 \200 Occasional \200 \200 \200 Rare \200 More than one puncture site may be required. No guarantee of removal of all stones and need for further operations. Recurrence of stones. Severe kidney bleeding requiring transfusion, embolization, or, at last resort, surgical re moval of kidney. Damage to lung, bowel, spleen, liver, requiring surgical intervention. Kid ney damage or infection, needing further treatment. Over absorption of irrigating \202 ui ds into blood system, causing strain on heart function. \200 \200 Alternative treatment: external shock wave treatments, open surgical removal of stones, obs ervation. 1 Hopper KD, Sherman JL, Williams MD, et al. (1987) The variable anteroposterior position o f the retroperitoneal colon to the kidneys. Invest Radiol 22:298 \200\223302. 2 J Endourol 2:59 \200\22362. Inglis JA, Tolly DA (1988) Antibiotic prophylaxis at the time of percutaneous stone surgery . 3 Martin X (2000) Severe bleeding after nephrolithotomy: results of hyperselective embolisa tion. Eur Urol 37:136 \200\2239. 4 Clayman J (1987) Percutaneous nephrostomy: Assessment of renal damage associated with sem i-rigid (24F) and balloon (36F) dilation. J Urol 138:203 \200\2236. This page intentionally left blank CHAPTER 17 Urological surgery and equipment 778 Ureteroscopes and ureteroscopy The instruments Two types of ureteroscope in common use \200 \224the semi-rigid ureteroscope and the \202 exible ureteroscope. Semi-rigid ureteroscopes Have high-density \201 bre optic bundles for light ( \200\230non -coherently \200\231 arranged) and image transmission ( \200\230coherently \200\231 arrange d to maintain image quality). For equivalent light and image transmission using glass rod l enses, thicker lenses are required than with \201 bre optic bundles. As a consequence, se mi- rigid ureteroscopes can be made smaller while maintaining the size of the instrument ch annel. In addition, the instrument can be bent by several degrees without the image being d istorted. The working tip of most current models is in the order of 7 \200\2238 Ch, with the proximal end of the scope being in the order of 11 \200\22312 Ch. There is usually at least one wor king channel of at least 3.4 Ch. Flexible ureteroscopes The \201 bre optic bundles in \202 exible ureteroscopes are the same as those in semi-rigid scopes, only of smaller diameter. Thus, image quality and light transmission are not as good as with semi-rigid scopes, but are usually adequate. The working tip of most current models is in the order of 7 \200\2238 Ch, with the proximal end of the scope being in the order of 9 \200\22310 Ch. There is usually at least one work ing channel of at least 3.6 Ch. The great advantage of the \202 exible ureteroscope over the semi-rigid variety is the ab ility to perform controlled de \202 ection of the end of the scope (active de \202 ection ). Behind the actively de \202 ecting tip of the scope is a segment of the scope which is more \202 exible than the rest of the shaft. This section is able to undergo passive de \202 ection \200\224when the tip is fully actively de \202 ected by advancing the scope fu rther, this \202 exible segment allows even more de \202 ection. Flexible ureteroscopes have recently been developed which have two actively de \202 ecting segments. Flexible ureteroscopes are intrinsically more intricate and are, there- fore, less durable than semi-rigid scopes. Ureteroscopic irrigation systems Normal saline is used (high-pressure irrigation with glyci ne or water would lead to \202 uid absorption from pyelolymphatic or venous back \202 ow ). Irrigation by gravity pressurization alone (the \202 uid bag suspended above the patie nt without any applied pressure) will produce \202 ow that is inad- equate for visualizat ion because the long, \201 ne bore irrigation channels of modern ureteroscopes are inhere ntly high resistance. Several methods are available \200\224hand-in \202 ated pressure bag s, foot pumps, and hand-operated syringe pumps. Whatever system is chosen, use the minimal \202 ow required to allow a safe view so as to avoid \202 ushing the stone out of the u reter and into the kidney, from where you may not be able to retrieve it. URETEROSCOPES AND URETEROSCOPY 779 Ureteric dilatation Some surgeons do, others don \200\231t. Those who don \200\231t argue t hat dilatation is unnecessary in the era of modern, small-caliber ureteroscopes. Those who do cite a higher chance of being able to pass the ureteroscope all the way up to the kidney . Ureteric dilatation may be helpful where mul- tiple passes of the ureteroscope up and dow n the ureter are going to be required for stone removal (alternatively, use a ureteric acce ss sheath). Some surgeons prefer to place two guidewires into the ureter, one to pass the u reteroscope over ( \200\230railroading \200\231) and the other to act as a safety wire so t hat access to the kidney is always possible if dif \201 culties are encoun- tered. The sec ond guidewire is most easily placed via a dual lumen cath- eter which has a second channel through which the second guidewire can be easily passed into the ureter without requiring r epeat cystoscopy. This dual lumen catheter has the added function of gently dilating the ur eteric ori \201 ce to about 10 Ch. There is probably no long-term harm done to the ureter as a consequence of dilatation.1 Ureteric access sheaths, which have outer diameters from 10 to 14 Ch, may facilitate access to the ureter and are particularly useful if it is antici- pated that the ureteroscope wil l have to be passed up and down the ure- ter on multiple occasions (to retrieve fragments o f stone). In addition, they facilitate the out \202 ow of irrigant \202 uid from the pel vis or the kidney, thereby maintaining the \201 eld of view and decreasing intrarenal pre ssures. Patient position The patient is positioned as \202 at as possible on the operating table to \200\230iron out \200\231 the natural curves of the ureter. A cystoscopy is performed w ith either a \202 exible or rigid instrument. A retrograde ureterogram can be done to out line pelvicalyceal anatomy. A guidewire is then passed into the renal pelvis. We use a Sens or guidewire (Microvasive, Boston Scienti \201 c) which has a 3cm long \202 oppy, hydrop hilic tip which can usually easily be negotiated up the ureter. The remaining length of the wire is rigid and cov- ered in a smooth PTFE. Both properties aid passage of the ureterosc ope. Technique of \202 exible ureteroscopy and laser treatment for intrarenal stones Flexible ureteroscopy and laser treatment can be performed with topical urethral local anesthesia an d sedation. However, trying to fragment a mov- ing stone with the laser can be dif \201 cu lt and ideally, therefore, ureteroscopy is most easily done under general anesthesia with e ndotracheal intubation (rather than a laryngeal mask) to allow short periods of suspension of respi- ration and so stop movement of the kidney and its contained stone. Empty the bladder to prevent \200\230coiling \200\231 of the scope in the bladder. Pass th e scope over a guidewire. This requires two people \200\224the surgeon holds the shaft of t he scope and the assistant applies tension to the guidewire to \201 x the latter in posit ion without pulling it down. This allows the scope to progress easily up the ureter. The as sistant also ensures that acute angulation of the scope where the handle meets the shaft do es not occur. The \202 exible ureteroscope should slide easily up the ureter and into the renal pelvis. With modern active secondary de \202 ection ureteroscopes, access to most, if not all, parts of the renal collecting system is possible. CHAPTER 17 Urological surgery and equipment 780 Laser lithotripsy The main drawback of laser lithotripsy is the dust-cloud effect that occu rs as the stone is fragmented. This temporarily obscures the view and must be washed away b efore the laser can safely be re-applied. The use of stone baskets to retrieve stones after ureteroscopy The aim of ureteroscopy (or \202 exible ureterorenoscopy) is to remove the ure- teric (or renal) stone. It, therefore , seems intuitive to remove any large frag- ments \200\224leaving them in situ runs the ris k of ureteric colic post-ureteroscopy. To stent or not to stent after ureteroscopy JJ stent insertion does not increase stone-free rates and is, therefore, not required in \200\230routine \200\231 cases. A stent should b e placed if: \200 There has been ureteric injury (e.g. perforation \200\224indicated by extravasation of cont rast). There are residual stones that might obstruct the ureter. The patient has had a uret eric stricture that required dilatation. Solitary kidneys. \200 \200 Routine stenting after ureteroscopy for distal ureteric calculi is unneces- s ary.2 Many urologists will place a stent after ureteroscopy for proximal ureteric stones. Complications of ureteroscopy Septicaemia; ureteric perforation, requiring either a JJ sten t or, very occa- sionally, a nephrostomy tube where JJ stent placement is not possible; ure teric stricture (<1%). BAUS procedure-speci \201 c consent form: recommended discussion of adverse events Serious or frequently occurring complications of ureteroscopy for treatment of ureteric stones Com mon \200 Mild burning or bleeding on passing urine for a short period after the operation. Temporary insertion of a bladder catheter may be required. Insertion of a stent may be required with a further procedure to remove it. Urinary infections, occasionally requiring antibiotics. \200 Occasional \200 Inability to get stone or movement of stone back into kidney where it is not retrievable. K idney damage or infection, requiring further treatment. Failure to pass scope if ureter is narrow. Recurrence of stones. \200 \200 URETEROSCOPES AND URETEROSCOPY 781 Rare \200 Damage to ureter with need for open operation or placement of a nephrostomy tube into the k idney. Alternative treatment: open surgery, shock wave therapy, or observation to allow spontaneou s passage. 1 Garvin TJ, Clayman RV (1991) Balloon dilation of the ureter for ureteroscopy. J Urol 146: 742 \200\2235. 2 Srivastava A, Gupta R, Kumar A, Kapoor R, Mandhani A (2003) Routine stenting after ureter os- copy for distal ureteral calculi is unnecessary: results of a randomized controlled tri al. J Endourol 17:871. CHAPTER 17 Urological surgery and equipment 782 Pyeloplasty Indications: PUJ obstruction. Anesthesia: general. Post-operative care A JJ stent, bladder catheter, and a drain are left in situ. The bladder catheter serves to prevent re \202 ux of urine up the ureter, which can lead to increased leakage of urine from the anastomosis site (re \202 ux occurs because of the presence of the JJ stent). The drain is removed when the drain output is minimal. The stent is left in position for about 6 weeks. Common post-operative complications and their management Hemorrhage Usually arising from th e nephrostomy track (if a nephrostomy tube has been left in place \200\224some surgeons lea ve a JJ stent and a perinephric drain, with no nephrostomy). Clamp the nephrostomy tube in an attempt to tamponade the bleeding. If the bleeding continues, consider angiography and e mbolization of the bleeding vessel if seen or exploration. Urinary leak This can occur within the \201 rst day or so. If a urethral catheter has not been left in place, catheterize the patient to minimize bladder pressure and, therefore, t he chance of re \202 ux which might be responsible for the leak. If the drainage persists for more than a few days, shorten the drain \200\224if it is in contact with the suture lin e of the anastomosis, it can keep the anas- tomosis open, rather than letting it heal. If t he leak continues, identify the site of the leak by either a nephrostogram (if a nephrostom y has been left in situ) or a cystogram (if a JJ stent is in place \200\224contrast may re \202 ux up the ureter and identify the site of leakage) or an IVU. Some form of additional drainage may help \200\230dry up \200\231 the leak (a JJ stent if only a nephrostomy has been left in situ or a nephrostomy if one is not already in place). Obstruction at PUJ This is uncommon and if it occurs, it is usually detected once all the t ubes have been removed and a follow-up renogram has been done. If the patient had symptomat ic PUJO, but remains asymptomatic, then no further treatment may be necessary. If they deve lop recurrent \202 ank pain, re-operation may be necessary. Acute pyelonephritis Manage with antibiotics. PYELOPLASTY 783 BAUS procedure-speci \201 c consent form: recommended discussion of adverse events Serious or frequently occurring complications of pyeloplasty Common \200 \200 Temporary insertion of a bladder catheter and wound drain. Further procedure to remove uret eric stent, usually a local anesthetic. Occasional \200 Rare \200 \200 Very rarely \200 \200 Bleeding, requiring further surgery or transfusion. Recurrent kidney or bladder infections. Recurrence can occur, needing further surgery. Entry into lung cavity, requiring insertion of temporary drainage tube. Anesthetic or cardi ovascular problems, possibly requiring intensive care admission (including chest infection, PE, stroke, DVT, heart attack). Need to remove kidney at a later time because of damage ca used by recurrent obstruction. Infection, pain, or hernia of incision, requiring further tr eatment. Alternative therapy: observation, telescopic incision, dilation of area of narrowing, tempo rary placement of plastic tube through narrowing, lapar- oscopic repair. CHAPTER 17 Urological surgery and equipment 784 Laparoscopic surgery Virtually every urological procedure can be done laparoscopically. It is particularly suited to surgery in the retroperitoneum (nephrectomy for benign and malign ant disease and for kidney donation at transplantation, pyeloplasty for PUJO), but it is al so suited to pelvic surgery (lymph node biopsy, radical prostatectomy). Reconstructive surg ery requiring laparo- scopic suturing and using bowel is technically very challenging, but pos- sible. Laparoscopic surgery offers the advantage over open surgery of: \200 \200 \200 \200 Reduced post-operative pain. Smaller scars. Less disturbance of bowel function (less post-o perative ileus). Reduced recovery time and reduced hospital stay. Contraindications to laparoscopic surgery \200 Severe COPD (avoid use of CO2 for insuf \202 ation). \200 Uncorrectable coagulopathy. \200 Intestinal obstruction. \200 Abdom inal wall infection. \200 Massive haemoperitoneum. \200 Generalized peritonitis. \200 Suspected malignant ascites. Laparoscopic surgery is dif \201 cult or potentially hazardous in the mor- bidly obese (in adequate instrument length, decrease range of movement of instruments, higher pneumoperiton eum pressure required to lift the heavier anterior abdominal wall, excess intra-abdominal f at limiting the view); those with extensive previous abdominal or pelvic surgery (adhe- sio ns); previous peritonitis, leading to adhesion formation; in those with organomegaly; in th e presence of ascites; in pregnancy; in patients with a diaphragmatic hernia; in those with aneurysms. Potential complications unique to laparoscopic surgery Gas embolism (potentially fatal), hy percarbia (acidosis affecting cardiac function, e.g. arrhythmias), post-operative abdominal crepitus (subcutane- ous emphysema), pneumothorax, pneumomediastinum, pneumopericar- dium, barotraumas. Bowel, vessel (aorta, common iliac vessels, IVC, anterior abdominal wall injury), and other viscus injury are not unique to laparoscopic surgery, but are a particular concern during port access. Perforation of small or large bowel is the most common trocar injury. Rarely, the bladder is perforated. Failure to progress with a laparoscopic approach or vessel injur y with uncontrollable hemorrhage requires conversion to an open approach. Post-operatively, bowel may become entrapped in the trocar sites or there may be bleeding from the sheath si te. An acute hydrocele can develop due to irrigation \202 uid accumulating in the scrotum . It resorbs spontaneously. Scrotal and abdominal wall bruising not uncommonly occurs. LAPAROSCOPIC SURGERY 785 BAUS procedure-speci \201 c consent forms For all laparoscopic procedures Common \200 \200 \200 Occasional \200 Rare \200 \200 Very rarely \200 Temporary shoulder tip pain. Temporary abdominal bloating. Temporary insertion of a bladder catheter and wound drain. Infection, pain, or hernia of incision, requiring further treatment. Bleeding, requiring conversion to open surgery or transfusion. Entry into lung cavity, requ iring insertion of a temporary drainage tube. Recognized (and unrecognized) injury to organs or blood vessels, requiring conversion to op en surgery or deferred open surgery. Anesthetic or cardiovascular problems, possibly requir ing intensive care admission (including chest infection, PE, stroke, DVT, heart attack). Laparoscopic pyeloplasty Common \200 Further procedure to remove ureteric stent, usually under local anesthesia. Occasional \200 \200 Recurrence can occur, needing further surgery. Short-term success rates are similar to open surgery, but long-term results unknown. Very rarely \200 Need to remove kidney at a later time because of damage caused by recurrent obstruction. Alternative therapy: observation, telescopic incision, dilation of area of narrowing, tempo rary placement of a plastic tube through narrowing, con- ventional open surgical approach. Laparoscopic simple nephrectomy Occasional \200 Short-term success rates are similar to open surgery, but long-term results unknown. Alternative therapy: observation and conventional open surgical approach. Laparoscopic radical nephrectomy Occasional \200 Short-term success rates are similar to open surgery, but long-term results unknown. Rare \200 A histological abnormality other than cancer may be found. Alternative therapy: observation, embolization, chemotherapy, immuno- therapy, conventional open surgical approach. CHAPTER 17 Urological surgery and equipment 786 Endoscopic cystolitholapaxy and (open) cystolithotomy Indications \200 Endoscopic cystolitholapaxy: The de \201 nition of \200\230small \200\231 is debatable. M any stones <4cm in diameter can be removed endoscopically, but the greater the number and s ize of the stones, the more inclined will the surgeon be to adopt an open approach. Having said this, if you anticipate that the patient is likely to develop recurrent stones and, th erefore, will require multiple future procedures to remove them, then try to avoid open sur gery because each redo open cystolithotomy will be more dif \201 cult (due to the presence of scar tissue). Open cystolithotomy: stones (though some surgeons will be happy to \200 \230take on \200\231 larger stones endoscopically); patients with urethral obstruction whic h precludes endoscopic access to bladder. generally indicated for small stones. for stones >4cm in diameter and/or multiple Anesthesia: regional or general. Post-operative care A catheter is left in the bladder for a day or so since haematuria is c om- mon, particularly after fragmentation of large stones. Irrigation may be required if th e haematuria is heavy. Common post-operative complications and their management Haematuria requiring bladder washo ut or return to theater is rare. Septicaemia: uncommon. Bladder perforation: uncommon, but can occur with the use of stone \200\230punches \200 \231 which grab the stone between powerful cutting jaws. Grasping the bladder wall in the j aws of the stone forceps or punch is easily done and can cause perforation. BAUS procedure-speci \201 c consent form: recommended discussion of adverse events Serious or frequently occurring complications of endoscopic cystolitholapxy Common \200 Mild burning or bleeding on passing urine for short periods after operation. Temporary inse rtion of a catheter. Occasional \200 \200 \200 Rare \200 Infection of bladder requiring antibiotics. Permission for removal/biopsy of bladder abnorm ality, if found. Recurrence of stones or residual stone fragments. Delayed bleeding, requiring removal of clots or further surgery. ENDOSCOPIC CYSTOLITHOLAPAXY, (OPEN) CYSTOLITHOTOMY 787 Very rarely \200 Injury to urethra, causing delayed scar formation. Perforation of bladder, requiring a temporary urinary catheter or return to theater for ope n surgical repair. Alternative therapy: open surgery, observation. CHAPTER 17 Urological surgery and equipment 788 Scrotal exploration for torsion and orchidopexy Indications: suspected testicular torsion. Technique A midline incision since this allows access to both sides so that they may both b e \200\230 \201 xed \200\231 within the scrotum. Untwist the testis and place in a warm, saline-soaked swab for 10min. If it remains black, remove it, having ligated the spermatic cord with a trans \201 xion stitch of absorbable material. If it \200\230pinks up \200 \231, \201 x it. If uncertain about its viability, make a small cut with the tip of a sca lpel. If the testis bleeds actively, it should be salvaged (close the small wound with an a bsorbable suture). If not, it is dead and should be removed. Whatever you do, \201 x the other side. Fixation technique Some surgeons \201 x the testis within the scrotum with suture materia l, inserted at three points (3-point \201 xation). Some use absorbable sutures and others non-absorbable. Those who use the latter argue that absorb- able sutures may disappear, ex posing the patient to the risk of retorsion.1 Those who use absorbable sutures argue that t he \201 brous reaction around the absorbable sutures prevents retorsion and argue that th e patient may be able to feel non-absorbable sutures which can be uncomfortable. The suture s should pass through the tunica albuginea of the testis and then through the parietal laye r of the tunica vaginalis lining the inner surface of the scrotum. Others say the testis should be \201 xed within a dartos pouch,2 arguing that suture \201 xation breaches the blood \200\223testis barrier, exposing both testes to the risk of sympathetic orchidopathia (an autoimmune reac- tion caused by development of antibodies aga inst the testis). For dartos pouch \201 xation, open the tunica vaginalis, bring the test is out, and untwist it. Develop a dartos pouch in the scrotum by holding the skin with forc eps and dissecting with scissors between the skin and the underlying dartos muscle. Enlarge this space by inserting your two index \201 ngers and pulling them apart. Place the test is in this pouch. Use a few absorbable sutures to attach the cord near the testis to the in side of the dartos pouch to prevent retorsion of the testes. The dartos may then be closed over the testis and the skin can be closed in a separate layer. Post-operative care and potential complications and their management As for all procedures involving scrotal exploration, a scrotal haematoma may result, which may have to be surgica lly drained. SCROTAL EXPLORATION FOR TORSION AND ORCHIDOPEXY 789 BAUS procedure-speci \201 c consent form: recommended discussion of adverse events Serious or frequently occurring complications of scrotal exploration Common \200 Occasional \200 \200 The testis may have to be removed if non-viable. You may be able to feel the stitch used to \201 x the testis. Blood collection around the testes which slowly resolves or requires surgical removal. Possible infection of incision or testis, requiring further treatment. Rare \200 \200 Loss of testicular size or atrophy in future if testis is saved. No guarantee of fertility. Alternative therapy: observation \200\224risks loss of testis and autoimmune reaction, lead ing to subfertility and loss of hormone production in remain- ing testis. 1 Kuntze JR (1985) Testicular torsion after orchidopexy. J Urol 134:1209 \200\22310. 2 Frank JD (2002) Fixation of the testis. Br J Urol Int 89:331 \200\2233. CHAPTER 17 Urological surgery and equipment 790 Electromotive drug administration (EMDA) EMDA is a non-invasive method of enhancing drug pe netration across the bladder urothelium (and prostatic urethra), resulting in greater quant ities of local drug being delivered to a greater tissue depth than is achievable by passive diffusion alone. It avoids many of the side effects seen with systemic administration. Mechanism of action EMDA uses an electric current to accelerate and actively transportation ionized molecules into tissues. Drug administration can, therefore, be control- led by alt ering the electric current intensity. The two main electrokinetic principles are: iontophor esis (transportation of ionized molecules into tissue by applying a current across a soluti on containing the ions, e.g. lidocaine) and electro-osmosis (transportation of non-ionized solutes associated with the bulk transportation of water, e.g. mitomycin C). Applications in urology \200 Local anesthesia (LA) of the bladder (and prostatic urethra) prior to other procedures: \202 exible and rigid cystoscopy with biopsy and cystodiathermy, TURBT, BNI, TUIP, intraves ical capsaicin therapy, and botulinum toxin-A injections. Intravesical mitomycin C therapy for TCC of the bladder. Intravesical oxybutynin therapy for OAB. Antibiotic administration (i.e. gentamicin) for infective recalcitrant cystitis. LA with anti-in \202 ammatory drugs for cystodistention. \200 \200 \200 Method of EMDA LA It can be performed as a day case or outpatient procedure. A CE-DAS URO GENICS catheter electrode* (Fig. 17.16) is inserted urethrally and the bladder emptied an d irrigated with sterile water to remove any residual urine. A total of 150mL of 0.5% bupiv acaine and 1.5mL (1.5mg) of 1/1000 epinephrine is instilled into the bladder. Two dispersiv e electrode pads are placed on the lower abdomen and both the electrode pads and the cathet er are connected to the PHYSIONISER generator* set to positive polarity, 25mA current str ength, a pulsed current with rise rate 50 A/s for 23min. The catheter is then removed and endoscopy can proceed. EMDA LA is effective for 60min. Contraindications to EMDA LA Allergy to LA, signi \201 cant haematuria, patients on monoam ine oxidase inhibitors. Relative contraindications Active infection of lower genitourinary tract, protrusion of enl arged median lobe of prostate into the bladder, urethral stricture, bladder neck stenosis. Physion Srl, Medolla, Italy. ELECTROMOTIVE DRUG ADMINISTRATION (EMDA) 791 Fig. 17.16 EMDA in bladder and prostate using catheter electrode (Reproduced with permissio n from Physion S.r.l.) This page intentionally left blank 793 Chapter 18 Basic science and renal transplant Basic physiology of bladder and urethra 794 Basic renal anatomy 796 Renal physiology: glome rular \201 ltration and regulation of renal blood \202 ow 800 Renal physiology: regulation of water balance 802 Renal physiology: regulation of sodium an d potassium excretion 803 Renal physiology: acid \200\223base balance 804 Renal replacement therapy 806 Renal transpl ant: recipient 808 Renal transplant: donor 810 Transplant surgery and complications 812 CHAPTER 18 Basic science and renal transplant 794 Basic physiology of bladder and urethra Bladder The bladder has an endothelial lining (urot helium) on a connective tis- sue base (lamina propria), surrounded by smooth muscle (detrus or), with outer connective tissue (adventitia). Urothelium consists of multi- layered trans itional epithelium, with numerous tight junctions that render it impermeable to water and s olutes. Detrusor muscle is a homogeneous mass of smooth muscle bundles. C-kit antigen-posit ive \200\230interstitial cells \200\231 exist around detrusor bundles and in the suburothe lium and play a role in modulating contractile behavior of adjacent smooth muscle. The blad - der base is known as the trigone \200\224a triangular area with the two ureteric ori \201 ces and the internal urinary meatus forming the corners. Intravesical pressure during \201 lling is low. The main excitatory motor input to the blad- der is from the autonomic nervous system and is predominantly parasym- pathetic innervation (S2 \200\2234). Pregangl ionic nerve \201 bres are conveyed to the bladder in the pelvic nerves and then synapse w ith cholinergic post- ganglionic nerve cells in the pelvic plexus and on the bladder, which , when activated, cause muscle contraction. Sympathetic innervation (T10 \200\223L2) plays a role in urine storage (see b p. 592). Urethra The bladder neck (and posterior urethra) is normally closed during \201 lling. It is composed of circular smooth muscle (with sympathetic innervation) and is also referred to as the internal sphincter. High pressure is generated at the midpoint of the urethra in women and at the level of the membra- nous urethra in men where the urethral wall is compos ed of a longitudinal and circular smooth muscle coat, surrounded by striated muscle (extern al urethral sphincter). The striated part of the sphincter receives motor innervation from the somatic pudendal ner ve derived from (S2 \200\2234) in a region in the sacral spinal cord called \200\230Onuf \200\231s nucleus \200\231. It has voluntary control and acetyl- choline (ACh) mediates con traction. The smooth muscle component of the sphincter has myogenic tone and receives excit atory and inhibitory innervation from the autonomic nervous system. Contraction is enhanced by sympathetic input (noradrenaline) and Ach. Inhibitory innervation is nitrergic (nitric oxide; see b pp. 593 \200\2234). Micturition As the bladder \201 lls, sensory afferent nerves respond to stretch in the bl ad- der wall and send information about bladder \201 lling to the central nervous system (CNS). During urine storage, the pontine storage center medi- ates enhanced external urethr al sphincter activity (so causing constric- tion of the sphincter). There is also somatic o ut \202 ow via the pudendal nerve to the external striated sphincter muscle to cause contr action and sympathetic out \202 ow to constrict the internal smooth muscle sphincter (blad der neck) and also inhibit ganglia in the bladder wall. At a socially acceptable time, the voiding re \202 ex is activated (Fig. 18.1). Neurones in BASIC PHYSIOLOGY OF BLADDER AND URETHRA 795 the periaqueductal gray (PAG) matter in the pons trigger a switch to the pontine micturitio n center (PMC) in the brainstem to activate the voiding re \202 ex. Stimulation of detruso r smooth muscle by parasympathetic cholinergic nerves causes the bladder to contract. Simul tanous activation of nitrergic nerves reduces the intraurethral pressure. Inhibition of som atic input relaxes the external striated sphincter muscle and sympathetic inhi- bition caus es coordinated bladder neck smooth muscle (internal sphinc- ter) relaxation, resulting in b ladder emptying (also see b pp. 596 \200\2237). STORAGE REFLEX VOIDING REFLEX Periaquaductal gray [Pons] Pontine Micturition Center PAG + Brainstem Lumbar spinal cord Intermediolateral cell column \210\222 + Hypogastric nerve Hypogastric nerve Hypogastric ganglion Pelvic nerve + Pelvic nerve + Sacral spinal cord \210\222 + Bladder + + \210\222 ++ + + Int. sphincter Ext. sphincter + Ventral horn Pudendal nerve Pudendal nerve Fig. 18.1 Diagram representing the storage and voiding pathways of the micturition re \202 ex. Micturition is stimulated by activity in the parasympathetic (pelvic) nerves and inhib ited by activity in the sympathetic (hypogastric) nerves and pudendal nerves. CHAPTER 18 Basic science and renal transplant 796 Basic renal anatomy The kidneys and ureters lie within the retroperitoneum (behind the peri - toneal cavity). The hila of the kidneys lie on the transpyloric plane (verte- bral level L1). Each kidney is composed of a cortex surrounding the medulla which forms projections (p apillae) that drain into cup-shaped epithelial-lined pouches called calyces. The calyx drai ning each papilla is known as a minor calyx and several minor calyces coalesce to form a ma jor calyx, several of which drain into the central renal pelvis (Fig. 18.2). The renal arte ry, which arises from the aorta at vertebral level L1/2, branches to form interlobar arteri es which in turn form arcuate arteries, and then cortical radial arter- ies from which the afferent arterioles are derived. Venous drainage occurs into the renal vein. There are two capillary networks in each kidney \200\224a glomerular capillary network (lying within Bowm an \200\231s capsule) which drains into a peritubular capillary network surrounding the tub ules (proximal tubule, Loop of Henle, distal tubule, and collecting ducts). Anatomical relations of the kidney \200 Anterior relations of the right kidney are, from top to bottom, the adrenal (suprarenal) gland, liver, and hepatic \202 exure of the colon . Medially and anterior to the right renal pelvis is the second part of the duodenum. The a nterior relations of the left kidney are, from top to bottom, the adrenal gland, stomach, s pleen, and splenic \202 exure of the colon. Medially lies the tail of the pancreas. Posterior relations of both kidneys are, superiorly, the diaphragm and lower ribs, and infe riorly (from lateral to medial), transversus abdominis, quadratus lumborum, and psoas major muscles. The nephron Each kidney has 1 million functional units or nephrons (Fig. 18.3). These consi st of a glomerular capillary network, surrounded by podocytes (epi- thelial cells) that pro ject into Bowman \200\231s capsule which then drains into a tubular system. This includes a proximal convoluted tubule (PCT), Loop of Henle (LoH), distal convoluted tubule (DCT), col lecting tubule (CT), and collecting duct (CD). Blood is delivered to the glomerular capilla ries by an afferent arteriole and drained by an efferent arteriole. An ultra \201 l- trate of plasma is formed within the lumen of Bowman \200\231s capsule, driven by Starling force s across the glomerular capillaries. Reabsorption of salt and water occurs in the PCT, LoH, DCT, and CD, although the majority of glomerular \201 ltrate is absorbed in the PCT (Tab le 18.1). LoH generates hypertonicity; its descending limb is only permeable to water where as its ascending limb is only permeable to solutes. The role of the DCT is \201 ne adjust ment of the composition of urine by selective reabsorption or secretion of solutes. BASIC RENAL ANATOMY 797 Renal papilla Minor calyx Pyramid Medulla Renal artery Medullary rays Renal vein Cortex Renal pelvis Perirenal fat Major calyx Gerota \200\231s fascia Pararenal fat Ureter Fig. 18.2 Basic renal anatomy. 1 Cortex 2 3 8 KEY: 1 Afferent and efferent arterioles of the glomerulus 2 Bowman \200\231s capsule 3 Prox imal convoluted tubule 4 Loop of Henle (thin descending limb) 5 Loop of Henle (thin ascendi ng limb) 6 Loop of Henle (thick ascending limb) 7 Distal convoluted tubule 8 Collecting tub ule 9 Collecting duct 7 Outer medulla 4 6 9 Inner medulla 5 Fig. 18.3 The nephron. CHAPTER 18 Basic science and renal transplant 798 Table 18.1 Solute and water reabsorption by different parts of the nephron Solute PCT LoH DCT CD Sodium 66% 25% (in TAL) 5% 5% under control of aldosterone Potassium Majority Reabsorption by intercalated cells; secretion by principle cells ADH \206\221 permeability to water Water 66% (by osmosis) Magnesium 80% <5% Phosphate 90% Calcium 60% passive transportation 20% 10% active transportation Bicarbonate Majority Glucose Majority Amino acids Majority PCT=proximal convoluted tubule; LoH=Loop of Henle; TAL=thick ascending limb (of Loop of Hen le); DCT=distal convoluted tubule; CD=collection duct. This page intentionally left blank CHAPTER 18 Basic science and renal transplant 800 Renal physiology: glomerular \201 ltration and regulation of renal blood \202 ow Renal plasma clearance Clearance is the volume of plasma that is completely cleared of solute by the kidney per minute. The clearance ratio for a substance indicates the amount of active r eabsorption or excretion (i.e. ratio <1 = actively reabsorbed; >1 = actively excreted). Cle arance of a substance from the plasma can be expressed mathematically as: U V Clearance = (mL/min) P Clearance ratio clearance GFR / where U is the concentration of a given substance in urine, P is its concen- tration in pla sma, and V is the urine \202 ow rate. Glomerular \201 ltration rate (GFR) (see also b p . 38) Glomerular \201 ltration is driven by Starling forces: a hydrostatic pressure gradi ent between capillary and Bowman \200\231s capsule, which favors \201 ltra- tion, and col loid oncotic pressure which opposes \201 ltration. GFR is the clearance for any substance which is freely \201 ltered and is neither reab- sorbed, secreted, nor metabolized by th e kidney. For such a substance, clearance is equivalent to GFR. Where a substance is both \201 ltered at the glomerulus and secreted by the renal tubules, its clearance will be gre ater than GFR. Where a substance is \201 ltered at the glomerulus, but reabsorbed by the renal tubules, its clearance will be less than GFR. Clinically, GFR is estimated using creatinine and is 7125mL/min. Of note, serum creatinine is an insensitive marker of early renal impairment, as GFR needs to fall below 60 \200\2238 0mL/min before a rise in creatinine is seen. GFR is directly related to renal plasma \202 ow (RPF). Experimentally, GFR can be accurat ely calculated by measuring the clearance of inulin (a sub- stance, which is freely \201 ltered by the glomerulus and is neither secreted nor reabsorbed by the kidneys), using the equation: U V \227 P = GFR ( /mL ) min Thus, the volume of plasma from which in 1min the kidneys remove all inulin is equivalent t o GFR. Factors affecting the GFR are: - Rate of blood \202 ow through the glomerulus. - P ermeability of glomerular capillary wall (K). - Surface area of glomerular capillary bed (S ). - Differences in hydrostatic pressure between glomerular capillary lumen (Pgc) and Bowman \200\231s space (Pt). Differences in oncotic pressure between glomerular capillary ( \200 gc) and t) (although autoregulation of blood \202 ow tends Bowman \200\231s space ( \200 GLOMERULAR FILTRATION AND REGULATION 801 to keep GFR constant despite a varying range of incoming perfusion pressures). This can be represented by the equation: = KS([ GFR (single nephron) KS P \210\222 [ \210\222 [ \200 \200 \210\222 t P gc ] ] ] ) t g g c Normally about one- \201 fth (120mL/min) of the plasma that \202 ows through the glomeru lar capillaries (600mL/min) is \201 ltered ( \201 ltration fraction = GFR/RPF).