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). Renal blood \202 ow (RBF) The kidneys represent <0.5% of body weight, but they receive 25 % of cardiac output (71300mL/min through both kidneys; 650mL/min per kid- ney). Combined bl ood \202 ow in the two renal veins is about 1299mL/min and the difference in \202 ow ra tes represents the urine production rate (i.e. 71mL/min). Autoregulation of RBF RBF is de \201 ned as the pressure difference between the renal artery and renal vein divided by the renal vascular resistance. The glomerular arteri- oles are the major determinants of vascul ar resistance. RBF remains essen- tially constant over a range of perfusion pressures (780 \200\223180mmHg, i.e. RBF is autoregulated). Autoregulation requires no innervation and pro b- ably occurs via: - A myogenic mechanism: increased pressure in the afferent arterioles causes them to contract, thereby preventing a change in RBF. Tubuloglomerular feedback: the \202 ow rate of tubular \202 uid is sensed at the macula densa of the juxtaglomerular apparatus (JGA) and in some way, this controls \202 ow thro ugh the glomerulus to which the JGA is opposed. Other factors that in \202 uence RBF Neural mechanisms Sympathetic nerves innervate the gl omerular arterioles. A reduction in circulating volume (such as blood loss) can stimulate s ympathetic nerves, causing the release of noradrenaline (NA) (which acts on A1-adrenoceptor s on the afferent arteriole) to cause vasoconstriction. This results in reduced RBF and GFR . Endocrine and paracrine mechanisms - Angiotensin II constricts efferent and afferent arteri oles and reduces RBF. ADH, ATP, and endothelin all cause vasoconstriction and reduce RBF and GFR. Nitric oxide causes vasorelaxation and increases RBF. - Atrial natriuretic peptide (ANP) ca uses afferent arteriole dilatation and increases RBF and GFR. CHAPTER 18 Basic science and renal transplant 802 Renal physiology: regulation of water balance Total body water (TBW) is 42L. It is containe d in two major compart- ments \200\224the intracellular \202 uid (ICF or the water inside cells) which accounts for 28L and the extracellular \202 uid (ECF or water outside of ce lls) representing 14L. ECF is further divided into interstitial \202 uid (ISF, 11L), tran scellular \202 uid (1L), and plasma (3L). Hydrostatic and osmotic pressures in \202 uenc e movement between the compartments. Water is taken in from \202 uids, food, and from oxi - dation of food. Water is lost from urine, feces, and insensible losses. Intake and losses usually balance (72L/day) and TBW remains relatively constant. The role of the kidney is r egulation of the volume and composition of ECF by constant adjustment of solutes and water to maintain a normal concentration. ADH or vasopressin ADH is secreted from the posterior pituitary in response to stimulus fro m changes in plasma osmolarity (detected by osmoreceptors in the hypotha- lamus) or changes in BP or volume (detected by baroreceptors in the left atrium, aortic arch, and carotid si nus). These changes also stimulate the thirst center in the brain. The action of ADH on the kidney: Increases CD permeability to water (via aquaporin water channel proteins) and urea. Increases LoH and collecting duct reabsorption of sodium chloride (NaCl). Vasoconstriction. During conditions of water excess Body \202 uids become hypotonic and A DH release and thirst are sup- pressed. In the absence of ADH, the CD is impermeable to wat er and a large volume of hypotonic urine is produced so restoring normal plasma osmolarity. During conditions of water de \201 cit Body \202 uids are hypertonic and ADH secretion a nd thirst are stimulated. The CD becomes permeable, water is reabsorbed into the lumen, and a small volume of hypertonic urine is excreted. The ability to concentration or dilute urine depends on the countercur- rent multiplication system in the LoH. Essentially, a medullary concentra- tion gradient is generated (partly by the active transportation of NaCl), which provides the osmotic driving force for the rea bsorption of water from the lumen of the collecting duct when ADH is present. Children have a circadian rhythm in ADH secretion \216 high at night and low during the day . Adults essentially have a constant ADH secretion over a 24h period, with slight increases occurring around meal times. At these times, increased ADH secretion probably acts to prev ent sudden increases in plasma osmolarity that would otherwise occur due to inges- tion of solutes in a meal. RENAL PHYSIOLOGY: REGULATION OF NA+ AND K+ EXCRETION 803 Renal physiology: regulation of sodium and potassium excretion Sodium regulation NaCl is th e main determinant of ECF osmolality* and volume. Two-thirds of sodium (Na+) is reabsorbed in the PCT by either primary active trans- port (Na+-K+-ATPase pump which transports Na+ in and potassium (K+) out) or by secondary active transportation (specialized Na+ channels al low Na+ in and transfer of other solutes in and out of the cell). Low-pressure receptors in the pulmonary vasculature and cardiac atria and high-pressure bar oreceptors in the aortic arch and carotid sinus rec- ognize changes in the circulating volu me. Decreased blood volume triggers increased sympathetic nerve activity and stimulates ADH secretion, which results in reduced NaCl excretion. Conversely, when blood volumes are inc reased, sympathetic activity and ADH secretion are suppressed and NaCl excretion is enhance d (natriuresis). A variety of natriuretic peptides have been isolated which cause a natriur esis. Under physiological conditions, renal natriuretic peptide (urodilatin) is the most im portant of these. ANP, released after atrial distension, may in \202 uence sodium output u nder condi- tions of heart failure (acting to increase excretion of NaCl and water). Renin \200\223angiotensin \200\223aldosterone system Renin is an enzyme made and stored in the juxtaglomerular cells found in the walls of the afferent arteriole. Factors increasing renin secretion are: - Reduced perfusion of afferent arteriole. - Sympathetic nerve activit y. - Reduced Na+ delivery to the macula densa. Renin acts on angiotensin to create angioten sin I. This is converted to angi- otensin II in the lungs by angiotensin-converting enzyme (ACE). Angiotensin II performs several functions which result in the retention of salt and water: - Stimulates aldosterone secretion (resulting in NaCl reabsorption and promotes secretion of K+ and H+). Vasoconstriction of arterioles. - Stimulates ADH secretion and thirst. - Enhances NaCl reab sorption by the proximal tubule. Potassium regulation K+ is critical for many cell functions. A large concentration gradient across cell membranes is maintained by Na+-K+-ATPase pump. Insulin and adren- aline also p romote cellular uptake of K+. The majority of K+ is reabsorbed in the PCT. The DCT can both rea- bsorb K+ in cases of K+ depletion (intercalated cells) and secrete it when there is K+ excess (principal cells). It is also secreted by the CD. Overall, the kidney excretes up to 95% of K+ ingested in the d iet. Factors promoting K+ secretion include: Increased dietary K+ (driven by the electrochemical gradient). - Aldosterone. - Increased r ate of \202 ow of tubular \202 uid. - Metabolic alkalosis (acidosis exerts the opposite effect). Osmolality = mol/kg water; osmolarity = mol/L of solution. CHAPTER 18 Basic science and renal transplant 804 Renal physiology: acid \200\223base balance The normal pH of ECF is 7.4 ([H+] = 40nmol/L). Several mechanisms are in place to eliminate acid produced by the body and maintain body pH within a narrow range. Buffering systems that limit [H+] \202 uctuation in the blood Buffer bases that take up H + ions in the body include: Bicarbonate buffer system: Phosphate system: Protein buffers: \206\220 \206\222 \206\220 \206\220 \206\220 \206\222 \206\220 \206\220 \200\223 H+ + HCO3 \206\220 \206\222 \206\220 \206 \220 2 \200\223 H+ + HPO4 \206\220 \206\222 \206\220 \206\220 H+ + Protein \200\223 H2CO3 \200\223 H2PO4 HProtein H2O + CO2 The Henderson \200\223Hasselbalch equation describes the relationship between pH and the co ncentration of conjugate acid and base. \210\222 [HCO ] pCO2 = + 3 pH 6 1 log 0 03 From this equation, it can be seen that alterations in bicarbonate \200\223) or CO2 will a ffect pH. Metabolic acid \200\224base disturbances relate (HCO3 \200\223 and respiratory a cid \200\224base disorders relate to to a change in HCO3 alterations in CO2. Bicarbonate reabsorption along the nephron (Fig. 18.4) Bicarbonate is the main buffer of EC F and is regulated by both the kid- neys and lungs. Eighty- \201 ve percent is reabsorbed in the PCT. Carbonic acid is \201 rst produced from CO2 and water (accelerated by carboni c anhy- drase). The carbonic acid dissociates and an active ion pump (Na+/H+ anti- porter) extrudes intracellular H+ into the tubule lumen in exchange for Na+. Secretion of H+ ions f avors a shift of the carbonic acid \200\223bicarbonate equilibrium towards carbonic acid wh ich is rapidly converted into CO2 and water. CO2 diffuses into the tubular cells down its d iffusion gradient and is reformed into carbonic acid by intracellular carbonic anhydrase. \200\223 formed by this reaction is exchanged for chloride and passes The HCO3 into the cir culation. Essentially, with each H+ ion that enters the kidney, a \200\223 ion enters the blood, which bolsters the buffering capacity of the HCO3 ECF. The remaining bicarbonate is absorbed in the DCT where cells actively secrete H+ into the l umen via an ATP-dependent pump. The distal tubule is the main site that pumps H+ into the u rine to ensure the complete \200\223. Once the bicarbonate has gone, phosphate ions and re moval of HCO3 ammonia buffer any remaining H+ ions. Abbreviations: H2O = water; CA = carbonic anhydrase; Cl \200\223 = chloride ion; CO2 = carb on diox- 2 \200\223 = phosphate ions; ide; HCO3 H2PO4 \200\223 = bicarbonate; H2CO3 = carbonic acid; H+ = hydrogen ion; HPO4 \200\223 = phosphoric acid; Na+ = sodium ion; Pco2 = partial pressure of CO2 RENAL PHYSIOLOGY: ACID \200\223BASE BALANCE 805 Plasma Tubule cell Tubule lumen H2O + CO2 H2O + CO2 Carbonic anhydrase CA H2CO3 H2CO3 \200\223 HCO3 Cl \200\223 \200\223 + H+ \200\223 H+ + HCO3 HCO3 Na+ Fig. 18.4 Diagram showing bicarbonate reabsorption in the proximal convoluted tubule. CHAPTER 18 Basic science and renal transplant 806 Renal replacement therapy Indications for dialysis - Chronic kidney disease (CKD) stage 5 ( eGFR 10 \200\22315mL/min). - Acute renal failure due to persistent hyperkalaemia, metabolic acidosis, \202 uid overload, symptomatic uraemia, sepsis, and multiorgan failure, drug o r toxin poisoning. Haemodialysis Access: arteriovenous \201 stula (requires 8 weeks to mature). Principles: the dialysis machine pumps blood and dialysate through a dialy- ser. Dialysate is composed of water, sodium, potassium, dextrose, calcium, chloride, magnesium, and bicarb onate or acetate (as a buffer). The \202 uids are on opposite sides of a semi-permeable m embrane and pumped in opposite directions (countercurrent \202 ow). Waste products of met abolism diffuse from blood to dialysate. Accumulated \202 uid is removed by convec- tion of water and dissolved solutes (including proteins) down a pressure gradient (ultra \201 l tration). Heparin is used to prevent clotting. Regimen: 4h sessions performed three times per week in a hospital-based dialysis unit or at home. Complications: Anemia, cardiovascular disease (hypertension, arrhyth- mias, MI, PVD, CVA), acquired renal cystic disease and renal tract cancers, renal osteodystrophy, neuropathy, er ectile dysfunction. Fistula problems include thrombosis, stenosis, aneurysm, and infection. Peritoneal dialysis Access: Tenckhoff catheter which allows instillation of \202 uid into the peritoneum. Principles: \202 uid and solute exchange occur between peritoneal capillary blood and dia lysis solution using the peritoneum as the dialysis membrane. Small molecular weight solute s diffuse down a concentration gradient from the blood into the dialysate. Water movement i s achieved by osmo- sis from the ECF compartment to the hypertonic peritoneal dialysate. Regimen: continuous ambulatory dialysis (CAPD) involves continuous dial- ysis using 3 \200 \2235 exchanges per day of \202 uid, performed at home. Automated peritoneal dialysis (AP D) allows fast instillation and drainage of large vol- umes of \202 uid if more intense d ialysis is needed or for dialysis overnight. Contraindications: bowel adhesions, obesity, inoperable hernias, stoma. Complications: as for haemodialysis and also catheter infection, peritonitis, membrane (per itoneal) failure, hernia. Haemo \201 ltration Access: intravascular (tunneled) catheters, placed in femoral or inter nal jugular veins. RENAL REPLACEMENT THERAPY 807 Principle: removal of solutes with water is achieved by convection down a pressure gradient . It does not require dialysate. Large volumes of \201 l- trate are removed and need to b e replaced during this process. This is a controlled and slow process, avoiding large intra vascular \202 uid shifts and minimizing electrolyte disturbances, arrhythmias, and hypote nsion. It is particularly useful for the haemodynamically compromised patients with acute r enal failure. Anticoagulation is required. Regimen: blood is \201 ltered continuously across a highly permeable syn- thetic membrane . Complications: similar, but lower, incidence than for haemodialysis. Includes thrombosis of catheter or access vein, bleeding or clotting, sepsis, \202 uid overload, alkalosis, hyp otension. Haemodia \201 ltration This describes the combination of dialysis and ultra \201 ltration (diffusion and convection removal of solutes). CHAPTER 18 Basic science and renal transplant 808 Renal transplant: recipient Indications for transplant End-stage renal disease. Contraindication to renal transplant - Active malignancy is a contraindication to receiving immunotherapy. Generally should remain cancer-free for 2y before transplantation can be co nsidered. Higher risk tumors, including melanoma, breast, colorectal carcinoma, must be dis ease-free for longer (5y). Lower risk tumors of the skin (basal and squamous cell carcinoma ) can undergo transplantation immediately after treatment. Active infection (bacterial and viral, including hepatitis B and C, HIV, CMV, and TB). - Severe vasculitis. - Signi \201 cant cardiovascular disease (including rec ent MI). - Active systemic lupus erythematosus (SLE). - Primary hyperoxaluria (requires com bined renal and liver transplant). - Untreated psychological disorders, IV drug use, or alc ohol excess. Genitourinary tract assessment - USS of kidneys, ureters, and bladder. - Urine analysis and cultures. \200 Urodynamic studies for LUTS (if clinically indicated). Preoperative assessment - History: including cause and length of time of renal failure, pre vious interventions for renal impairment, and previous transplants. Coexisting conditions such as diabetes mellitus (which might require pancreatic transplant). Symptoms of voiding dysfunc tion which will require treatment before transplant. Physical examination. - Cardiology workup: stress test and ECG. - Bloods: FBC, U & E, LFT, glucose, calcium, magnesium, clotting, viral serology (HIV, hepatitis, CMV, syphilis, EBV, HTLA). ABO blood group. - Tissue typing for HLA-A, B, and DR phenotypes. - Blood cross-match to de tect preformed antibodies. Recipient \200\231s sera are mixed with donor lymphocytes. Recip ient antibodies will bind to and lyse donor cells if the cross-match is positive. This page intentionally left blank CHAPTER 18 Basic science and renal transplant 810 Renal transplant: donor Types of donor - Cadaveric (heart beating): brainstem-dead* donor w ith supported ventilation and circulation. Cadaveric (non-heart beating): rapid retrieval is required to minimize ischaemia from these patients without active circulation. Living-related. - Live unrelated: donation must comply with regulations set by the Unrelated Live Transplant Regulatory Authority (ULTRA). Absolute contraindications - Active malignancy. - History of metastatic cancer or cancer wi th a higher recurrence risk (i.e. lymphoma). Signi \201 cant cardiac disease (previous MI, coronary artery bypass graft (CABG), angina). Diabetes, hypertension, signi \201 cant pulmonary or vascular disease. - Active systemic r enal disease, i.e. SLE. - HIV or other active infection. - BMI >35. - Coercion. - Inability to give consent. - IV drug or alcohol abuse. - Pregnancy. Assessment of donor - History: including family history of disorders such as glomerulonephropathies, PCKD, SLE). Clinical and psychological evaluation in living donors, BP check. Bloods: FBC, U&E, cholesterol, glucose, clotting. - ABO and HLA compatibility: Kidneys shou ld be allocated to the recipient with the lowest number of HLA mismatches. Viral serology (hepatitis B and C, HIV, CMV, EBV, syphilis, TB): Establish any family history of high-risk renal disease or prion disease (Creutzfeldt \200 \223Jacob). eGFR (24h urine collection or EDTA in living donors). - ECG and CXR. - Renal imaging to ass ess donor anatomy, choose the kidney (leave the donor with the better kidney), and plan technique. Living donors - Higher success rates than deceased donors and shortens waiting times. - Lon g-term follow-up of donor is recommended for surveillance of hypertension or renal impairment. Full informed consent should be taken. Risks of nephrectomy include: hypertension, chronic renal failure, mortality (<0.03%). RENAL TRANSPLANT: DONOR 811 Brainstem death: requires two sets of test by two doctors (registered for >5y). The criteri a include absence of: corneal re \202 ex, cranial nerve motor function, vestibulo-ocular r e \202 ex, cough and gag re \202 ex. Pupils are \201 xed and unresponsive, no spontaneo us movement, and apnoea off ventilator (PaCO2 >6.7kPa) CHAPTER 18 Basic science and renal transplant 812 Transplant surgery and complications Technique for donor removal The kidney, ureter, vena c ava, aorta, and renal vessels may be taken en bloc from a cadaveric donor. Transportation m ediums include University of Wisconsin preservation solution (with glutathione and adenosin e) with the graft, then packed in ice. Living donor kidney and ureter may be har- vested vi a a laparoscopic or open approach. Surgery The renal graft is most commonly placed into the iliac fossa and the ves- sels anas tomosed to the external iliac vein and artery (alternatives include common iliac vessels). An extravesical ureteric reimplantation is per- formed and a ureteric stent inserted. Immunosuppression after renal transplantation Immunosuppression is used as prophylaxis agai nst graft rejection. Agents utilized include: - Calcineurin inhibitors (CNI), cyclosporin o r tacrolimus, which inhibit IL-2 production. Blood level monitoring is required. Mycophenolate (MPA). - Corticosteroid (prednisolone or methylprednisolone). - Azathioprine, an antimetabolite producing bone marrow suppression. - mTOR. - Antithymocyte globulin (ATG ), a polyclonal antibody which can lyse human leucocytes. OKT3, a monoclonal antibody directed against T lymphocytes. - Rapamycin, an mTOR inhibitor, involved in IL-2 downregulation. Common regimens include CNI, MPA, and corticosteroid. Ste roids can be stopped at 3 \200\22312 post-surgery for patients on combination of CNI and MP A. Azathioprine is an alternative to MPA in low-risk patients. The con- sent process should include the need for long-term immunosuppression and explanation of the related side effec ts (increased risk of malignancy, infection, diabetes, hypertension, tremor, renal and live r problems, oste- oporosis, etc.). Post-operative management - Monitor \202 uid balance with input and output charts and dai ly weights. - Radionuclide renal scan to assess graft blood \202 ow and exclude extravasation. Removal of catheter at 7 days if no extravasation. - Antiplatelet inhibitors (aspirin, dipy ridamole). - Antibacterial and antifungal prophylaxis. - Avoid NSAIDs and ACE inhibitors. - Be wary of drug interaction and alter doses of drugs accordingly. Complications Graft dysfunction can occur early or late and may be due to medical or surgic al causes. TRANSPLANT SURGERY AND COMPLICATIONS 813 Rejection This manifests as renal function deterioration (oliguria, rising creatinine, hype rtension, and proteinuria). Patients may be asymptomatic, have sys- temic symptoms (fever), or local symptoms, including graft tenderness or swelling. Investigate with percutaneous r enal biopsy. - Hyperacute rejection (intraoperatively or within days): due to preformed antibodies to allograft MHC. Treatment is graft removal. Accelerated rejection (within \201 rst week): due to cellular presensitization. Treatment is intensive antirejection treatment, with temporary dialysis s upport. Acute allograft rejection (occurs in the \201 rst 3 months): affects around 20 \200\22330% (90% respond to steroids). Classi \201 ed as acute cellular rejectio n (ACR) which is T-cell-mediated or acute humoral rejection (AHR) which is antibody-mediate d. ACR: treat with a steroid bolus. If this fails, employ intensi \201 ed immunosuppressio n, conversion to tacrolimus, and T-cell-depleting agents. AHR: steroid bolus, conversion to tacrolimus, and IV immunoglobulin treatment. Chronic allograft rejection (months to years): is multifactorial and affects around 30%. Treatment options include conversion from CNI to mTOR inhibitor, or CNI reduction with MPA 9 steroid cover. Other - Post-transplant malignancy. Most affect the skin (40%) or lymphatic system (11%). Graft loss due to recurrence of original renal disease. - Urinary tract: urinary leak, uret eric stricture/obstruction, \201 stula, stones, perinephric collections (lymphocele, haematoma, urinoma, abscess). Vascular complications: renal artery stenosis or thrombosis, renal vein thrombosis, pseudoaneurysm, A \200\223V \201 stula, atheromatous vascular disease. Drug toxicity. - Infection. - Diabetes (thought to be due to the use of corticosteroids and tacrolimus). - Hypertension. Outcomes Recipient death rate at 12 months is 5%. Graft survival rate is >85% at 1y, 60 \200\22370% at 5y, and 40 \200\22350% at 10y. The best results are with living donors. Long-term follow-up Review every 6 \200\22312 months. Monitor renal function, immunosuppres sion, and side effects. Monitor cholesterol (may be raised due to cyclosporine or rapamycin ). Diabetes control may be dif \201 cult due to steroids. Perform surveillance for the dev elopment of malignancy. This page intentionally left blank 815 Chapter 19 Urological eponyms CHAPTER 19 Urological eponyms 816 Alcock \200\231s canal: canal for the internal pudendal vessels and nerve in the ischiorect al fossa. Benjamin Alcock (b 1801). Professor of Anatomy, Physiology, and Pathology (1837) at the Apothecaries Hall in Dublin. Anderson \200\223Hynes pyeloplasty: dismembered pyeloplasty for PUJO. James Anderson and Wi lfred Hynes. Surgeons, Shef \201 eld United Hospitals. BCG (Bacille Calmette \200\223Gu rin): attenuated TB bacillus used for immu- notherapy of carcinoma in situ of bladder. Leon Charles Albert Calmette (1863 \200\2231933). A pupil of Pasteur in Paris, later becoming \201 rst director of Pasteur Institute. Camille Gu rin (b 1872). A veterinary surgeon at the Calmette Institute in Lille who, along with Calmette, developed BCG vaccine. Bonney \200\231s test: elevation of bladder neck during vaginal examina- tion reduces leaka ge of urine during coughing (used to diagnose stress incontinence). William Bonney (1872 \200\2231953). Studied at Barts and Middlesex Hospitals. On the staff of Royal Masonic Hosp ital and Chelsea Hospital for Women. A highly skilled surgeon with an international reputat ion. Bowman \200\231s capsule: epithelial-lined \200\230cup \200\231 surrounding the glomerulus in the kidney. Sir William Paget Bowman (1816 \200\2231892). Surgeon to Birmingham General Hospital. Elected FRS in 1841. FRCS 1844. Won the Royal Medal of the Royal Society for his description of the Malpighian body of the kidney. He proposed the theory of urine producti on by \201 ltration of plasma. Described as the father of histology. In 1846 became surge on to Moor \201 elds Eye Hospital. An early proponent of the ophthalmoscope and the \201 rst in England to treat glaucoma by iridectomy (1862). Camper \200\231s fascia: super \201 cial layer of super \201 cial fascia (fat) of abdomen and inguinal region. Pieter Camper (1722 \200\2231789). Physician and anatomist in Leyden, The Netherlands. Charri re system: system of measurement for \200\230sizing \200\231 catheters and stents. Joseph Charri re (1803 \200\2231876). Surgical instrument maker in Paris. Clutton \200\231s sounds: metal probes for dilating the urethra (originally used for \200 \230sounding \200\231 for bladder stones). Henry Clutton (1850 \200\2231909). Surgeon to St .Thomas \200\231s Hospital, London. UROLOGICAL EPONYMS 817 Colles fascia: super \201 cial fascia of the perineum. Abraham Colles (1773 \200\2231843). Professor of Anatomy and Surgery in Dublin. Denonvilliers fascia: rectovesical fascia. Charles Denonvilliers (1808 \200\2231872). Profe ssor of Anatomy, Paris and later Professor of Surgery. Dormia basket: basket for extracting stones from the ureter. Enrico Dormia. Assistant Profe ssor of Surgery, Milan. Douglas, Pouch of: rectouterine pouch (in females), rectovesical pouch (in males). James Do uglas (1675 \200\2231742). Anatomist. Physician to the Queen. Foley catheter: balloon catheter, designed to be self-retaining. Foley pyeloplasty Frederic Foley (1891 \200\2231966). Urologist, St Paul \200\231s, Minneso ta. Fournier \200\231s gangrene: fulminating gangrene of external genitalia and lower abdominal wall. Jean Fournier (1832 \200\2231914). Professor of Dermatology, H pital St Louis, Pari s. Also recognized the association between syphilis and tabes dorsalis. Gerota \200\231s fascia: the renal fascia. Dumitru Gerota (1867 \200\2231939). Professor of Surgery, University of Budapest. (Loop of) Henle: U-shaped segment of the nephron between the proxi- mal and distal convolut ed tubules. Friedrich Henle (1809 \200\2231885). Professor of Anatomy, Zurich and G ttinge n. von Hippel \200\223Lindau syndrome: syndrome of multiple renal cancers. Eugen von Hippel (1 867 \200\2231939). Ophthalmologist in Berlin. Arvid Lindau (b 1892). Swedish pathologist. Hunner \200\231s ulcer: ulcer in bladder in interstitial cystitis. Guy Hunner (1868 \200 \2231957). Professor of Gynecology, Johns Hopkins. Jaboulay procedure: operation for hydrocele repair (excision of hydro- cele sac). Mathieu J aboulay (1860 \200\2231913). Professor of Surgery, Lyon. Klinefelter \200\231s syndrome: male hypogonadism with XXY chromosome complement. Harry Kli nefelter (b 1912). Associate Professor of Medicine, Johns Hopkins. CHAPTER 19 Urological eponyms 818 Kockerization of the duodenum: mobilization of the 2nd part of the duo- denum. Used to expo se the inferior vena cava and right renal vein during radical nephrectomy. Emil Kocker (184 1 \200\2231917). Professor of Surgery, Berne University. A founder of modern surgery. Won t he Nobel Prize in 1909 for work on the physiology, pathology, and surgery of the thyroid gl and. Lahey forceps: curved forceps used during surgery. Frank Lahey (1880 \200\2231953). Head of Surgery, Lahey Clinic, Boston. Langenbeck retractor: commonly used retractor during surgery. Bernard von Langenbeck (1810 \200\2231887). Professor of Surgery, Kiel and Berlin. A great teacher and surgeon. Leydig cells: interstitial cells of the testis. Franz von Leydig (1821 \200\2231908). Profe ssor of Histology, W rtzburg, T bingen, Bonn. Mal cot catheter: large bore catheter, used for drainage of kidney fol- lowing PCNL. Achil le Mal cot (b 1852). Surgeon in Paris. Millin \200\231s prostatectomy: retropubic open prostatectomy. Terence Millin (d 1980). Iri sh surgeon, trained in Dublin. Surgeon at Middlesex and Guy \200\231s Hospitals and later, Westminster Hospital. Became President of the British Association of Urological Surgeons an d then President of the Royal College of Surgeons of Ireland. Peyronie \200\231s disease: \201 brosis of shaft of penis, causing a bend of the penis du ring erection. Fran ois Peyronie (1678 \200\2231747). Surgeon to Louis XV in Paris. Pfannenstiel incision: suprapubic incision used for surgery to the bladder and uterus. Herm ann Pfannenstiel (1862 \200\2231909). Gynecologist from Breslau. (Cave of ) Retzius: prevesical space. Andreas Retzius (1796 \200\2231860). Professor of Ana tomy and Physiology at the Karolinska Institute, Stockholm. Santorini \200\231s plexus: plexus of veins on the ventral surface of the prostate. Giandom enico Santorini (1681 \200\2231738). Professor of Anatomy and Medicine in Venice. Wrote a g reat work on anatomy, Observationes anatomicae, published in Venice in 1724. Scarpa \200\231s fascia: deep layer of the super \201 cial fascia of the abdominal wall. A ntonio Scarpa (1747 \200\2231832). Professor of Anatomy in Modena and Pavia. Sertoli cells: supportive cells of testicular epithelium. Entrico Sertoli (1842 \200\223191 0). Professor of Experimental Physiology, Milan. Trendelenburg position: head down operating position. Friedrich Trendelenburg (1844 \200 \2231924). Langenbeck \200\231s assistant in Berlin and was then Professor of Surgery at Ro stock, Bonn, and then Leipzig. UROLOGICAL EPONYMS 819 Weigert \200\231s law: inverse position of ectopic ureter (the ureter of the upper moiety o f a duplex system) drains distally into the bladder (or below into the urethra), whereas th e lower pole ureter drains into a proximal posi- tion in the bladder. Carl Weigert (1845 \200\2231904). German pathologist. Wilms \200\231 tumor: nephroblastoma of kidney. Max Wilms (1867 \200\2231918). Surgical ass istant to Trandeleburg in Leipzig and subsequently Professor of Surgery in Leipzig. Later, Professor of Surgery in Basle and Heidelberg. Young \200\231s prostatectomy: perineal prostatectomy. Hugh Hampton Young (1870 \200\223194 5). Professor of Urology, John Hopkins School of Medicine. 820 Index A abdominal distension 29 abdominal anterior urethral strictures 124 ballistic lithotripsy 450, 451 BCG 280, 816 Beh et \200\231s syndrome 232 benign prostatic hyperplasia anterior wall prolapse 170 antibiotics examination 28 \200\2239 abiraterone 359, 360 abscess pre-operative 702 \200\2233, 704 prescribing in (BPH) alpha blocker therapy 86 androgens 72 anticholinergic therapy 92 bladder outlet pregnancy 643 UTI prophylaxis 187 \200\2238 anticholinergic therapy 92, perinephric 192 \200\2233 peri-urethral 204 prostatic 211 psoas 33 148 obstruction 73 characteristics 72 clinical practice guidelines 76 antidiuretic hormone acid-base balance 804 \200\2235 acquired immunode \201 ciency (ADH) 802 antiplatelets 699 apomorphine 576 arteriovenous \201 stula 517, syndrome 226 acquired renal cystic disease 402 \200\2233 combination therapy 90 diagnostic tests 76 high intensity focused 518 Acucise 413 acute bacterial arti \201 cial heart valves 702 arti \201 cial urinary ultrasound (HIFU) 95 invasive surgical prostatitis 210 acute epididymitis 206 acute loin pain 20 \200\22321 acute pyelonephritis 1 76, sphincter 146, 147, 625, 627 aspirin 699 assisted conception 565 assisted reproductive tech niques 565 atypical small acinar proliferation 330 alternatives to TURP 96 laser prostatectomy 96 \200\2237, 98 190, 193, 642 minimally invasive surgery 94