THE MAMMALIAN URINARY BLADDERAN ACCOMMODATING ORGAN (1975)

Summary 1. Urinary bladders are found in the amphibia, chelonian reptiles and mammals. In these orders liquid urine is stored in the bladder and eliminated at intervals from the body by micturation. 2. In the amphibia and chelonian reptiles, the urinary bladder is a functional extension of the renal tubules. The composition of the urine in the bladder is modified by the active movement of water and ions across the bladder wall, and these transporting processes are under hormonal control. The bladder acts as a water reservoir which can be drawn upon in times of water shortage. 3. The mammalian bladder separates two widely differing water phases, namely the urine which is frequently hypertonic to the blood and the tissue fluids which are isotonic. Its function is uniquely one of storage, and no adjustment to the composition of the urine is made by active transport of either water or ions across the bladder wall. 4. The epithelium lining the mammalian bladder is the site of the osmotic barrier between urine and tissue fluids. This functional barrier is dependent on the structure of the epithelium and is maintained despite large alterations in the surface area of the epithelium as the bladder rapidly contracts, or slowly dilates. 5. The epithelium is of mixed mesodermal and endodermal origin, is transitional in type and is usually 3 or 4 cell‐layers thick. If this urothelium is damaged, it has a high capacity for regeneration and rapidly re‐establishes an intact barrier over the luminal surface. 6. The superficial cell layer of this epithelium is composed of large, polyploid, highly differentiated squamous cells which have a long life span. These cells are limited on their free surface by an unusual, angular, semi‐rigid luminal membrane. This membrane is assembled in the Golgi complex. 7. The luminal membrane is composed of thickened, discoidal plaques, separated by narrow bands of thinner membrane. When the bladder contracts, the membrane folds along the thinner ‘hinge’ regions, and the rigid discoidal plates invaginate to form fusiform, cytoplasmic vacuoles. The thickened plaques contain a hexagonal lattice of sub‐units, spaced at 14 nm centre‐to‐centre. Each sub‐unit in the lattice is itself composed of 12 smaller particles. These particles may be envisaged as small rods 3 nm in diameter and 12 nm long, and are inserted into matrix from which they project on the luminal face by about 3 nm. Each rod has a central hydrophobic portion separating distal hydrophilic ends. 8. The chemical composition of this luminal membrane is unusual. Cerebroside is a major component of the polar lipid fraction and there is an unusually high proline content in the protein fraction. When the mucoproteins are adequately dispersed, and the proteins separated by electrophoresis, a few major proteins are revealed in 33000–80000 dalton range of molecular weight. 9. If the normal structure of the luminal membrane is altered, either by physical damage or by failure of the cells to produce it, the barrier function of the epithelium is lost. 10. The structure and function of this membrane depend ultimately on its chemical composition. Cerebroside is known to decrease the permeability of lipid bi‐layers to water, but for maximum impermeability a lipid bi‐layer must be maintained in a condensed configuration. The stresses of bladder distension and contraction might be expected to disrupt the bi‐layer, and it is suggested that the function of the rigid plaque regions is to reduce mechanical stresses in the membrane to a minimum. The plaque areas occupy between 73 and 90 % of the membrane surface, and only the remaining 10–27% of the membrane is thus subject to bending and distortion when the bladder contracts or expands. The structure of the plaque areas is probably determined by the nature of the complex proteins which form the sub‐units. Proline is known to confer rigidity on polypeptide chains, and may play an important rôle in ordering the structure of the plaques. 11. The bladder epithelium, though normally differentiated as a transitional epithelium, has other biologicai potentialities. It can undergo squamous metaplasia to form a stratified cornified epithelium in response to mechanical irritation and/or vitamin A deficiency. If transplanted from its normal location, it can induce other supporting mesenchyme tissues to lay down bone. When regenerating in response to damage, the newly formed transitional cells can act as phagocytes and engulf and digest damaged or dying cells. In the normal animal the epithelium is largely protected from tumour formation by cell‐mediated immunological surveillance. The defensive mechanisms are triggered by tissue‐type specific antigens which develop in neoplastic bladder epithelial cells.