominal portion. At the level of the pelvic cavity, the ureter opens into the urinary bladder. Before opening, the ureter runs intramurally between tunica muscularis and tunica mucosa of the urinary bladder. The ureteric orifice is the slit of the ureter at the lumen of the urinary bladder. 3.1. Histological structure: Mucosa: Transitional epithelium or Urothelium. o Three to eight layers thick and forms longitudinal folds that produce a stellate-shaped lumen on cross section. o The surface cells are characteristically dome-shaped and puffy. Lamina propia: containing elastic fibers and capillaries. Muscularis: thin inner and outer longitudinal layers and a prominent middle layer of smooth muscle; the thickness of the muscularis increases as the ureter approaches the bladder. Adventitia: composed of fibrous and adipose tissue, which in some areas is covered by mesothelium. 14 Module I UAB MorphoPHEN 4. Urinary bladder. The urinary bladder is located in the dorso-caudal area of the abdominopelvic cavity. When emptied of urine, the bladder is an ovoid structure with a maximum diameter of approximately 4 mm. (c) Ventral view of the abdominopelvic cavity. (d) The pubic symphysis region was dissected showing female urethra and urinary bladder. (e) Measurements of the urinary bladder (length: 8 mm) and female urethra (length: 11 mm) after alignment. a – e: EUO – external urethral ostium, PS – pubic symphysis, UB – urinary bladder and UR – female urethra. The urinary bladder is a hollow musculo- membranous organ whose size and shape varies depending on the amount of urine that it contains. In the urinary bladder it is possible to distinguish several parts: a vertex, which is located cranially; a body; and a neck that is continuous with the urethra. The median and lateral vesical ligaments attach the urinary bladder at the floor and lateral walls of the pelvic cavity, respectively. In the fetus, the median vesicle ligament contains the urachus whereas the lateral ligaments contain the umbilical arteries. Both structures collapse at birth. The collapsed umbilical arteries then form the round ligaments, located at the free edge of the lateral ligaments. 15 Module I UAB MorphoPHEN 4.1. Histological structure: Mucosa: a transitional epithelium, uniformly three cell layers deep is seen to line the entire bladder. Bladder capacity ranges from 0.15 ml in mice. o three types of cells are found: ▪ Cuboidal basal cells. ▪ Intermediate cells, which are the smallest of the three. ▪ Superficial cells, larger and can cover a number of intermediate cells. o The lamina propria is also highly vascularized. Muscularis: organized into three layers with a lot of connective tissue separating the muscle fiber bundles. The inner and outer layers are composed of longitudinal muscle fibers. Between them is found the intermediate layer that is formed by circular muscle fibers. Serosa: formed by the visceral peritoneum. When the bladder is empty the epithelium forms irregular folds that disappear on distension. 16 Module I UAB MorphoPHEN 5. Urethra. In females, the urethra is exclusive of the urinary apparatus, whereas in males it is also part of the reproductive system. Males: The urethra in male mouse is divided into membranous and penile. The membranous urethra extends from the bladder to the penis, where just prior to entrance it expands to a caudolateral bulbous diverticulum. Females: In female rodents, the urethra is shorter, but it has a similar anatomical structure as that of the male. It travels through the clitoris and empties at the clitoral fossa just ventral to the vaginal orifice. 17