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The urinary bladder is a storage vessel for most of the time, when intravesical pressure remains low and the outflow resistance high. During voiding a switch occurs when intravesical pressure rises and the outflow relaxes. The control of this change of function is regulated by a complex interplay between sensations arising from the lower urinary tract (LUT), coordination of responses in the brain and sacral spinal cord and control over bladder and the outflow tract. LUT function can become disorganized and commonly shows as overactive bladder (OAB) with symptoms of urgency and frequency, with or without incontinence. Several pharmaceutical approaches to manage OAB are possible which rely predominantly on manipulating mechanisms that generate detrusor contraction, initiate sensations of bladder filling or reduce the magnitude of outflow obstruction. The introduction of successful agents requires knowledge of the mechanisms that generate contraction in LUT tissues both in the normal and overactive bladder. The upper urinary tract propels urine from the kidney to the bladder by peristalsis, a process modulated by agents such as prostaglandins, produced by the ureters. Urinary tract stones collect in the upper tract and cause considerable morbidity. They are commonly formed of Ca oxalate/phosphate or magnesium ammonium phosphate. Various endogenous and artificial agents promote or inhibit stone formation and along with various mechanical procedures are used to manipulate the formation of upper tract stones.

The urinary bladder is a storage vessel for most of the time, when intravesical pressure remains low and the outflow resistance high. During voiding the reverse occurs when intravesical pressure rises and the outflow relaxes. The initiation and control of this change of function are carried out by a complex interplay between sensory mechanisms in the bladder, coordination of responses in the brain and sacral spinal cord and control over bladder and outflow muscle tone. Lower urinary tract (LUT) function can become disorganized and manifests commonly as overactive bladder (OAB) symptoms of urgency and frequency, with or without incontinence. The causes may be associated with neurogenic disorders, outflow tract obstruction or be idiopathic in the majority of cases. Several pharmaceutical approaches to manage OAB are possible which rely predominantly on manipulating mechanisms that generate detrusor contraction or reduce the magnitude of outflow obstruction. The introduction of successful agents requires knowledge of the mechanisms that generate contraction in LUT tissues both in the normal and overactive bladder. Several other potential approaches, such as reducing sensations from the urinary tract or modulating central nervous system pathways, are also briefly described.

An actionpotential is a transient depolarization of the membrane potential of excitable cells. They serve two main functions: to transmit and encode information, and to initiate cellular events such as muscular contraction. In this article actionpotentials generated in nerves will be the focus of attention. An actionpotential results from a transient change to the properties of the cell membrane, from a state where it is much more permeable to K+ than Na+, to a reversal of these permeability properties. Thus during the actionpotential an influx of Na+ is responsible for the rapid depolarization and an efflux of K+ causes repolarization. This ionic basis of the actionpotential can be predicted from the Nernst equation and is illustrated in the text. Changes to membrane ionic permeability are due to the opening and closing of voltage-gated ion channels, and the properties of such channels explain additional phenomena such as refractoriness, threshold and cellular excitability. Actionpotentials conduct with a finite velocity along nerve axons, and the actual velocity depends on a number of factors that include: fibre radius, temperature, functional ion channel number and the presence of a myelin sheath. The physical basis of conduction is explained by the local circuit hypothesis. Synaptic transmission of an actionpotential is explained in terms of excitatory post-synaptic potential (EPSP) generation at the post-synaptic membrane. The facility by which post-synaptic actionpotential may be developed is explained in terms of temporal and spatial summation as well as the influence of inhibitory transmitters.

Data from experiments or observations come in many forms and may be categorized as either qualitative or quantitative. One requirement of a data set is to summarize it by expressing two pieces of information: a single value that ‘summarizes’ the data set – a measure of central tendency – and a notion of the variability of the data set. Methods to express these two descriptors are described, exemplified by definitions of the mean and median, standard deviation and standard error of the mean, as well as concepts such as confidence intervals and coefficient of variation. An experiment often involves introducing an intervention, or assessing the effects of an intervention on a data set. Hypothesis testing is a concept that gives information about the statistical significance of such an intervention in changing the values of a data set. Planning an experiment is an integral part of the scientific method. Experiments may be either observational studies (prospective or retrospective) or interventional. In each case bias must be avoided either when choosing the particular samples and their number that make up the data set, or in analysing the data and methods to minimize confounding variables. Finally, the principles of evidence-based medicine are introduced.

Renal tract stones are common, more so in men, and among Asians and Caucasians, especially in warm climates. They are associated with a greater consumption of animal protein and refined foods, and decreased fluid intake. There are several types, most commonly consisting of calcium phosphates and oxalates; others are composed of magnesium ammonium phosphate (struvite), uric acid or cystine. Struvite stones are associated with urinary tract infections, often of urease-secreting bacteria that increase urinary ammonium concentration. Calcium stones may form for a number of reasons, including hypercalciuria and hyperoxaluria. Hypercalciuria may arise from changes to calcium resorption from bone, or renal and gastrointestinal tract handling of calcium; these are often associated with changes to parathyroid hormone secretion. Hyperoxaluria can arise from increased production or increased gut absorption. Other factors causing hypercalciuria include renal tubular acidosis or conditions that reduce the urinary concentrations of certain inhibitors, such as citrate and magnesium. Uric acid and cystine stones can form as a result of increased production or urinary concentration of the primary constituents. The assessment, investigation and management of patients with different types of stones is described.

The urinary tract conveys urine via the ureter to the bladder, where it is stored and periodically expelled. Dysfunction of the urinary tract ranges from bladder overactivity, due to outflow tract obstruction, neuropathic causes or an idiopathic condition, to renal colic often arising from the accumulation of stones. The management of such conditions with drugs and other regimens requires knowledge of the pharmacology of different tissues within the tract. This article examines how such knowledge has been used to regulate the sensory and contractile functions of the tract through currently used agents, and also considers potentially useful targets for future drug development. Particular targets include the urothelium, sensory and motor nerves, and smooth muscle of the bladder; the bladder outflow tract; the prostate; CNS components that regulate the micturition reflex; and the outflow tract. Evaluation of particular differences in the pharmacological control of each component increases the chance that useful therapeutic agents may be developed to target particular dysfunctions, while leaving normal function intact.

The bladder has two functions: to store urine and to periodically void the contents. The lower urinary tract has two components that must act in a coordinated way to achieve these functions: the urinary bladder and a competent sphincter mechanism. Urine storage is possible when the bladder is relaxed and compliant, and the sphincter offers a high resistance. Voiding occurs when the sphincter relaxes, and the bladder contracts to raise intravesical pressure. Urodynamics can illustrate these changes of function. Control of this coordinated system is mediated by a nervous pathway involving pontine centres that in turn exert control over a sacral reflex. The periaqueductal grey and pontine micturition centre play key roles in this central nervous control. Efferent control is achieved via autonomic and somatic pathways from the sacral spinal cord to the bladder and sphincter. Incontinence occurs when the system is deranged and may be due to bladder overactivity, sphincter dysfunction or bladder underactivity. There are many causes of these dysfunctions and drug management offers solutions in some cases.

This contribution discusses the problems facing the surgical trainee in obtaining a place on a PhD, MS or MD programme at a University in the UK.