Histology of Urinary System PDF
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Obafemi Awolowo University, Ile-Ife
Odukoya S. O. A. (Ph.D.)
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This document provides a detailed histology study of major tissues of the urinary system. It covers kidney structure, nephrons, renal tubules, and the urinary bladder. The document also includes information on the microscopic units of the kidney and related concepts.
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Histology of Major Tissues of Urinary System Odukoya S. O. A. (Ph.D.) Introduction: Capsule is made up of collagen fibers, some smooth muscle fibers and blood capillaries. The Parenchyma consists of millions of nephrons, branches of renal arteries, veins, lymphatics and...
Histology of Major Tissues of Urinary System Odukoya S. O. A. (Ph.D.) Introduction: Capsule is made up of collagen fibers, some smooth muscle fibers and blood capillaries. The Parenchyma consists of millions of nephrons, branches of renal arteries, veins, lymphatics and nerves. Introduction: Histology of the kidney Kidney is made up of billions of little tubes called the nephrons. At the beginning of each nephron, a web of capillaries releases much water and other molecules into the nephron. The urine is collected in the urinary bladder and, when it fills up, it is excreted via urethra into the outside environment. Kidney's Internal Structure Cortex -- the outer part of the kidney; Medulla -- the inner portion of the kidney; Pyramids -- the triangular- shaped divisions of the medulla of the kidney; Papilla -- narrow, innermost tip of the pyramid; Pelvis -- the kidney or renal pelvis is an extension of the upper end of the ureter (the tube that drains urine into the bladder); Calyx -- each calyx is a division of the renal pelvis; opening into each calyx is the papilla of a pyramid. The Nephron Nephron: basic structural and functional unit of the kidney. I ts chief function is to regulate the c o n c e n t ra t i o n o f w a t e r a n d s o l u b l e substances like sodium salts by f iltering the blood, reabsorbing what is needed and excreting the rest as urine. A nephron eliminates wastes from the body, regulates blood volume and blood pressure, controls levels of electrolytes and metabolites, and regulates blood pH. I ts f unc ti o ns are v i tal to l i f e and are regulated by the endocrine system by hormones such as antidiuretic hormone, aldosterone, and parathyroid hormone. Nephron structure: Characteristics Renal corpuscle: Capillary ball covered by podocyte & surrounded by simple squamous epithelial capsule, capsular space. Proximal convoluted tubule: Lined with simple cuboidal epithelium & prominent brush border Loop of Henle: Tubule that form a loop, there are thick & thin ascending & descending portion; the most distal part of the loop often extends into the medulla. Thick limbs are lined with simple squamous/cuboidal epithelium Thin limb are lined with simple squamous epithelium Distal convoluted tubule: Lined with simple cuboidal with only sparse brush border; cytoplasm of cells tend to be paler than that of proximal convoluted The Nephrons can be classified: On the basis of location of their glomeruli: Superficial (near the capsule) Mid cortical (near the medulla/Juxtamedullary) On the basis of the length of the loop of Henle: Short looped- generally have superficial or mid cortical glomeruli and the tubules extend only into the outer medulla before it reflects back into the cortex. Long looped- have juxtamedullary glomeruli and tubules extend into the inner medulla before The Nephron Microscopic units of a Kidney Have 2 main parts: 1. Renal corpuscle (Bowman's capsule with glomerulus) 2. Renal tubule. RENAL CORPUSCLE Glomerulus is surrounded by the Bowman's capsule. Bowman's capsule - the cup- shaped top of a nephron. It is the sack-like Bowman's capsule that surrounds the glomerulus. Glomerulus - a network of blood capillaries tucked into Bowman's capsule. Juxtaglomerular Apparatus The juxtaglomerular apparatus is a microscopic structure in the kidney, which regulates the function of each nephron. There are three cellular components of the apparatus which are the; Macula densa, Extraglomerular mesangial cells, Juxtaglomerular cells (a.k.a. granular cells). RENAL TUBULE Proximal convoluted tubule -- the f irst segment of a renal tubule, called proximal because it lies nearest the tubule's origin from Bowman's capsule, and convoluted because it has several bends in it. Loop of Henle -- the extension of the proximal tubule; observe that the loop of Henle consists of a straight descending (directed downward) limb, a loop, and a straight ascending limb (directed upwards). Distal convoluted tubule -- the part of the tubule distal to the ascending limb of Henle. It is the extension of the ascending limb of Henle. Collecting tubule -- a straight (not convoluted) part of a renal tubule; distal tubules of several nephrons join to form a single collecting tubule Histology of the Bowman's capsule Cells of the outer or parietal layer of Bowman's capsule form a simple squamous epithelium. Cells of the inner layer, podocytes in the visceral layer, are extremely complex in shape. Small foot-like processes, pedicles, of their cytoplasm form a fenestrated epithelium around the fenestrated capillaries of the glomerulus. The openings between the pedicles are called filtration slits. They are spanned by a thin membrane, the filtration slit membrane. Between the podocytes and the endothelial cells of the capillaries a comparatively thick basal lamina, which can be subdivided into an outer lamina externa, a middle lamina densa and an inner lamina interna. The basal lamina and the slit membranes form the glomerular filtration barrier, which prevents some large molecules from entering the capsular space between the outer and inner epithelial layers of Bowman's capsule. Histology of Histology of Histology of the the Proximal the Loop of Distal Tubule Henle Convoluted Tubule Walls - low It is 'U' shaped and Straight part of the DCT is columnar has descending and formed by the low epithelium. ascending cuboidal cells without a The eosinophilic segments. brush border. cells of the Thin descending The diameter of the epithelium have a segment has tubule gradually expands wide brush border flattened epithelium to about 35µ. and are active in (squamous). endocytosis. The convoluted part It is permeable to comes in contact with the water but not Glomerulus forming the solutes. Macula Densa. Ureter The wall of the ureter is made up of 3 layers. From inside outwards they are : Mucosa- thrown into folds and thus gives the appearance of star shaped lumen, made up of epithelium & lamina propria. 1. Transitional epithelium - 3-5 layers thickness. 2. Lamina propria - dense, irregular layer of fibroelastic connective tissue. The epithelium is separated from the lamina propria by a basal lamina. Muscular coat – made of smooth muscles. Upper 2/3 of the ureter is made of two layers of smooth muscle cells. Inner longitudinal and outer circular layer (in contrast to the wall of GIT which has inner circular & outer longitudinal!). Lower 1/3 of the ureter has a third outer layer of longitudinal muscles( inner longitudinal, middle circular, outer longitudinal). Fibrosa – made of fibrous connective tissue The urethra: Female: relatively short, exits just anterior to the vagina Male: longer, divided into three sections the prostatic, membranous and spongy urethra. The prostatic urethra is enclosed in the prostate gland. The membranous urethra is a short section that penetrates the urogenital diaphragm. The spongy urethra or penile urethra extends from the membranous urethra to the external urethral orifice (meatus). Histology: In both male and females the urethra starts out as transitional cell but quickly becomes stratified squamous in the female. The male urethra is more variable but ends up stratified squamous as well. Histology of the Urinary Bladder Introduction The urine formed by the nephrons of the kidneys is transported to the urinary bladder for storage before it gets expelled through the urethra. The urinary bladder is a sac that serves as a reservoir for urine. It is located in the extraperitoneal space of the pelvis behind the pubic bones and extends into the abdomen when filled with urine. The bladder divides into two main parts, each with its own features: the upper part, above the ureteric orifices, is composed of the apex and body, while the lower part is composed of the fundus, trigone, and neck. The capacity of the bladder is about 500 mL in healthy individuals. As the bladder fills, it stretches, simulating afferent signals. Efferent signals result in contraction of the bladder musculature and relaxation of the urethral sphincter, respectively. In addition to mechanoreceptors, various psychological factors like stress, sense of acceptable surroundings, and emotional status play a crucial role in the timing and setting of micturition. Structure The microscopic The microscopic structure of structure of the urinary the urinary bladder wall bladder wall organizes organizes into the following into the following layers layers from inside out: from inside out: Mucosa of transitional epithelium, Lining epithelium Submucosa, and Lamina propria Thick muscular layer (the Muscularis propria detrusor muscle) Serosa/Adventitia Serosa & Adventitia Lining epithelium: Urothelium The urinary bladder lining is a specialized stratified epithelium, the urothelium. The urothelium is exclusively in urinary structures such as the ureter, urinary bladder, and proximal urethra. In a relaxed urinary bladder, the urothelium is five to seven layers thick. When the urinary bladder fills with urine, the bladder wall stretches to accommodate the increased volume. In the distended bladder, the urothelium reorganizes into two or three layers without any structural damage. Due to this transitional ability of the urothelium, it is also known as the transitional epithelium. Lining epithelium: Urothelium The urothelium is composed of three layers: Apical layer - The innermost layer serves as a barrier between the bladder lumen and the underlying tissue. It is a single layer of umbrella-shaped cells (i.e., umbrella cells) that are frequently binucleated. These apical umbrella cells of the urothelium form an impermeable barrier; tight junctions between the cells decrease paracellular flux while a glycoprotein layer of uroplakin forms a superficial plaque that covers the umbrella cells. Intermediate layer - Formed from two to three layers of polygonal cells Basal layer - Formed from two to three layers of small cuboidal cells Lamina Propria: This is the sub-urothelial layer separating the urothelium and underlying muscularis propria (detrusor muscle). It is separated from the overlying urothelium by a basement membrane. Its composition is an extracellular matrix with elastic fibers, capillaries, lymphatics, immune cells, afferent and efferent nerve endings, fibroblasts, myofibroblasts, adipocytes, interstitial cells of Cajal or telocytes, an indistinct smooth muscle layer, and the muscularis mucosae. The interstitial cells of Cajal are within the lamina propria; they form a syncytium with the smooth muscle cells and nerve endings. The interstitial cells of Cajal are said to function as pacemaker cells in the gut, urethra, and prostate. In the bladder, they appear to act as nerve signal transducers to the bladder's smooth muscle cells. Muscularis propria: Also known as the detrusor muscle, It consists of three layers: inner longitudinal, middle circular, and outer longitudinal. These layers are well defined around the neck of the urinary bladder; however, in the rest of the bladder wall, they run randomly, without orientation. The bladder's body has a higher smooth muscle content compared with the trigone, reflecting a well- developed network of myofibroblasts of lamina propria and muscularis mucosae. Serosa and Adventitia: Serosa: This thin connective tissue layer covers the bladder dome and is continuous with the peritoneal layer of the abdominal wall. It also contains blood vessels of various sizes. Adventitia: This loose connective tissue layer serves as the bladder’s outer layer in areas of the bladder where there is no serosa. Function The urothelium transforms from five to seven cell layers thick in a relaxed state to two or three cell layers thick in a distended bladder. This functional modification of the epithelium does not cause any damage - resulting in the name "transitional epithelium" – and allows for the storage of urine. In its superficial layer, umbrella-shaped cells are connected by tight junctions and covered by uroplakin, thus making it a barrier preventing injury to the tissue below. The lamina propria, along with the urothelium, are sensory regions regulating the afferent limb of the micturition reflex. The lamina propria acts as a "functional center" of the bladder because of the presence of many specialized cells. It serves as a capacitance layer of the bladder that determines its compliance. The detrusor muscle of the muscularis propria is under autonomic nervous control. Sympathetic stimulation relaxes the detrusor muscle and contracts the urethral sphincter to allow the filling of urine, while parasympathetic stimulation contracts the detrusor and relaxes the urethral sphincter to allow micturition. Light Microscopy Under the light microscope, in a histological section of the bladder wall, the urothelium, lamina propria, muscularis propria, and serosa may be seen. The urothelium's most superficial layer is composed of dome-shaped umbrella cells whose shape becomes flat in a distended bladder. The cells of this layer are often multinucleated. Below the umbrella cells, the urothelium contains the multi-cell-layered intermediate and a single-cell layer of basal cells contacting its basement membrane. The cells of the intermediate layer are uni-nucleated; the number of layers in the intermediate layer depends on the stage of distension of the urinary bladder. The basal layer contains mononucleated, cuboidal cells with mitotic capability. Even though the rate of turnover is gradual, this layer demonstrates great regenerative capacity. The lamina propria is a sub-urothelial layer, the contents of which are described in the “Structure” section above. Electron Microscopy Umbrella cells demonstrate a characteristic ultrastructural feature; plaques or asymmetrical unit membrane. These are thick, focal areas of the cell membrane-associated with actin filaments. Actin filaments extend from the inner surface of the plaques to the cytoplasm of umbrella cells. In the non-distended bladder, the superficial cells appear to fold inwards; these folded plaques seemingly form membrane-bound, cytoplasmic fusiform vesicles. When the bladder distends during filling, these vesicles unfold to become part of a smooth surface as the cells flatten out. Clinical Correlates Clinicians use cystoscopy to examine the urinary bladder mucosa for pathology, which may be collected via biopsy sampling. Benign lesions include von Brunn’s nests. These islands or nests of the urothelium are separated from the luminal surface and consequently found within the lamina propria. Von Brunn’s nests of benign urothelium may undergo degeneration to form cysts (cystitis cystica). Conversely, malignant bladder tumors are graded based on their depth of invasion into the bladder wall. Childbirth and other events can injure the scaffolding that helps support the bladder in women. Pelvic floor muscles, the vagina, and ligaments support the bladder. Overactive bladder: Specifically, the symptoms of overactive bladder include urinary frequency—bothersome urination eight or more times a day or two or more times at night Urinary urgency: the sudden, strong need to urinate immediately Urge incontinence: leakage or gushing of urine that follows a sudden, strong urge to urinate Nocturia: awaking at night to urinate Pathophysiology Urge incontinence, a form of urinary incontinence, is characterized by urinary urgency. Etiologies include neurogenic, myogenic, or idiopathic causes. Disruption or damage of autonomic nerves, nerve signaling, or bladder cells may result in conditions including overactive bladder or bladder pain syndrome. Tissue Preparation Tissue biopsy for histopathological examination of the bladder is performed via cystoscopy or from radical cystectomy samples. Diagnosticians can use image-guided percutaneous bladder biopsy if there are contraindications to cystoscopy is contraindicated. Formalin-fixed tissue embedded in paraffin wax or frozen sections is useful for routine Histochemistry and Cytochemistry The umbrella-shaped top layer of cells is CK20+, and the basal cells are CD44+. In carcinoma in situ, all cells are CK20+, p53+, and show a greater Ki -67 proliferation index.