Urinary System Introduction to the Kidney - Gross appearance of the kidney varies considerably with species Unilobular kidney (carnivores) Multilobular kidney (swine, primates, ruminants) - Regardless of gross anatomic configuration, the histologic structure of all mammalian kidneys are the same The functions of the kidney are also universal Primarily a regulatory organ that controls extracellular fluid volume, electrolyte composition, and pH Also has an endocrine function, secreting various important substances o Renin – acid protease enzyme important in the control of blood pressure and volume o Erythropoietin – glycoprotein hormone that regulates RBC formation in response to decreased blood oxygen concentration o Hydroxylation of vitamin D3 (calcitrol) – a steroid precursor produced by the liver and regulated primarily by parathyroid hormone (PTH) Kidney Structure - Renal capsule The surface of the kidney is covered by a thick, CT capsule Consists of two distinct layers o Outer layer of dense fibroblasts (fibrocytes) and collagen fibers o Inner layer of myofibroblasts These contractile capsule cells may resist volume and pressure variations that accompany changes in renal function - Cortex and medulla The obvious division of the kidney shows the localized and specialized activities of the kidney o Outer cortex Highly vascular (dark red) area where filtration takes place Contains ~90-95% of blood passing through the kidney o Inner medulla Nearly avascular (white) area where urine concentration takes place Contains ~5-10% of the blood passing through the kidney - Nephron Structural and functional unit of the kidney The kidney exhibits ~1.5 million nephrons, though only ~10% are functional at any given time o This feature is a survival benefit because only a small number of nephrons are exposed to potentially-nephrotoxic agents at any one time Two types of nephrons exist and are named for the region of the kidney in which they are located o Medullary nephron 15% of nephrons Long-looped nephron that penetrates deeply into the medulla o Cortical nephron 85% of nephrons Short-looped nephrons whose limbs barely reach the medulla Nephron Structure: Renal Corpuscle - 200 microns in diameter (can be seen on a freshly-cut kidney surface) - Bowman’s capsule - Glomerulus Filtration apparatus of kidney Highly-specialized vascular structure consists of the glomerular basement membrane (GBM) o ~0.10 microns thick and resembles a thin ribbon Lamina densa and lamina rara are probably fixation artifacts o Composed mostly of type IV collage and laminin (contains much heparin sulfate) Laminin is a strong negatively-charged polyanion (charge barrier) that repels albumin (also negatively-charged) and keeps it out of glomerular filtrate o Lined by two important cell types Parietal endothelial cells line the inner surface - Single layer of squamous cells Podocytes cover the outer surface - Have primary processes that sprout secondary processes (pedicles), which encircle capillaries. Pedicles interdigitate with those from adjacent podocytes. The spaces between the pedicles (filtration slits) present a thin membrane (slit diaphragm) that consists of nephrin (a zipper-like protein) and has important control over what does and doesn’t enter glomerular filtrate Renal Corpuscle - - Glomerular mesangial cells Resident phagocytic cells of kidney Provide structural suppose Secrete IL-1 and PDGF Can differentiate to juxtaglomerular (JG) cells Juxtaglomerular (JG) apparatus Glomerulus Renal tubular system - The tubular portion of each nephron begins at the urinary pole of a renal corpuscle and ends at the junction of the tubule with a collecting duct - EM examination of renal tubular epithelium illustrates several different regions of the renal tubule Proximal convoluted tubules o Relatively long segment that dominates most sections taken from the cortex o Composed of proximal cells Demonstrates most selective resorption in the kidney Cuboidal-shaped, many mitochondria (high metabolic activity) Have microvilli (brush border) on luminal surface to increase absorption Canaliculi at base of microvilli enable protein resorption from glomerulus - Protein forms pinocytotic vesicle called “hyaline droplets” Tight junctions prevent leakage between adjacent cells Distal convoluted tubules o Cells lack microvilli and canaliculi o Cells have fewer mitochondria o Macula densa Where tubule rejoins glomerulus Integral part of JG apparatus o Tubules terminate at the collecting duct Proximal and Distal Tubules Thin segment o Consists of Loop of Henle Nephron tubule dips into medulla and returns to the cortex Thin descending limb Thin ascending limb Thick ascending limb - Removes Na+/Cl- from filtrate to allow water resorption & urine concentration - Water resorption requires high interstitial Na+ (1300 mOsmol) - Renal interstitium Consists of interstitial cell tissue (function unknown) between the tubules Prominent in the medulla, inconspicuous in the cortex Renal Circulation - Afferent and efferent arterioles enter and leave the renal corpuscle at the vascular pole - Efferent arteriole branches into a peritubular capillary network after leaving a glomerulus This network supplies the rest of the nephron Some efferent arterioles form a vasa recta o Efferent arteriolar loop within the renal medulla of a medullary nephron - After supplying the nephron, capillaries join venules, which join stellate veins, which empty into larger veins Stellate veins are easily seen on feline renal capsule (gives it a unique appearance) Lower Urinary Tract - Urothelium Transitional epithelium that lines lower urinary tract Has secretory activity that can modify urine composition Contains ions channels, receptors and ligands o Important for cell signaling o Allows for attachment and invasion of bacteria (uropathogenic E. coli) Histological appearance differs depending on whether bladder is relaxed or distended o Plaques (uroplakin) are formed in some regions due to thickened membrane In relaxed bladder, plaques invaginate into cell and appear as isolated vesicles (EM) In distended bladder, filaments attach to plaques to prevent over-stretching o Inter-plaque regions consist of non-thickened membrane - Ureter Narrow lumen when not distended (usual state) Mucosa has stellate appearance due to numerous longitudinal folds Mucosal wall lined by transitional epithelium, smooth muscle, and CT o Smooth muscle tissue (tunica muscularis) layers are organized in opposite fashion as GI tract Inner longitudinal Outer circular Vesicoureteral valve o Results from entry of ureter into bladder wall at oblique angle o Prevents bacterial transmission to ureter and renal pelvis o Prevents reflux of urine into ureters during bladder distension o Prevents higher hydrostatic pressure of urinary bladder from reaching renal pelvis - Urinary bladder Distensible reservoir for urine Trigone of the bladder is defined by the triangular region formed by 3 openings o Ureteric openings (2) o Internal urethral orifice (1) Mucosa o Composed of large, transitional epithelial cells called superficial cells Have extensive infoldings that interdigitate with membranes of transitional cells Desmosomes anchor transitional epithelial cells and maintain epithelial integrity o Basement membrane o Propria-submucosa Smooth muscle (tunica muscularis) o Detrusor m. (bladder wall) o Internal urethral sphincter m. (ring-like muscle around the internal urethral orifice) Innervated by both sympathetic and parasympathetic nerve fibers - Urethra Predominant lining is transitional epithelium o Variable patches of simple columnar or stratified cuboidal epithelium Mucosal surface is arranged into longitudinal folds that flatter or disappear during micturition Propria-submucosa consists of loose CT, smooth muscle and lymphoid (diffuse and nodular) tissue Male urethra is divided into three segments o Prostatic – extends from bladder to caudal edge of the prostate gland o Pelvic – extends from caudal edge of prostate to bulb of the penis o Penile – courses through the penis and terminates at the external urethra opening Female urethra is shorter than that of males o Vessels (endothelial-lined cavernous spaces) are scattered throughout CT of the propriasubmucosa layer giving the appearance of erectile tissue