Description
LUT: Anatomy
The bladder wall is formed by a mucosal and a muscular layer, surrounded by a serosa. The mucosa is lined by a stratifi ed epithelium, the urothelium, comprising three layers: a basal cell layer, an intermediate layer, and an apical layer of umbrella cells. The lamina propria contains several cell types including fi broblasts, mast cells, sensory nerve endings, and myofi broblasts (also referred to as interstitial cells; see below). It is also rich in afferent and efferent nerve endings, vascular and lymphatic vessels, collagen and elastic fi bers, and more or less well-defi ned smooth muscle fascicles [ 1 ].
The detrusor muscle is composed of three layers of smooth muscle. They are typical smooth muscle cells, without particular features that distinguish them from those found in other viscera. The cells of the outer and inner layers tend to be oriented longitudinally and those of the middle layer circularly. In the human detrusor, bundles of muscle cells of varying size are surrounded by connective tissue rich in collagen. Those muscular bundles vary extensively in size. In the human detrusor they are large, often a few millimeters in diameter, and composed of several smaller sub-bundles.
The Urothelium
The major (and classical) function of the urothelium is to act as a barrier to block the passage of substances excreted in the urine into the bladder wall. The urothelium is a transitional-type epithelium, containing three layers of cells: a basal cell layer, an intermediate layer, and a superfi cial layer containing hexagonal cells (umbrella cells). The latter have particular characteristics that concur to the barrier function of the urothelium. Among them, they have specialized membrane lipids, uroplakinrich asymmetric unit membranes, and a plasmalemma with stiff plaques. Uroplakins are transmembrane proteins that further reduce the permeability of the urothelium to small molecules like water, urea, and protons and can be used as a differentiation marker of umbrella cells. To reduce intercellular movement of molecules, occludinand claudin-rich tight junctions connect the lateral membrane of superfi cial cells. The luminal membrane of umbrella cells is covered by a glycosaminoglycan (GAG) layer that further reinforces the barrier function and seems to have antibacterial and anti-adherence properties. The origin of the GAG layer is still not clear, with at least part of it being synthetized by the kidneys to increase surface area. Fusiform or discoidal-shaped cytoplasmic vesicles docked in the apical cytoplasm fuse with the apical membrane, thereby increasing the luminal area. The presence of SNARE proteins essential for exocytosis was recently reported in urothelial cells and one of its isoforms (SNAP23) is extremely abundant in umbrella cells (Fig. 1.1 ).
While the urothelium has been historically viewed primarily as a barrier, it is becoming increasingly appreciated as a responsive structure capable of detecting physiological and chemical stimuli and able to release a signifi cant number of signaling molecules Thus, urothelial cells display a number of properties similar to sensory neurons and can use several signal-transduction mechanisms that perform an intricate cross talk with primary afferents located in the sub-urothelium. Urothelial cells express receptors for bradykinin, neurotrophins, as well as purinergic, cholinergic, adrenergic, and protease-activated receptors. Amiloride/ mechanosensitive Na + channels and several transient receptor potential channels are also found in the urothelium (Table 1.1 ). In addition, urothelial cells can release neurotransmitters and signaling molecules such as nitric oxide, ATP, acetylcholine, prostaglandins, substance P, and neurotrophins (Table 1.1 ) that infl uence the excitability of suburothelial afferent nerves. Mediators released by urothelial cells may eventually act indirectly on suburothelial myofi broblasts (also referred to as “interstitial cells”) that lie in close proximity to afferent nerves. Thus, it is believed that urothelial cells and myofi broblasts can participate in sensory mechanisms in the urinary tract in an autocrine/paracrine way.