Renal (Classroom Notes)

Renal & Urology Notes Anatomy & Physiology       Anatomy & Histology in relation to function Glomerular filtration & Renal plasma flow Tubular function Acid-Base regulation Diuretics Disorders of fluid and electrolyte imbalance 2 9 12 17 19 20 Clinical              Renal failure Acute renal failure Chronic renal failure Nephrotic syndrome Glomerulonephritis Obstructive conditions of the kidney & ureters Urinary Calculi Neoplastic conditions of the kidney & ureters The bladder & prostate Continence UTI Sexually transmitted infections The urethra, penis & scrotum Na+ K+ Ca2+ Creatinine Urea Albumin Proteins 23 24 26 31 32 33 34 37 41 45 47 49 53 135 –145 mmol / L 3.5 – 5.0 mmol / L 2.12 – 2.65 mmol / L 70 – 150 μmol / L 2.5 – 6.7 mmol / L 35 – 50 g / L 60 – 80 g / L Cardiac output 5l/min PCV = 40% (Blood = approx 5l = 3l plasma & 2l red cells) Renal blood flow 1l/min Renal plasma flow (RPF) = 600ml/min GFR = 120ml/min (efferent plasma flow = 480ml/min) Reabsorption = 119ml/min  Urine output < 1ml/min >150mg protein / 24 hrs in urine is abnormal Renal 1 Anatomy of the urogenital system  Kidneys Lie retroperitoneally on posterior abdominal wall T12-L3 Right kidney sits lower due to lobe of liver Relations Inferior to diaphragm (through to 12th ribs & pleura) & suprarenal glands Anterior to quadratus lumbrorum muscle, subcostal nerves & vessels & hypogastric & ilioinguinal nerves Posterior to liver duodenum & asc. colon (on right), stomach, spleen pancreas, jejunum & desc colon (on left). Structures at hilum Anterior = renal vein Several draining veins unite to form the renal vein LHS passes anterior to the aorta Medial = renal artery Arises from aorta at level L1-L2 & RHS passes posterior to IVC Each AA divides to 5 segmental end arteries (no anastomosis) (5 segments are superior, anterosuperior, anteroinferior, posterior, inferior) Posterior = renal pelvis & ureter Lymphatic drainage Follows the renal veins  lumbar lymph nodes Nerve supply – shared with ureters From renal plexus Sympathetic, parasympathetic & visceral afferent fibres Renal Cortex Fibrous Capsule Minor Calyces Vessel in Parenchyma Renal Pyramid (medulla) Renal Sinus Major Calyces Renal Papilla Renal Pelvis Renal Column (of Bertin) Fat in Renal Sinus Medullary Rays Base of Renal Pyramid Minor Calycyes Ureter Renal 2 Vitamin D metabolism Calciferol is hydroxylated by renal enzymes Enzyme activity increased by parathyroid-hormone & reduction in end product If enzyme inactive  decreased Ca & PO4 absorption  impaired bone & metabolism Renal impairment  decreased Ca2+ absorption  increased PTH  hyperparathyroidism  Suprarenal gland On superomedial aspect of kidneys Separated by weak septum of connective, perinephric fat and renal fascia (by which the are attached to the crura of diaphragm Left side – semilunar shaped, Right side – triangular shaped  Renal fascia & fat The kidney is surrounded by the renal fascia (outer) and perirenal fat (inner) There is then a collection of pararenal fat (external to the renal fascia) mostly posterior The fat allows movement of the kidneys during respiration The renal fascia sends bundles of collagen through the fat to anchor the kidney Perinephric abscess The attachments of the fascia determine the path of spread of an abscess Spread to the contralateral side is unlikely Spread down into the pelvis following the ureters is common (of pus or blood)  Ureters Lined with transitional squamous epitheium so able to withstand toxicity of urine Muscular ducts with narrow lumen Begin as pelvis (merging of major calices) Run inferiorly from the kidney retroperitoneally Pass over pelvic brim at the level of the bifurcation of the common iliac arteries Then run along lateral wall of pelvis (in women crossed by uterine artery) Enters bladder posteroinferior Abdominal parts adhere closely to parietal peritoneum Blood supply Arteries from renal, gonadal and abdominal aorta Veins to renal and gonadal Lymphatic drainage Superior – join with renal drainage  aortic lymph nodes Middle – drain to common iliac nodes Inferior – drain to common, external or internal nodes Innervation Adjacent autonomic plexuses (renal, aortic, sup & inf hypogastric) Pain fibres run to T11-L1/2  Bladder Separated from pubic bones by retropubic space Lies inferior to the peritoneum (rests on pelvic floor) Surrounded by extraperitoneal fatty tissue Only strongly anchored at neck – by puboprostatic/pubovesical ligaments When empty sits in lesser pelvis, when full can reach umbilicus Wall of the bladder is detrussor muscle Ureters enter bladder obliquely so increase in bladder pressure  shuts off ureters  prevents reflux Renal 3 In males At neck fibres form internal involuntary sphincter Fibres are continuous with fibromuscular tissue of prostate In females No internal sphincter Blood supply Arterial Branches of Internal iliac arteries supply main body Superior vesical arteries supply anterosuperior parts Small branches from obturator & inferior gluteal AA In men inferior vesical AA supply neck In women vaginal AA branches supply neck Venous drainage Corresponding veins  internal iliac In men the vesical venous plexus merges with prostatic venous plexus to envelop fundus of bladder, prostate, seminal glands, ductus deferens & inferior ureters. Prostatic plexus also receives blood from dorsal vein of penis. The vesical plexus drains to inferior vesical veins  internal iliacs In women the vesical venous plexus surrounds pelvic urethra & neck of bladder, drains dorsal vein of clitoris & empties to vagial/uterine venous plexus Lymphatic drainage Superior surface of bladder  external iliac nodes Inferior surface  internal iliac nodes Innervation Parasympathetic from pelvic splanchnic nerves (motor to detrussor & inhibitor to sphincter – males only) Stimulation of visceral afferent (stretching)  parasympathetic innervation UNLESS continence centre of brain intervenes Sympathetic T11-L2 Renal 4 Nerves all form vesical nerve plexus – continuous with inferior hypogastric plexus  Female urethra Passes anteroinferiorly from internal urethral orifice Runs posterior to pubic symphysis External urethra orifice is in the vestibule of the vagina (anterior to the vagina) Urethral glands are present in superior part & paraurethral glands are similar to prostate Glands all have common paraurethral duct opening near external orifice Blood supply Internal pudendal & vaginal AA Veins are similar Lymphatic drainage Sacral & internal iliac nodes Innervation Arise in pudendal nerve Most afferents are in pelvic splanchnic nerves  Male Urethra Muscular tube from bladder neck to tip of glans Urethra in bladder neck (preprostatic) Vertical from bladder neck to superior aspect of prostate Prostatic Descends through the prostate, gently curving anterior Widest & most dilatable part Ends as surrounded by external urethra sphincter Urethral crest (median ridge on posterior wall) with has seminal colliculus (rounded with slit like orifice (opens into prostatic utricle) with opening of ejactulatory duct on or within the utricle Prostatic sinuses (groves) to each side of crest & most ducts open into these sinuses Intermediate (membranous) Passes through the sphincter & perineal membrane Narrowest & least distensible due to surrounding sphincter Spongy (penile) Blood supply Preprostatic & Prostatic - Prostatic branches of inferior vesical & middle rectal AA Intermediate & Spongy – internal pudendal AA Veins accompany arteries & have similar names Lymphatic drainage Mainly to internal iliac nodes, but from spongy  deep inguinal nodes Innervation Derived from branches of pudendal nerve & prostatic plexus & autonomic NS  Prostate Walnut sized, inverted pyramid shape Dense prostatic capsule surrounded by fibrous prostatic sheath (continuous with puboprostatic ligaments) Lateral lobes (1) Either side of the urethra = MAIN PART OF PROSTATE Anterior lobe (2) anterior to the urethra fibromucsular (muscle is continuation of urethral sphincter) Contains little, if any, glandular tissue Isthmus = narrow part anterior to the urethra Middle (median) lobe (3) Between urethra & ejactulatory ducts Closely related to neck of bladder Indistinct unless hypertrophied Posterior lobe (4) Posterior to urethra & inferior to ejaculatory ducts Renal 5 Easily palpable by digital rectal examination Prostatic ducts (20-30) Open into prostatic sinuses (either side of seminal colliculus) Prostatic fluid = 20% semen volume Blood Supply Prostatic arteries = branches of internal iliac (inf vesical) + int pudendal, middle rectal Veins form prostatic venous plexus (around sides & base) – between sheath & capsule, drains to internal iliac veins. Plexus communicates superiorly with vesical plexus & posterior with internal vertebral plexus Lymph drainage To internal iliac & sacral LN Innervation Parasympathetic = pelvic splanchnic (S2-4) Sympathetic = inferior hypogastic plexus  Bulbourethral glands 2 pea sized Posterolateral to intermediate (membranous) urethra Ducts pass through inferior fascia of sphincter & open in proximal spongy urethra (bulb of penis) Mucus-like secretion enters urethra during arousal  Penis Anatomically divided into root, body & glans Root – crura & bulb, surrounded by ischiocavernosa & bulbospongiosus. Located in superficial perineal pouch. Body – pendulous in flaccid condition Glands – distal expansion of corpus spongiosum. Covered by the prepuce (foreskin) Composed of 2 corpus cavernosa & 1 corpus spongiosum Corpus cavernosa – contain deep arteries, Each is surrounded by tunica albuginea, the pair by the deep fascia of penis  fused in median plane Corpus spongiosum – contains spongy urethra Blood supply Branches of internal pudendal AA Dorsal AA in the interval between corpora cavernosa & penile skin Deep arteries pierce the crura & run in corpus cavernosa supplying erectile tissue Artery of the bulb supplies bulbourethral gland & proximal spongiosum Deep drainage by venous plexus  deep dorsal vein of penis  prostatic venous plexus Skin drained by superficial dorsal vein  superficial external pudendal vein Lymphatic drainage to superficial inguinal LN Renal 6 Innervation S2-4 – terminal branches of the pudendal nerve (skin, glans & spongy urethra)  Inguinal canal Oblique, inferomedial passage between superficial & deep inguinal rings Lies parallel & superior to medial ½ of inguinal ligament Contains the spermatic cord / round ligament + blood, lymph & ilioinguinal nerve Deep internal ring – out-pouching of transversalis fascia 1.25cm superior to middle of inguinal ligament, lateral to epigastric vessels Superficial external ring – slit like opening between diagonal fibres of aponeurosis of external oblique (superolateral to pubic tubercle). The medial & lateral edges of the ring area called medial & lateral crura Anterior wall of canal – external oblique aponeurosis (+ internal oblique in lateral aspect) Posterior wall – transversalis fascia (+ conjoint tendon (= int oblique & tranversus abdominis) medially) Roof – arching fibres of internal oblique & transverse abdominal muscles Floor – superior surface of inguinal ligament  Spermatic cord Ductus deferens & neurovascular structures pass through deep ring (lateral to inferior epigastric vessels) Gains coverings as it transverses the canal and exits the superficial rings Ends in scrotum (at posterior border of testis) Fascial coverings Tunica Vaginalis – only in front of testis – from peritoneum Internal spermatic fascia = transversalis fascia Cremasteric fascia = from fascia of superficial & deep aspects of internal oblique. Inc loops of cremaster muscle (lowermost part of internal oblique, Inn genitofemoral nerve, L1-2) External spermatic fascia = from external oblique aponeurosis Contents of the cord Ductus deferens (vas deferens) – muscular tube carrying sperm to prostatic urethra Testicular artery – from aorta  testis & epididymis Artery of ductus deferens – from inferior vesical artery Cremasteric artery – from inferior epigastric artery Pampiniform plexus – venous network  testicular veins Sympathetic nerve fibres – on arteries (+ sympa & parasympathetic fibres on ductus) Genital branch of genitofemoral nerve – supplying cremaster muscle Lymphatic vessels – drain to lumbar & preaortic nodes  Scrotum Mucocutaneous sac consisting 2 layers Heavily pigmented skin – which is firmly adherant to the… Dartos fascia (layer of smooth muscle fibres) Blood supply (veins accompany arteries) Posterior scrotal artery (terminal branch of internal pudendal) Anterior scrotal artery (terminal branches of external pudendal) Lymphatic drainage – to superficial inguinal nodes Nerves Anterolateral surface - Genital branch of genitofemoral nerve (L1,2) Renal 7 Anterior surface – anterior scrotal nerve (branches of ilioinguinal L1) Posterior surface – posterior scrotal (branches of pudendal S2-4) Lateral surface – posterior femoral cutaneous (S2,3)  Testes Sperm are formed in seminiferous tubules (joined by straight tubes to the rete testis) Surface of each testis is covered by visceral layer of tunica vaginalis (except where epididymis & spermatic cord attaches) Tunica vaginalis is a closed sac – double layered with small amount of straw coloured fluid between Blood supply Testicular arteries arise from abdominal aorta (just below renal AA), run retroperitonally, cross over ureters & inferior external iliac  inguinal canal  run with spermatic cord Pampiniform plexus (from 8-12 small veins). The cooler blood of the plexus takes heat from the artery  keeps the testes lower than body temp Left testicular vein from plexus to left renal vein Right testicular vein from plexus to IVC Lymphatic drainage – to lumbar & preaortic nodes Innervation – autonomic from T7 via plexus on testicular artery Male hormone sequence Hypothalamus + GnRH Anterior pituitary - + LH Leydig cells in testes + Testosterone  5 alpha reductase DiHydroTestosterone (DHT) (4 x more potent) Epididymis Formed by minute convolutions of duct of epiddidymis (compacted to appear solid) Lies on posterior surface of testis, Connects testis to ductus deferens Efferent ductules transport newly formed sperms to rete testis (where stored until mature) Head – superior expanded part composed of 12-14 efferent ductules Body – convoluted duct Tail – transports sperm from epididymis to ejaculatory duct for expulsion into prostatic urethra Renal 8 Glomerular filtration & Renal plasma flow  Describe the functional relationships between vascular and tubular elements within the kidney. Efferent arteriole Glomerular capillaries Afferent arteriole Peritubular capillary plexus Proximal convoluted tubule Peritubular capillaries Distal convoluted tubule Thick ascending limb of the loop of Henle Bowman’s space Descending vasa Bowman’s recta (carry about 1% capsule of renal blood flow) Ascending vasa recta Collecting duct Descending limb of the loop of Henle Thin ascending limb of the loop of Henle Efferent arteriole smaller diameter than afferent Each kidney about 1 x 106 nephrons All the glomeruli are in the renal cortex Nephrons - 85% cortical (short loops), 15% juxtamedullary (long loops)  Give an account of ultrafiltration. & derive an expression for estimating (GFR) Ultrafiltration – no protein is allowed through (keeps π BS at 0mmHg) Glomerular filter: endothelial cells, basement membrane & podocytes Endothelium: fenestrated and freely permeable to water (& many solutes) but –ve charge  repel anionic proteins Molecules are filtered according to size and charge, may also be protein bound Glomerular Capillary Capillary hydrostatic (PGC) Colloid osmotic pressure (πGC) 15 mmHg Net pressure (PUF)     Bowman’s space 60mmHg 25mmHg Bowman’s Space pressure (PBS) 20mmHg GFR = Kf [ (PGC – PBS) – σ(πGC – πBS) ] σ = reflection coefficient for proteins = 1 Kf = filtration coefficient (intrinsic permeability x filtration area)  Describe the attributes of an appropriate indicator substance for calculating GFR Indicator substance should be: Freely filtered (not bound to plasma proteins) Not reabsorbed or secreted Not metabolised (degraded or synthesised) by kidney Renal 9 No effect on renal function (not toxic) Easily measured in urine Therefore mass filtered = mass excreted Inulin = inert polysaccaride (needs to be infused as not made in body) Creatinine can be used but is made in the body [P]i . GFR = [U]i . Vrate GFR = [U]i . Vrate / [P]I  [U] = urine conc [P] = Plasma conc V rate = urine flow rate Describe the attributes of an appropriate indicator substance to calculate RPF & RBF PAH (ParaAminoHippuric acid – is not made in the body) is freely filtered and secreted At low concentrations (0.83 mmol/l) all the PAH presented to the kidney is removed Tm (transport maximum) from PAH secretion is 0.40 mmol/min Total mass PAH excreted = total mass presented to the kidney = plasma concentration x plasma flow rate (RPF) If PAH conc is increased the filtered mass is increased, but the secreted mass cannot increase so UV/P is no longer an estimate of RPF RBF x PCV = RPF  RBF = RPF / PCV Indicate the clinical significance of the plasma concentration and urinary excretion of creatinine and urea. Creatinine (70-150 μmmol/L) Is a by-product of skeletal-muscle creatine metabolism Is produced at a steady rate The amount produced is relative to body muscle mass Is secreted in small amounts by the kidney BUT the measure of concentration is also slightly inaccurate (the other way) SO (in most clinical situations)… Creatinine clearance = GFR = [U]V / [P] Clinically measuring creatinine clearance Collect urine over 24 hr period (void at set time, then collect all urine for next 24 hours Take plasma sample for [creatinine] once during collection NB: beware units [U] = mmol/l, [P] = μmol/l, V=ml (NB 1440 mins in 24hrs) GFR = Clearance = U x (V/1440) / (P/1000) GFR = Clearance = 0.7 x UV/P Normal GFR = 125ml/min Urea (2.5-6.7 mmol/L) Is a waste product of protein metabolism Production depends on diet, body mass & other factors Is freely filtered and partially reabsorbed due to concentration gradients through the loop & collecting ducts If raised is a measure of poor renal function or excess production In excess in the body can cause N&V, oedema, pruritis and other S&S of CRF Renal 10  Give an account of the functional significance of the filtration fraction (GFR/RPF) Filtration fraction = GFR / RPF = 120/600 = 0.2 (20% of the plasma entering is filtered) Higher filtration fraction means higher colloid osmotic pressure in the peritubular capillaries (more filtrate makes the remaining plasma more concentrated) Normal protein conc = 70 g / l Peritubular protein conc = 70 x (0.6 x 0.48) = 87.5g / l (because 120ml fluid filtered) This rise in osmotic pressure enables water reabsorption later in the kidney If 1 litre of blood is lost hydrostatic pressure falls  Shutdown afferent & efferent arterioles has 2 effects  Redirects blood to heart & brain  Maintains hydrostatic pressure required for filtration (efferent shuts more)  If colloid fluid is infused  increase in colloid osmotic pressure  decreases filtration If occlusion to outflow of tubules  Increased Bowman’s space pressure  stop of filtration once PBS > 35 mmHg  Describe the renal handing of glucose Fasting glucose level = 5mmol/l Renal filtration = 180 l/day 5 x 180 = 900mmol glucose filtered / day BUT urine normally has no glucose so 900mmol reabsorbed NB: Tm for glucose reabsorption = 2mmol/min hence if blood glucose raises to high not all can be reabsorbed  glycosuria Recap: Inulin PAH Glucose freely filtered freely filtered and secreted freely filtered and reabsorbed Renal 11 Tubular function  Give estimates of the normal values for plasma concentrations of Na +, K+, Cl-. HCO3-, H+, glucose and protein, of glomerular filtration rate, effective renal plasma (and blood) flow and cardiac output. Total body water = 50% b.wt (male = approx 40l), 60% b.wt (female) Intracellular Extracellular Filtered Excreted Reabsorbed (60%) (40%) mmol / day mmol / day % Water 180 l / day 1.5 l 99.2 Na+ (mmol / l) 12 135-145 25,200 150 99.4 K+ (mmol / l) 150 3.5-5.0 720 100 86.1 Cl- (mmol / l) 5 100-106 4320 2 99.9 HCO3- (mmol / l) 12 21-28 1800 150 99.2 H+ (nmol/l) 37-43 Glucose 3.9-5.6 800 0 100 Plasma proteins 60-84 g/l NB: ultrafiltrate concentrations are similar to plasma except for proteins In 70kg adult PCV = 40% (Blood = approx 5l = 3l plasma & 2l red cells) Cardiac output 5l/min Renal blood flow 1l/min  Renal plasma flow (RPF) = 600ml/min GFR = 120ml/min (efferent plasma flow = 480ml/min) Reabsorption = 119ml/min Peritubular fluid  Urine output < 1ml/min  3Na+ Proximal tubular handling Na+ K+ 70% filtered Na+ reabsorbed Glucose / AA Out of Lumen 30-60% Na+/H+ antiport 10% Na+/Glucose (AA, PO4) co-transport 5-15% Ion channels 25-50% free diffusion Into Peritubular fluid Na+/K+/ATPase (Na Pump) Na+ transporter Glucose / AA transporter Cl- and organic molecules are coupled in transport Water moves to maintain osmotic balance HCO3- Lateral space 2K+ Na+ Glucose (AA, PO4) H+ Na+ (30-60%) Na+ (10%) Na+ (25-50%) Lumen Peritubular fluid 90% filtered HCO3- reabsorbed HCO3- 3Na+ Movement of positive Na ions requires a counter charge to also move The BM is impermeable to HCO3- but will allow water with dissolved CO2 through Carbonic anhydrase on the cell surface drives the conversion The Na+/H+ antiport ensures suffient H+ is available for the reaction 2K+ HCO3H+ H2CO3 CA CO2 + H2O Na+ Lumen Renal 12 Na+ (5-15%) HCO3- CA H2CO3 CO2 + H2O Other Ions (Urea, K+, Cl-) Because the proteins remain in the peritubular fluid an osmotic gradient is created As water moves an gradient is created for the other ions Peritubular fluid 3Na+ Urea Cl- 2K+ Freely filtered But movement of water  passive reabsorption (driven by active Na+ reuptake) H2O Urea ClSome moves here but more moves later in the kidney K+ K+ Active reuptake but not Na+/K+/ATPase  H2O Urea Cl- Lumen Thick ascending limb of the loop of Henle. Peritubular fluid Between the end of the proximal tubule and the start of the thick ascending limb all movement is passive and driven by concentration of peritubular fluid Lumen H2O Na+ 2ClK+ Cl- The thick ascending limb is impermbeable to water K+ 2Cl-/1Na+/1K+ co-transport system removes solute from the thick ascending limb 3Na+ 2K+ Na+/K+/ATPase and Cl-/K+ cotransport system move solute from the cells to the peritubular fluid. 25% of filtered Na+ is reabsorbed here Net result is concentration of peritubular fluid & dilution of filtrate Fluid exiting the proximal tubule is 290 mosmolar Fluid in the thick ascending loop is 180 mosmolar Concentration difference between the descending limb and the peritubular fluid (around the ascending limb) causes osmotic removal of water from descending limb  extremely Peritubular fluid concentrated filtrate in loop of Henle  3Na+ Early distal tubule Ca2+ Cl- Early distal tubule 3Na+ 2K+ Impermeable to water Net efflux of NaCl 6% filtered Na+ reabsorbed here NB: pumps are different to those in the thick ascending limb Ca2+ Na+ ClH2O Renal 13 Lumen  Late distal tubule / cortical collecting duct Net reabsorption of Na+ due to Na+/K+/ATPase Pump generates gradient to pull Na+ into cell from lumen Peritubular fluid 3Na+ H+ actively secreted by proton pumps in intercalated cells. HCO3- Cl- 2K+ CO2 + H2O H+ Aldosterone Principle cell Makes existing pumps more efficient to increase Na+ reabsorption Increases permeability Lumen of Na+ channels in luminal membrane Long term increases production of pumps K+ Intercalated cell Na+ K+ H+ Proton Pump Describe the contributions of thick ascending limb solute reabsorption and urea recycling to the generation of the renal medullary concentration gradient. Na+ H2O 180 mosmol / kg 290 mosmol / kg H2O permeability depends on ADH  insertion of H2O channels  increase uptake Ions Osmotic H2O moves out because high conc of ions in peritubular fluid from the thick ascending limb Blood flow in Vasa Recta prevents high ion concentrations moving into the blood Some passive diffusion of ions into the descending limb H2O ADH has no effect on permeability to urea H2O Because H2O taken up urea becomes highly concentrated H2O Cortical Collecting Duct Medullary Collecting duct O2 CO2 Highly permeable to urea Urea Cells deep in the medulla H2O get low O2, High CO2 & high osmolality – no other cells in the body can survive this 1200 mosmol / kg  CA H2CO3 HCO3- 2% Na+ reabsorbed  Cl- Effector mechanisms influencing Na+ transport RAA system Increases proximal Na+ reabsorption Aldosterone increases late distal / CCD Na+ reabsorption Sympathetic NS Noradrenaline increases proximal Na+ reabsorption Renal 14 Final urine conc = 1200 mosmol / kg because duct runs through tip of loop Activates RAA  increased Na+ reabsorption Atrial Natriuretic Peptide (ANP) Increases GFR (by vasodilatation)  increased Na+ excretion Decreases proximal & MCD Na+ reabsorption Reduces Na+ & H2O reabsorption  reduced blood volume Natriuretic Factors Decrease proximal Na+ reabsorption Inhibit renin release (increase Na+ excretion) Also affects GFR & RPF Loss of Na+ in urine  Describe the components & workings of the renin-angiotensin-aldosterone (RAA) system. Components Macula Densa A modified collection of cells at the junction of the thick ascending loop / distal convoluted tubule. Granular cells Cells in the wall of the afferent arteriole (just before the glomerular capillaries) in close proximity to those of the macula densa The cells have granular inclusions of prorenin in them Juxtaglomerular apparatus = macula densa + granular cells Factors affecting renin release Macula densa Decreased Na+ delivery to distal tubule  increased renin release Renal baroreceptor Decreased renal perfusion pressure  increased renin release Catecholamines (sympathetic innervation) NA acts on B-receptors  v/c (by A1 adrenoceptors)  increased renin release NB: propranalol blocks renin release Catecholamines Macula densa Renal baroreceptors + ANP ADH + + – – Juxtaglomerular apparatus renin release + + Angiotensinogen K+ + + Aldosterone release Acts on Zona Glomerulosa In ADRENAL CORTEX Thirst – + Renin ATCH + Angiotensin I ACE ACE is localised to epithelium in LUNGS Angiotensin II + Sympathoexcitation Excites neurones to lesser stumuli + Vasoconstriction Proximal Na+ uptake ADH (Vasopressin) Produced by the posterior pituitary Release is dependent on Baroreceptors – drop in BP  increase ADH to maintain volume & BP Renal 15 Osmoreceptors – increased [ECF]  increase ADH  retain H2O  dilution Effects Decreases renin release (auto-regulation of system) Splanchnic vasoconstriction (increases BP – vasopressin used as Rx for life threatening hypotension, septic shock & bleeding oesophageal varices Reduced vasa recta blood flow  slows flow  less solute washout Increases distal tubule & collecting duct H2O permeability Increases medullary collecting duct urea permeability Renal 16 Acid base balance  Give an account of the renal handling of H+ and HCO3- as they relate to acid-base balance. HCO3- Plasma HCO3- = 24mmol / l Freely filtered Luminal surface is impermeable to HCO3Most reabsorbed in the proximal tubule (in the form of CO2 + H2O) Reabsorption is driven by the secretion of H+ ions by the Na+/H+ antiport Because all the H+ secreted is reabsorbed acidification happens elsewhere H+ Is cycled in the proximal tubule (to drive the reabsorption of HCO3-) Is actively secreted in the distal tubule / cortical collecting duct Produced in the cells from CO2 & H2O by carbonic anhydrase The HCO3- diffuses into the peritubular fluid, the H+ is actively pumped into the lumen Here it is free to diffuse back into the cells but is buffered by HPO42-  H2PO4(the HPO42- ions are available immediately as they are freely filtered) If there is long term acidosis (>3-7 days) … Peritubular fluid Proteins & enzymes are synthesized  glutamine (AA) is converted 2HCO33Na+ to NH3 & Glucose The NH3 can diffuse freely out of the cell 2HCO3H+ ions are secreted by a Na+/H+ 2K+ 2H2CO3 antiport in the proximal tubule & 2H+ by a proton pump in the distal Glucose tubule Glutamine The NH3 buffers the H+ ions  NH4+ Distal Proximal & these are trapped in the Na+ NH3 lumen due to their charge Normal urine has no ammonium so ammonium ions are a marker of NH4+ H+ H+ long-term acidosis Lumen The process also produces HCO3- to buffer the H+ ion excess in the blood H+ & K+ in the late distal tubule / Cortical collecting duct As the intercalated cells have a K+/H+/ATPase which pumps H+ out & takes K+ in a prolonged acidosis has consequence for K+ Excess H+  increased K+ reabsorption  low urine / high plasma K+ Can  cardiac complications (excitation)  Explain the metabolic and respiratory patterns of acid-base imbalance and describe their compensation. Normal values [HCO3-] = 24mmol/l [H+] = 40nmol/l pCO2 = 40mmHg pH = 7.4 (7.35-7.45) Respiratory acidosis (e.g. hypoventilation / COPD) Rise in CO2  rise in H+ = acidosis Compensation is metabolic (by HCO3-) As normally filtered bicarb is all reabsorbed kidney must excrete more H+ Metabolic acidosis (e.g. DKA / Exercise) Decrease in HCO3-  less buffering  acidosis Compensation is respiratory by hyperventilation & by H+ secretion from kidney Hyperventilation cannot be maintained long term  Rx required Mixed acidosis e.g. heart stops, no O2 in, no CO2 out Renal 17 Respiratory alkalosis (e.g. hyperventilation) Decrease in CO2  decrease in H+ = alkalosis Compensation is metabolic Increase excretion of HCO3- (requires loss of Na+ & therefore H2O) Metabolic alkalosis (e.g. vomiting) Increase in HCO3- (relative to H+ lost in vomit) = alkalosis Compensation is respiratory by hypoventilation Mixed alkalosis e.g. vomiting and hyperventiation PCO2 (mmHg) CO2 changes are respiratory Resp Acidosis PH 7.4 Increase = acidosis Decrease = alkalosis Compensation 40 Metabolic Acidosis Mixed Cause HCO3- changes are metabolic Metabolic Alkalosis Mixed Cause Increase = alkalosis Decrease = acidosis Compensation Takes the point back towards the line Compensation In general acidotic shifts are more life threatening than alkalotic ones Resp Alkalosis [HCO3-] mmol / l 24 Renal 18 Diuretics.  Give an account of the renal actions of: o Osmotic diuretics (e.g. mannitol, glucose) Freely filtered & stays in luminal fluid (non/minimal uptake) Holds water in the luminal fluid Solutes are reabsorbed as normal  more concentrated peritubular fluid  more dilute luminal fluid  concentration gradient for solute  some returns by diffusion  Net result is reduced solute reabsorption Mannitol – increases [blood] to draw fluid from CSF Glucose – if [glucose] > Tm glucose stays in filtrate  glycosuria + polyuria + thirst Non K+ sparing o Loop diuretics (e.g. frusemide) Act on the thick ascending limb Very potent & short acting (frusemide used to clear fluid from lungs in CCF) Inhibit Na+/2Cl-/K+ pump  decrease concentration of fluid at tip from 1200 to 500 mosmol / kg  decrease H2O reabsorption & increase urine production Non K+ sparing o Thiazides (act on early distal tubule) Cheap & widely used Block Na+/Cl- cotransport in early distal tubule Also act as vasodilators systemically  lower BP Non K+ sparing o Aldosterone receptor antagonists and amiloride (act on late distal tubule & CCD)  K+ loss due to Na+/K+ pump in distal tubule BUT not all Na+ reabsorbed  low Na+  H2O loss Aldosterone antagonists Peritubular fluid 3Na+ HCO3- Cl- Cl- 2K+ HCO3- CA H2CO3 CO2 + H2O H+ Very expensive  Reduces the number of Na+/K+/ATPase pumps  Reduces the permeability of luminal surface to K+  Decreases K+ secretion & Na+ reabsorption NB: will have no effect on a patient who has no aldosterone! K+ Intercalated cell Principle cell NB: These are K+ sparing amiloride Na+ Lumen K+ Amiloride H+ Proton Pump  Blocks Na+ reabsorption  Decreases K+ secretion o Carbonic anhydrase inhibitors  Block CA on luminal surface  prevent HCO3- reabsorption  As H+ cannot cycle (in Na+/H+/ATPase) Na+ is left in lumen  alkaline urine (HCO3- excretion) & metabolic acidaemia o Vasopressin Antagonists (still in development) Would prevent any water reabsorption  120ml/min urine produced Act on V2 receptors to mobilise H2O without interfering with solutes Renal 19 Disorders of fluid and electrolyte balance. Osmolarity (estimated) = 2 (Na+) + 2 (K+) + Glucose + Urea NB: if lab osmolarity > estimated then consider alcohol, ethylene glycol or other additives  Describe the factors influencing plasma Na + and K+ concentrations. NB: thirst is stimulated by osmolarity (usually > 280ml) so dehydrated with low osmolarity wont be thirsty until… Thirst is overridden by low BP  RAA system activation  Na+ & H2O retention & some increase in osmolarity  thirst & ADH secretion (water retention) drink This is VERY DANGEROUS as the water intake will reduce osmolarity further Na+ balance Intake is variable with a western diet – 100-200mmol/day on average Loss = sweat, faeces and through kidney Hypernatraemia ALWAYS assess the water status (dehydrated V oedematous) Dehydrated Reduced fluid intake – not available, coma, dysphagia, loss of thirst mechanism (head injury, meningitis, sarcoid) Loss of water (H2O with low Na+ content) – GI (vomit, diarrhoea, fistula), skin (sweating, burns), Lungs (hyperventilation / ventilated on dry air / tracheostomy), Urine (DM, DI) Oedematous Excess intake – dietary, psychogenic Sodium retention – Conns syndrome (primary hyperaldosteronism)  High (N) Na+ & water retention (to dilute Na+) with low K+ and low H+ (= high bicarb) = metabolic alkalosis Hyponatraemia With volume overload Increased fluid intake - often iatrogenic Water retention – renal failure, SIADH (excess ADH  water retention, volume expansion and dilutional hyponatraemia  high BP  RAA turns off  loss of Na+ - see more in endocrine notes) Fluid redistribution – liver failure, cardiac failure, myxoedema in hypothyroid With volume depletion Replacement of Na+ rich fluid with Na+ poor – DM, diuretics, D&V Primary Na+ loss – adrenal insufficiency = Addisons (low costisol and hypoaldosteronism ( low Na+, High K+, H+ retention = metabolic acidosis) With normal blood volume Shift of water / Na+ - ethanol intoxication, mannitol, sick cell synd Artefact of lab test – hyperproteinaemia / hypercholesterolaemia  Na+ displaced in sample K+ balance Intake = excretion Intake = 100mmol/day Excretion = 90-95 mmol/day urine, 5-10mmol/day stool, <5mmol/day sweat Hypokalaemia [K+]  hyperpolarizes membrane  less excitable But removes normal inactivation of Na+ channels   membrane excitability Causes of Hypokalaemia  Decreased net intake (unusual as found in meat, fruit & veg)  Increased entry to cells (transient) Renal 20 o o o Alkalosis Insulin (diabetic hyperglycaemia f.b. insulin, K+ already low) B2-adrenoceptor activation (adrenaline, stress, hypoglycaemia, inhalers) o Familial periodic paralysis – Na+/K+/ATPase very sensitive to insulin  rapid drop in K+ after large load of carbohydrate ingestion  Increased GI losses (diarrhoea & vomiting) o Vomiting  dehydration  RAA system  Na+ retention & K+ loss Give 1l NS over 2-4 hrs (will dilute K+ slightly further) fto correct the K+ loss then give NS + K or K+ infusion to correct K+  Increased urinary losses o Loop / thiazide (non K sparing) diuretics o Mineralocorticoid excess (corticoid acts on aldosterone receptor o Vomiting  Increased sweat loss  Hypomagnesaemia – cofactor for Na+/K+/ATPase Consequences of hypokalaemia  ACG changes (inverted / flattened T waves) and Cardiac arrhythmias (ischaemia, esp with digitalis)  Muscle weakness / paralysis (inc gut)  Rhabdomyolosis (? Hypoperfusion)  Renal dysfunction o Polyuria, polydipsia ( ADH effect,  medullary gradient) o Increased NH3/NH4+ (intracellular acidosis due to K+/H+ exchange) o Increased HCO3- reabsorption Treatment of hypokalaemia KCL & KHCO3 (K+ citrate) oral/IV Hyperkalaemia [K+]  depolarises membranes  more excitable But persistent depolarisation inativates Na+ channels   excitability  impaired cardiac conduction / muscle weakness (paralysis) Causes of hyperkalaemia  Increased intake (salt substitutes / IV)  Movement from cells into ECF o Pseudohyperkalaemia o Metabolic (mineral acidosis) = loss of HCO3o Insulin deficiency & hyperosmolality (uncontrolled DM) o Tissue catabolism o B2-adrenoceptor antagonism o Severe exercise (rhabdomyolyisis) o Haemolysis  Decreased urinary excretion o Renal failure ( distal tubular flow) o Hypovolaemia ( distal tubular flow) o Hypoaldosteronism (RAS, Adrenal synthesis etc e.g. addisons) o K+ sparing diuretic (e.g. spironolactone) + ACEi ( K+ retention) Consequences of hyperkalaemia  Muscle weakness/paralysis (sustained depolarisation inactivates Na+   excitability)  ECG changes (peaked T waves) and Cardiac arrhythmias Treatment of hyperkalaemia  Antagonism of membrane actions o Ca2+ gluconate 10mls (restores membrane activity to normal = cardioprotective) o Hypertonic saline (Na+ if hyponatraemic)  Increase K+ entry to cells o Insulin + glucose Renal 21 o NaHCO3 (alkalosis  K+ into cells & treats any acidaemia) o B2-adrenoceptor agonists (albuterol / salbutamol) o Hypertonic saline (Na+ if hyponatraemic) Removal of excess K+ o Diuretics o Cation-exchange resin (Na as oral / enema) o Haemodialysis / peritoneal dialysis  B-Cell Pancreas Skeletal muscle + + K distribution normally due to Na+/K+/ATPase + Insulin Na+ 2K+  transient drop in extracellular K+ Insulin Receptor H+  Na+ 3Na+ + + + Insulin & B2 agonists stimulate Na+/K+/ATPase cAMP ATP + 3Na+ B2-adrenoceptor Glucose 2K+ B2 agonist e.g. salbutamol Liver Gluconeogenesis Hyperlipaemia / hyperproteinaemia The more protein / lipid in the blood, the less plasma per unit volume  apparent low [Na+] & [K+] but osmolality normal Haemolysis Releases high concentration K+ from inside cells  hyperkalaemia Renal 22 Renal Failure  Appreciate the signs and symptoms of renal failure. “Renal Failure” = Failure of renal excretion due to decreased GFR May be accompanied by decreased EPO, Ca absorption, loss of acid-base & BP regulation  Classify renal failure into pre-renal, renal and post-renal causes and outline the pathology of the common diseases that may cause each type. o o o  Pre-renal  reduced perfusion = reduced filtration  Oliguria / anuria  Hypovolaemic shock  Cardiogenic shock  Septicaemic shock  Renal artery stenosis Renal  Glomerulonephritis  Chronic pyelonephritis  Interstitial nephritis  Diabetic nephropathy  Hypertension  Vasculitis. Post-renal  Benign prostatic hyperplasia  Prostate carcinoma  Renal stone disease  Retroperitoneal fibrosis  Other causes of ureteric obstruction Describe the 2 syndromes of partial renal failure Nephritic syndrome Disturbance of glomerular structure involving reactive cellular proliferation  Oliguria (due to decreased renal blood flow)  Haematuria (due to leakage of red cells from damaged glomeruli  Uraemia (retention of waste products due to poor filtration)  Low flow  activates RAA system  fluid retention & mild hypertension Nephrotic syndrome Abnormality of the glomerular basement membrane  capacity for selective retention of proteins  Proteinuria (mainly albumin)  hypoalbuminaemia  oedema  Low immunoglobulins  susceptibility to infections  Increased fibrinogen  susceptibility to thrombosis  Reduced levels of serum apoproteins  hyperlipidaemia Renal 23 Acute Renal Failure / Dysfunction (ARF / ARD) “Acute renal dysfunction” = abrupt deterioration in function, reversible if caught early enough Sudden cessation of the majority of nephrons Usually associated with tubular necrosis Metabolic compensation absent NB: eGFR is calculated from creatinine using the patient’s age and gender (and should be recalculated if the patient is black) IT IS ONLY VALID IN CHRONIC DISEASE STATES - It should NOT be used in children, pregnancy or in acute renal failure It should NOT be used for adjusting drug doses  Describe the clinical features of ARF o Anuria (or oliguria < 400ml / day = < 0.5 / kg / hr) – due to decreased renal flow o Vomiting o Ion & acid base imbalance  Increased K – due to tubular damage  Metabolic acidosis – due to inability to secrete H+ o Hypertension & Fluid overload – due to High Na+ because decreased GFR o Increasing urea & creatinine (urea rises first) NB: creatinine is produced at approx 150-200mmol / day. Time since total renal failure can therefore be calculated  Common causes Prerenal – haemorrhage, fluid loss (GI tract, urine, shock), cardiogenic (MI), sepsis Renal artery stenosis + ACEi - if low flow then kidney relies on high BP (from activation of RAA) to ensure sufficient filtration pressure. If started on ACEi for BP  suppression of angiotensin (responsible for efferent arteriole contraction)  drop in filration pressure  ARF. ALWAYS check U&Es before and 1 week after starting ACEi. Also advise patient to omit ACEi if severe N&V Renal – Acute tubular necrosis (due to toxins or ischaemic damage) – the tubules are dead and the patient should be supported until some function recovers / until transplant available. Often caused by prolongation of pre-renal causes Glomerulonephritis (assoc with fever, rash and Look for rash, fever, malaise, joint raised WCC) problems, blood / protein in urine Interstitial nephritis (most commonly due to Should be treated aggressively to penicillins/NSAIDs, SLE, lymphoma etc) Vascular (cholesterol emboli, HUS, preserve renal function Preeclampsia, DIC) Post renal – obstruction of outflow (stones, prostate, tumour), PUJ in children, strictures if h/o instrumentation  Discuss the associated electrolyte abnormalities including hyperkalaemia and describe the management of life threatening hyperkalaemia. (see also earlier in notes) Hyperkalaemia > 6.0 can  ECG changes (wide QRS, long PR, peaked T & near sinusoidal pattern = approx 5 mins to arrest!) Management ECG monitoring Ca2+ gluconate 10mls of 10% over 5 mins (cardioprotective – reduces myocardial excitability) IV Dextrose and insulin 10U actrapid / 50mls 50% dextrose (insulin drives K+ back into cells). Peak effect within an hour, lasts 1-2 hours Renal 24 Salbutamol nebuliser 5mg (alternative use is IV). Peak 90 minutes, lasts upto 6 hours Sodium bicarbonate – will correct acidosis and lower K+ BUT high Na+ content so avoid if fluid overloaded BEWARE REBOUND (once insulin decreases  K+ comes back out of cells so careful monitoring vital Other problems Anuria / Oliguria  fluid overload  pulmonary oedema Also  acidosis  Outline the investigation of a patient with acute renal failure including urinalysis, laboratory and radiological tests. This should include an appreciation of the importance of historical data (if available) on renal function in the determination of acute rather than chronic renal failure. BP – & JVP - fluid overload Urine dipstick – for protein, glucose, WCC, blood etc Urine microscopy – RBC casts (glomerulonephritis), granular casts (acute tubular necrosis), WCC casts (Interstitial nephritis) Urine Culture – send urgent as takes days to come back USS – for obstruction of outflow. If present then relieve immediately.  IVU Bloods – FBC (low Hb = long term problem / major blood loss) Clotting U&E, Creatinine, Ca & Phosphate ABG – for acidosis and often low bicarb. Also gives immediate K+ CXR – to assess for pulmonary oedema Consider – autoimmune screen for wegners, lupus, goodpastures, myeloma screen History Drug history is essential. Stop any non essentials esp: ACEi’s, angiotensin blockers, K-sparing diuretics, metformin (contraindicated if raised creatinine) Contact GP to obtain any previous measures of renal function  Outline the principles of treatment including the importance of fluid balance, correction of electrolyte disturbance and acidosis and treating hypertension. Pulmonary oedema High flow O2 IV nitrates IV opiates (beware accumulation and respiratory depression) IV diuretics (vasodilators, diuresis if residual function) Electrolyte disturbance Check U&Es then slowly correct electrolytes  Outline the indications for dialysis. Severe hyperkalaemia (> 6.5 or with ECG changes) Intractable fluid overload – not responding to diuretics Metabolic acidosis – pH < 7.2 Uraemia – with clinical Sx (pericarditis, encephalopathy) Renal 25 Chronic Renal Failure (CRF) “Chronic renal failure” = long standing, progressive deterioration, usually not reversible Caused by incremental loss of nephrons over extended period of months/yrs Renal function slowly declines Progressive increase in nitrogen retention Urea/creatinine due to progressive tubular failure Affects 10% of the population. 1% progress to renal replacement therapy Normal aging  loss of 1ml / min / yr of GFR (once over 40) “progressive disease” = > 3ml / min / year loss of function  refer to renal team  Describe the classification of CKD Stage 1: > 90 ml/min with another abnormality (NB: > 90 = normal so other abnormality = blood / protein in urine, or structural problem e.g. scarring, polycystic) Stage 2: 60-89 ml / min with another abnormality (NB: 60-90 would be normal for an elderly person) Stage 3: 30-59 ml / min Stage 4: 15-29 ml / min Stage 5: <15 ml / min  Describe the signs, symptoms & clinical features associated with chronic renal failure History NB: many patients will have no Sx in the early stages.  Short stature (if CRF from childhood)  Duration (deterioration)  Drug ingestion – esp NSAIDs, other analgesia & herbal remedies  Medical & surgical Hx – esp chemotherapy and SLE  FH of renal disease  Compare previous tests if available Early – often initially asymptomatic, Sx start when urea > 40mmol/l  Malaise & lethargy  Decreased appetite Sx that occur are due to :  Insomnia Uraemia  Nocturia & polyuria (impaired concentrating ability) Anaemia  Itch Acidosis  Nausea, vomiting & diarrhoea Fluid overload  Paraesthesia & tetany (low Ca2+) CaPO4 imbalance  Restless legs Later  Impotence & amennorhoea  Dyspnoea – due to oedema & anaemia (low EPO)  Oedema – peripheral & pulmonary due to fluid retention  Confusion, mental slowing & clouded conc (urea > 50mmol/l)  Seizures & myoclonic twitches  Coma NB: UREMIA – Not just raised serum urea. O/E It’s a clinical syndrome of metabolic and  Pallor (anaemia) endocrine abnormalities incident to  Increased photosensitive pigment in severe chronic renal damage skin ( healthy look!)  Brown discolouration in nails  Scratch marks from itch  Signs of fluid overload – oedema, effusions, pericardial rub Renal 26       Cardiac murmurs – mitral regurg (calcification), aortic & pulmonary regurg (vol overload) Hypertension Glove & stocking neuropathy (rare) SHOULD – do rectal & vagina examination ALWAYS – assess JVP, skin turgor, BP (stood & laid) & peripheral circulation List and outline the pathology of the common causes of chronic renal failure NB: 23% of cases never have a cause found o Diabetes (18%) Due to glomerular damage, vascular disease and increased risk of infections o Glomerulonephritis (10%) Diffuse global disease of glomeruli often due to trapping of immune complexes, can be triggered by infection. Endothelial cells proliferate, polymorphs gather in the capillaries and immune complexes clog the vessels o Macrovascular disease (7.5%) Renal artery stenosis  ischaemia and reduction in nephron function  end stage shrunken kidney with contralateral kidney hypertrophy. Ischaemic kidney  activation of RAA system  fluid retention  hypertension  damage to other kidney o Hypertension (5%) Benign HT  Changes to muscular artery walls  reduced flow. Glomerular walls become hyaline lined. Reduced blood flow  ischaemic damage Malignant HT  necrosis of arteriole walls (fibrinoid necrosis) & glomerular tuft necrosis o Polycystic kidney disease (5%) Cysts  compression of renal parenchyma  impaired function o Pyelonephritis (7%) Acute suppurative bacterial infection of kidney and renal pelvis associated with UTI Causative organisms - 85% normal commensals of gut. E Coli then Proteus, Klebsiella, Enterobacter, Strep fecalis, Staphylococci (in bacteraemia septicaemia), Non enteric bacteria usually introduced as hospital infection, following instrumentation, or septicaemia Pathology - Patchy suppurative inflam/tubular necrosis, Focal abscesses, Wedge like areas of suppuration Risk factors / associations - Urinary obstruction, History of intrumentation/ catheterisation, Vesicoureteric reflux, Pregnant, Female, Preexisting renal lesions (scarring), Diabetes Clinical features - Pain costo-vertabral angle, Fever, malaise, dysuria, frequency, Urgency, Pyuria, Ix - Tubule generated white cell casts indicate presence of renal involvement as apposed to having only cystitis o Obstructive uropathy Obstruction to urine drainage (calculus, prostate etc)  dilatation of pelvis = hydronephrosis. High fluid pressure in pelvis  intrarenal reabsorption of fluid  atrophy of renal tubules, glomerular hyalinazation & fibrosis. o Interstitial nephritis Inflammation in the interstitium assoc with tubular atrophy. Has many causes: Drug induced acute – 2-3 weeks post exposure. Recovers on withdrawal Drug induced chronic -  CRF due to permanent damage Analgesic – due to NSAIDs. Higher risk of urothelial CA Renal 27 Radiation – after treatment for malignancy  Discuss the effect of chronic renal failure on blood (anaemia of chronic disease) and bone (renal bone disease) based on disturbance of normal renal function. Early Tubules fail to concentrate urine Polyuria – with low Na+ because flushed out  dehydration Compensated metabolic acidosis  low serum bicarb & compensatory hyperventilation (kussmall resp) Hyperkalemia End Stage Decreased filtration  RAA system activated  Na retention  H2O retention  volume overload  HT  CCF & pulmonary oedema Anaemia – normochromic and normocytic – due to reduced EPO May be worsened by ulcer, GI or urinary loss Extreme electrolyte imbalances can  haemolysis Cardiovascular complications CCF & HT  fibrinous pericarditis Respiratory complications Pleuritis, effusions & pulmonary oedema Skeletal complications Renal osteodystrophy High phosphate, low Ca2+ due to low Vit D PTH  increased osteoclasts  reabsorption of bone  cysts in bone  cysts fill with blood  “osteitis fibrosa cystica” (esp in phalanges) = “brown tumour”  osteoporosis (renal rickets in children)  Discuss the investigation of a patient with chronic renal failure. Urinalysis Haematuria Proteinuria Glomerulonephritis Infection / glomerular disease > 0.5g protein in 24hrs is abnormal CRF / diabetes Glycosria Urine microscopy WBCs Infection Eosinophils Allergic nephritis / cholesterol embolisation Granular casts Active renal disease Red cells (casts) Glomerulonephritis Urine biochemistry 24hr creatinine clearance Measure of renal function Low osmolality Renal disease (inability to concentrate) PTH To assess levels to avoid osteodystrophy Serum biochemistry Urea & creatinine Increased creatinine kinase Rhabdomyolysis Haematology FBC if anaemic give EPO Eosinophilia vasculitis / nephritis / cholesterol embolus ESR (if increased viscosity) myeloma / vasculitis Thrombocytopenia intravascular haemolysis Immunology SLE, glomerulonephritis, scleroderma, goodpastures syndrome, TB, Hep B&C, Malaria Radiology US to check renal size to exclude hydronephrosis Renal 28 (suspect RAS if > 1.5cm size difference between) XR / CT for calcinosis / stones Biopsy If unexplained renal failure with normal sized kidneys  Outline the treatment options and discuss the indications for renal dialysis. Slow progression Control BP (< 130/80 or < 125/75 if proteinuria) Reduce proteinuria – ACEi or angiotensin receptor blockers are protective (providing no renal artery stenosis – check bloods before & 1 weeks after any dose change). Work by reducing filtration pressure  some drop in GFR (20% acceptable)  slows progression Optimise DM control, lipid levels, smoking, diet etc Treat complications Hyperkalaemia Anaemia - Give EPO – avoid transfusion as high fluid vol, high in K+ and introduces antibodies which can decrease chance of successful transplant Renal bone disease & hyperparathyroidism – phosphate binders, vit D, dietitician CVS disease – use statins to bring cholesterol < 5mmol/l Give Vaccines – flu jab yearly, pneumococcus 5 yrly, Hep B course Optimise & educate patient for end stage Weight loss Smoking cessation Avoid NSAIDs & nephrotoxics (gentamicin) Adjust drug doses for those with renal excretion Educate as to progression of disease Dietary advice based on U&E pattern Prepare for renal replacement therapy  Outline the different forms of renal replacement therapy o Haemodialysis (12%) 4 hrs 3x weekly, hospital based Try to ensure fistula is in place 4 months before it is required (incase rapid decline in function as much greater complication rate if having to give HD via central line Complications include stress on CVS system due to large fluid build up between sessions  loss of elastic properties of vessels and high Ca2+ levels  calcification of vessels  poor compliance. Can get “steal” syndrome – where body distal to fistula is rendered ischaemic due to blood being diverted  must tie off fistula or lose limb o CAPD (continuous ambulatory peritoneal dialysis) 40% Catheter in peritoneum. Home based. Higher technique failure than HD Complications include peritonitis and membrane failure (scarring etc) o Transplantation (45%) The transplanted kidney is sited in the iliac fossa where it is firmly supported & where only short lengths of renal vessels & ureters are needed to connect it. The renal AA & VV are joined to the external iliac AA & VV. The ureter is sutured to the bladder Only listed for Tx if minimum prognosis of 5 yrs & medically fit. Need diagnosis and to know that new kidney will not be affected by disease 95% 1 yr graft survival, 60% at 10 yrs, 20-40% at 20yrs Renal 29 Best prognosis it transplant obtained ASAP as PD is no very efficient and HD  damage to vasculature (see above) Need extensive follow-up o Palliative care Some patients prefer to die than undergo dialysis Life expectancy is approx 1 year once end stage is reached Renal 30 Nephrotic Syndrome  Define the nephrotic syndrome. High protein in urine (>3g in 24hrs) Low in serum (albumin < 30g/L)  oedema (due to decreased protein) – shows as weight gain, HT, anorexia Patients often also have high serum cholesterol Due to damage to BM of glomerulus (e.g. DM, lupus, myeloma & glomerulonephritis)  List the three main primary renal causes and outline briefly their key pathological features o Minimal change nephropathy, Mainly children under 6 (10-15% in adults) T-Lymphocyte mediated. Small proteins lost = albumin Ix -. Biopsy unless clear cause – sample will be normal = minimal change Rx with Steroids o Membranous glomerulonephritis 20-30% in adults (2-5% in children) Biopsy shows diffuse thickened BM Immunofluorescence shows IgG and C3 deposits CRF supervenes in 50% of cases o Proliferative glomerulonephritis Histological classification (focal, diffuse or mesangiocapillary) Common due to strep sore throat / skin Strep antigens deposited on glomeruli  reaction Biopsy shows inflammatory reaction affecting mesangial and endothelial cells Immunofluorescence shows IgG and C3 deposits  List secondary causes such as … o Diabetes o Amyloid disease o SLE o Drugs o Allergies  Outline the investigation necessary to confirm the diagnosis. Urinalysis to confirm proteinuria Serum cholesterol & protein, FBC, U&E, LFT, ESR, CRP, immunoglobulins, complement levels, autoantibodies Urine microscopy (may show fat globules) Renal biopsy to establish type & likely cause  begin treatment  Outline the treatment including the need for diuretics and a low-salt diet. Monitor U&E, BP, Fluid balance & weight regularly Identify and treat the underlying disease Salt intake restriction (protein doesn’t need restricting) Diuretics e.g. frusemide with U&E monitoring. Aim to loose 1Kg / day Treat infections promptly, vaccinate Prophylactic heparin if immobile Treat hypertension Renal 31 Glomerulonephritis “Glomerulonephritis” - Primary or secondary immune-mediated disease characterized by inflammation of the glomeruli– may be temporary & reversible  Outline the main pathological processes affecting the glomerulus including primary disease and those relating to systemic disease particularly the vasculitic illnesses. Primary causes are one which are intrinsic to the kidney Secondary causes are associated with certain infections (bacterial, viral or parasitic pathogens), drugs, systemic disorders (SLE, vasculitis) or cancers.  Describe the clinical presentation of glomerulonephritis. Haematuria (micro/macroscopic) Proteinuria Hypertension Oedema Temporary oliguria and uraemia Urine appears foamy & bloodstained  Outline the investigation necessary to confirm the diagnosis. Standard Bloods – FBC, U&E, LFT, ESR, CRP Special bloods – immunoglobulins, electrophoresis, complement levels, autoantibodies, ANA, ANCA, Anti-dsDNA, anti-GBM, blood culture, HBSAg, Urine – RBC, Casts, MC&S, Bence-Jones proteins Others – CXR, renal ultrasound, renal biopsy  Outline the treatment options including the role of immunosuppressive therapy for some forms of GN. General management Refer to nephrologist Keep BP < 130/80 (<125/75 if proteinuria) Give an ACEi (prevents / slows progression to full renal failure Treat any obvious underlying cause / contributive factors Specific management Steroids in many cases will  improvement Other anti-immune measure such as azothioprine, cyclophosphamide, and anti Ig drugs can be helpful Renal 32 Obstructive Conditions of The Kidney And Ureter  Describe the causes, symptoms and signs of acute and chronic ureteric obstruction and discuss their management. Causes Obstruction in lumen  Calculus – most commonly in renal pelvis, where it crosses iliac at pelvic brim or on entering the bladder  Blood clot  Sloughed papilla (due to DM, analgesia abuse or sickle cell)  Tumour of renal pelvis / ureter  Bladder tumour Obstruction in wall  Ureteric stricture (TB, post calculus removal)  Ureterovesical stricture (congenital, uterocele, calculus, schistosomiasis)  Congenital neuromuscular dysfunction  Congenital megaureter  Congenital bladder neck obstruction  Neuropathic bladder  Congenital urethral valve  Urethral stricture (calculus, gonococcus, post instrumentation)  Pin hole meatus Obstruction due to external pressure  Tumours (retroperitoneal, colon, cervix etc)  Diverticulitis  Aortic aneurysm  Retroperitoneal fibrosis  Ligation (iatrogenic)  Retrocaval ureter (on RHS)  Prostatic enlargement  Phimosis Pathophysiology Increased intraluminal pressure  dilatation proximal to obstruction  compression & thinning of renal parenchyma  thin rim & reduced functioning nephrons Clinical features Upper tract obstruction  Loin pain – worsens with increased urine output (e.g. high fluid / alcohol intake)  Anuria – if both kidneys affected  Polyuria – if partial obstruction as body attempts to flush it out  Malaise, fever, septicaemia if infection Bladder outflow obstruction  Hesitancy with decreased force of stream  Terminal dribbling & incomplete emptying  Increased frequency with decreased volume  overflow incontinence  Infection  frequency, urgency, urge incontinence, dysuria, cloudy & smelly urine Common signs  Tenderness  Palpable kidney (hydronephrotic)  Enlarged bladder Management o Relieve obstruction (by nephrostomy if necessary) o Find & remove cause o Prevent / treat infection Renal 33 Urinary Calculi  Discuss the aetiology and presentation of calculi in the kidney, ureter & bladder 2% incidence at any given time (M:F = 2:1) > 50% will have recurrence within 10 yrs Presentation Calyx stones Often asymptomatic / dull loin pain Pelvic stones Renal colic Haematuria (very rare to have stone disease without haematuria) Can be infection Ureteric stones Most excruciating (loin to groin, background pain + crescendos of sharp pain + restlessness, worsens with increased fluid intake & output) Vomiting & bowel distension – due to extravasation of urine to retroperitoneum (mimics intestinal obstruction) Tenderness over loin & iliac fossa Haematuria Bladder stones Outflow obstruction symptoms Usually WITHOUT pain & haematuria Occasionally pain refers to tip of penis, worse with exercise, improves on lying down Risk factors Inadequate drainage of urine - uterocele, diverticulum, hydronephrosis or chronically obstructed bladder, hydronephrosis Excess of normal constituents – Dehydration, increased Ca2+ excretion (hypercalcaemia in hyperparathyroidism, prolonged immobilisation or malignancy), increased uric acid excretion (following gout & chemotherapy), increased oxalate excretion (due to excess intake, primary oxaluria (inherited liver enzyme def) or secondary oxaluria (resection or disease of terminal ileum) Presence of abnormal constituent - UTI – proteus mirabilis (due to making urine alkaline), foreign body (stent, suture), vitamin A deficiency (causes hyperkeratosis of epithelium  slough), cystinuria (metabolic error) Types of stone Supersaturation stones Cystine (1%) – in cystinuria (AR), precipitated by penicillamines Uric acid (5%)– hard, brown, smooth. Radio-lucent. Linked with gout (overproduction), post chemotherapy (rapid protein catabolism), dehydation (inc UC & ileostomy patients). Precipitated by increased acidity. Rx – large water input + bicarbonate to keep urine alkaline. Allopurinol can prevent formation of uric acid Calcium stones (majority of non-infective stones) Calcium oxalate (60%) – hard, sharp, spikey, brown/black (due to blood) Calcium phosphate (33%) – (Ca, Ammonium & Mg = triple stones), hard white chalky, found with infection, majority of staghorn calculi Renal 34 Are due to… Primary (hepatic) oxaluria – excess oxalate produced due to genetic enzyme defect. Eventually  renal failure. Transplated kidney will have same problem, liver & kidney transplant will be successful. Secondary (ileal) oxaluria – occurs in diseases of terminal ileum where bile acids are absorbed. Lack of bile  fat left in gut  insoluble fat/calcium compound  excess of oxalate in blood  excreted in urine  stone. Rx – cholestyramine (binds oxalate in gut) and avoid oxalate rich foods (tea, coffee, chocolate, spinach, rhubarb) Hypercalciuria – mainly in men (>350mg/24hrs men / >300 women). 3 types = Renal – decreased renal reabsorption. No Rx Absorptive – too much calcium absorbed from bowel. Rx – drink lots Resorptive – excess absorbed from bone (depends on parathyroid – see box below) Parathyroid hormone [Ca x PO4] is always constant – so if Ca  then PO4 must  Parathyroid hormone is released in response to low Ca Encourages osteoclasts to dissolve bone & release Ca into blood Primary hyperparathyroidism For no reason PTH increases  [Ca] rises & [PO4] falls Excess Ca2+ enters urine  precipitates in renal tract  mephrocalcinosis or stone in renal tract Usually diagnosed incidentally by raised Ca or during stone investigation Rarely detected as osteitis fibrosa cystica (cystic cavities of osteoclasts in bone) Ix – repeat Ca level. If still raised  radioimmunoassay for PTH Rx – can be due to adenoma of gland / hyperplasia of all 4. Surgically remove Secondary hyperparathyroidism In chronic renal failure PO4 is not adequately excreted  Ca has to fall  precipitated to soft tissues ( joint stiffness & deafness) because Ca is low, PTH is released (glands become hyperplastic) Commonly seen in patients undergoing dialysis Can be prevented by large doses of Vit D to increase absorption from bowel Tertiary hyperparathyroidism Follows secondary hyperparathyroidism Despite vit D glands continue to produce more PTH than needed to keep constant Ca Rx – remove glands Investigations Oxalate stones are radio-opaque; Uric acid & cystine stones are not; Dipstick urine – stones very rarely present without blood in urine Can send urine for uric acid estimation to check for gout MSU for culture – will show if infection present Bloods – FBC, U&E. Check [Ca] to exclude hyperparathyroidism KUB – will show 90% of stones, not needed if also having IVU US – will show a shadow from the stones but very operator dependent IVU – will show any oxalate stones of control (KUB) film, hydronephrosis & filing defects on contrast films. Will also show if urine is stagnating in system Stone analysis – once the stone is removed / passed it should be examined to assess the likely cause of its formation  Describe how renal stones are treated including some knowledge of non-operative methods of treatment. Renal 35 Extracorporeal shock-wave lithotripsy (ESWL) Use X-ray or ultrasound to localise the stone The fragments can  temporary obstruction (“steinstrasse”)  renal colic Also give large volumes of fluid & diclofenac for analgesia Double-J ureteric stent Inserted to enable the ureter to dilate after passage of stones after ESWL Can be left in for several months but can be a nucleus for stone formation so must be well monitored & removed within reasonable time Percutaneous nephrolithotomy A needle is inserted to the renal pelvis by US / XR guidance The passage is dilated up & instruments & camera passed The stone is then broken up and removed Ureteroscopy Passed up the ureter to remove small stones – can have instruments passed through it Choice of treatment is based on location of the stone Ureteric colic Analgesia – injected pethidine ( smooth muscle relaxation) / rectal diclofenac Stone in a calyx Rarely cause any problems, simply observe If causing pain  ESWL Stone in the renal pelvis Stones of <5mm should be able to be passed without physical intervention If > 5mm  ESWL / PCNL ideally before Sx begin Can be removed by pyelolithotomy (approached through 12 th rib incision) Staghorn stones Fill the entire pelvis & most calices, usually infection with proteus mirabilis Body of stone removed with PCNL with outliers by ESWL Stone in ureter If no infection  wit & wait as long as stone is progressing If the urine is infected there is a risk that obstruction with back-pressure will cause septicaemia and/or obstructive nephropathy  emergency percutaneous nephrostomy or pass double-J splint The infection is difficult to treat until the stone is removed & can cause the stone to grow If the stone is not making progress  ESWL / utereroscopy Stone in the bladder If small enough to travel down the ureter will usually be able to exit the bladder Outflow obstruction (e.g. prostate) may  stone trapping Can be removed by resectoscope, lithotripsy, swiss jack-hammer or Q-switched laser If very large a suprapubic lithotomy is safest Acute calculous anuria Due to blockage of both ureters by stones / obstruction of a solitary kidney Rx with percutaneous nephrostomy / retrograde ureteric stenting. If uraemic  haemo/peritoneal dialysis Prevention of recurrence Treat any identifiable cause In idiopathic stone-formers increase fluid to aim for 2-2.5l urine /day In idiopathic hypercalciuria advise high fluids + thiazide (can ppt DM, gout & worsen hypercholesterolaemia). Also reduce animal proteins & sodium intake In infective stones use low-dose prophylactic Abx, changing every 3 months In uric acid stones give allopurinol & bicarbonate (beware as can ppt calcium stones) In cystine stones drink 5l in 24 hrs with 2 x 500ml overnight, or use penicillamine (but many SE) Renal 36 Neoplastic Conditions of The Kidney And Ureter  Describe the clinical features, diagnosis and management of renal cell carcinoma, Wilm's tumour, transitional cell carcinoma and renal cysts. Wilms’ Tumour (embryoma) 10% of all childhood cancers, usually presents <5yrs. 1 in 13,000 children 1 in 10 wilms’ tumours are bilateral Very anaplastic Can be inherited or aquired Inherited is AD (loss on Chr 11) assoc with aniridia, hemihypertrophy, macroglossia, multicystic disease, neurofibromatosis & adult renal cell carcinoma One subgroup behaves benignly (mesoblastic nephroma) but must be completely excised Spreads by direct invasion to muscle & bowel, & via blood to lungs. Eventually erodes renal pelvis  haematuria = bad prognosis Presentation A large lump (noticed on bathing) in a wasted baby Pain Haematuria (late sign) Hypertension Fever &  red & white cell counts Weight loss, anorexia Investigation US fb CT (may require GA to keep baby still) ΔΔ = neuroblastoma – has speckled calcification & displaces kidney downward Staging Refer to a specialist centre, Often spreads to lung & liver Rx Usually radical surgery with wide excision margin & radiotherapy fu If too large chemotherapy can be used to induce regression before surgery 75-90% 5 year survival Renal cell carcinoma (Grawitz tumour, hypernephroma) 80% of all renal tumours. M:F = 2:1. Usually > 40 yrs, average = 55yrs Assoc with von Hippel-Lindau syndrome – angiomas in cerebellum & retina with cysts in liver & pancreas May be assoc with cadmium pollution & more commonly seen in those on dialysis (found by routine US scans) < 3 cm = adenomas, > 3cm = renal cell carcinoma but often met at < 2cm Staging – 1 = < 2.5cm, 2 = > 2.5cm, 3 = spread out of capsule / into veins, 3c = into cava Grading – based on mitosis Presentation Often incidentally on unrelated US while still asymptomatic Loin pain, loin mass & Haematuria – 50% means has eaten into collecting system painless haematuria = Loin pain / aching – 40%. Spread into surrounding tissues classical triad but only Loin mass – 25% – tumour is very large present in 15% Can present with neoplastic hormone syndromes Pyrogen – loss of weight, pyrexia, night sweats, raised ESR EPO – erythrocytosis without increase in platelets (5%) Marrow toxin – anaemia Renin – hypertension (30%) PTH – hypercalcaemia Stauffer’s factor – hepatosplenomegaly Glucagon – diarrhoea, enteropathy Tumour proteins – glomerulonephritis Amyloid – amyloid in contralateral kidney Renal 37 Unknown factor – paraneoplastic motorneurone disease Spreads via lymph to para-aortic nodes & blood stream along IVC  emboli Left sided varicocele if left renal vein is invaded (blocking drainage) Investigations Urine dip – almost always blood Bloods – raised ESR & abnormal liver biochemistry US shows echos (to differentiate cystic from solid mass) IVU & CT show mass distorting the collecting system MRI is most sensitive for looking at mets Bone scan – looking for metastatic disease (raised Ca / Alk phos) Management Small tumours – removed by partial nephrectomy Large tumours – radical nephrectomy (kidney, fat, fascia & nodes) NO role for radiotherapy / chemotherapy Post operative immunotherapy reduces incidence of recurrence Approx 50% 5-yr post operative survival Transitional cell carcinoma Arises from urothelium (lining of ureter / renal pelvis) Uncommon below 40yrs. M:F = 4:1 Assoc with smoking, analgesic use & industrial carcinogens (rubber & cable industry + sheep dip), drugs (inc cyclophosphamide Tumours spread directly into muscle, renal parenchyma & fat Spread by lymph nodes rather than veins Presentation Haematuria, may pass clots 2o infection may mimic pyelonephritis Pain is a late symptom (showing invasion) Investigations IVU / retrograde urogram – shows filling defects Cystoscopy – used to visualise & biopsy CT & US of little help Management Usually are G3 at presentation  radical nephroureterectomy If low grade can use local resection Also give post operative radiotherapy to ensure no seeding along operative tract Renal Cysts Medullary sponge kidney Dilated collecting ducts with swollen honeycombed medulla Assoc with hemihypertrophy Infection  many small stones  repeated ureteric colic Scaring eventually  renal failure Obstruction cysts – back pressure of urine  cysts e.g. congenital multicystic kidneys due to ureteric obstruction e.g. aquired cysts due to pyelonephritis scarring e.g. diverticula of collecting system – normal to have 1 in all people e.g. congenital polycystic disease – AR, poor prognosis, often detected on neonatal US e.g. adult polycystic disease – AD (chr 16) usually diagnosed in adulthood. Assoc with cysts in liver & pancreas + berry aneurysms  SAH. Often asymptomatic. Can  HT, uraemia (eventually requiring transplant) & infection  Interpret an intravenous urogram / pyelogram, describe how it is performed and the reasons for requesting the test. IVU = intravenous urogram Renal 38 Uses iodobenzoate compound which is radioopaque Side effects Chemical phlebitis – due to local irritation by hypertonic contrast Nausea, vomiting & flushing – when bolus reaches systemic circulation Skin necrosis & blistering – if solution extravasates Allergy – can be urticarial or anaphylactic – ensure resus kit inc adrenaline, hydrocortisone & minitracheostomy kit are available Preparation Must be well hydrated (as can get contrast nephropathy --> renal failure) If on metformin must stop it 2 days before BEWARE if previous contrast allergy Films taken Control – to pick up any existing calcifications / other opacities 30 secs = “immediate” – contrast in renal parenchyma (glomerulo & proximal tubules) – can use tomograms to eliminate bowel gas shadows Compression – approx 15 mins with compression band to highlight & fill calices & pelvis Release – approx 15-20 mins on release of compression to show the ureters 1hr – to show bladder filing Post micturition to indicate residual volume  Be aware of other urinary tract imaging methods (ultrasound, CT scanning, retrograde pyelography) and their use. Ultrasound scans Good for imaging stucture of kidney & telling solid from cystic masses Very operator dependent Few SE as non-invasive MUST come with a full bladder Retrograde pyelography Contrast is injected by a catheter up into the ureter to fill the renal pelvis Usually done if IVU cannot be (contrast allergy / renal impairment) Should NOT be done if urine infection present as can cause pyelonephritis CT Uses less radiation than an IVU but costs more! Patient passes through a hoop to give transverse sliced images Air = -1000, Water = 0, Bone = +1000 (arbitrary hounsfield units) Should come with a full bladder to allow better imaging of the bladder  Surgical approaches to the kidney Posterior Percutaneous nephrostomy Needle passed through skin, latissimus dorsi, quadratus lumbrorum, perirenal fat & renal parenchyma to reach renal pelvis SE – needle is at risk of piercing pleura, liver, duodenum or colon 12th rib approach incision along the bed of the 12 th rib (in theory to avoid the pleura) 12th & 12th subcostal nerves + ilioinguinal & hypogastic are often stretched or cut Postoperative pain is common Vertical lumbotomy Vertical incision along lateral border of sacrospinalis gives limited access but avoids nerve damage of 12th rib approach Thoracoabdominal incision For large cancers where complete exposure is required for safety Renal 39 Incision through bed of 10th rib, across pleura & into abdomen Lung & liver are retracted Gives improved access to great vessels to allow better control of bleeding Anterior Extraperitoneal Through a cannula into perirenal fat a balloon is introduced to separate surrounding structures & kept inflated long enough to stop bleeding Can then be deflated leaving space for laparoscopic instruments Transperitoneal CO2 introduced & ports pushed through Conventional open Can use anterior transabdominal as transverse or vertical incision Common complications of renal surgery Pain – post operative pain on coughing & breathing  atelectasis & infection in lung (esp if pleura opened or rib removed) Pneumothorax Ileus – oedema or heamatoma behind bowel  abdominal distension & paralytic ileus Renal 40 The Bladder and Prostate  Discuss the management of trauma to the bladder (both accidental and surgical). General signs Severe pain (often settles) Abdominal distension & ileus – due to extravasated urine May be shifting dullness Absent desire to void, as pressure never builds up External penetrating injuries – any penetrating abdominal injury can include the bladder. Rx – close with absorbable sutures & leave catheter if for approx 1 week Internal penetrating injuries – e.g. injury through self catheterisation in patients with clam cystoplasty. Present as delayed perforation e.g. surgical trauma. Closed injury – e.g. drunk with distended bladder is run over. Bladder bursts  urine enters the peritoneal cavity. Diagnosis – Paracentesis finding blood  laparoscopy / otomy  find & repair tear Cystogram – contrast leaks into periteoneum if bladder is fully distended Cystoscopy – flexible cystoscopy will show the tear Treatment – if no evidence of peritonitis leave catheter for a week (to keep bladder empty) & recheck cystogram, ter should heal spontaneously Delayed perforation – 7 days post coagulation for CA bladder Initially no pain  few hours later distended abdo & absent bowel sounds Paracentesis  evil smelling fluid. Treatment – if no complications leave catheter. If in doubt – laparotomy, evacuate fluid & repair bladder  Describe the pathology, diagnosis, management and follow-up of transitional cell carcinoma of the bladder. 5th most common adult CA. M>F but F rising Most commonly TCC of urothelium – can be SCC / adenocarcinoma if metaplasia occurs Uncommon under 40yrs Risks Smoking (doubles risk) Occupational chemical exposure – dye, rubber, plastics, sheep dip Chemo / radiotherapy Chronic infection / inflammation (e.g. due to indwelling catheter, schistosomiasis etc) Pathology Mostly from transitional epithelium  papillary growth pattern (can also be solid / ulcer) Grade - G1-G3 (G3 = worst) 80% non-invasive, low grade (but 70% recur post resection – with 25% high grade & 10% invasive) 20% invasive high grade at 1st presentation Spread Direct spread – to surrounding fat & adjacent organs BUT NEVER crosses to rectum (although rectal CA often spreads to bladder) Implantation – via seeding to urethra & opposite bladder wall Lymphatic – once into detrussor muscle  nodes of internal iliac artery  bone marrow of pelvis, femur & lower vertebrae Systemic – occasionally seen in lungs, liver or brain Staging Using TMN system (see diagram) Renal 41 Screening If in “at risk” groups (chemical / rubber industry) have urine screened for malignant cells (large, multinucleated) Presentation Painless haematuria (>80%) – so scope all haematuria pateints Cystitis (masking as recurrent UTIs) with Sterile pyuria = CA until proven otherwise – frequency, pain on voiding, pus cells on urine microscopy but no cultured bugs Decoy prostate – can  irritable bladder & outflow obstruction. Test all prostate patients urine for blood & cytology Anaemia – due to continued blood loss Urinary infections – recurrent for no obvious reason in elderly (esp smoker) should be suspicious Pain – late sign Diganosis Urine shows sterile pyuria IVU shows filling defects Cystoscopy for direct visualisation & biopsy if required (must include muscle to allow staging) Bimanual EUA to assess spread within pelvis – e.g. muscle fixation CT/MRI to assess nodes Management Low stage resect via cystoscopy / diathermy / laser + regular FU with flexi transurethral resection of bladder tumour (TURBT) – if small papillary – remove muscle with tumour & send for histology. Must leave catheter 2-3 days. Risk of perf & bleeding Adjuvant treatments – BCG / mitomycin / adriamycin / epodyl as bladder chemo. Some role for immunotherapy Invasive (T2/3) Radiotherapy – used first to try cure / shrink before resection Total cystectomy – can replace bladder using a pouch of bowel  impotence Bladder & LN removed Urinary diversion Ileal conduit  urostomy OR neocystoplasty to urostomy / connected to urethra Follow up regularly to detect recurrence early  Discuss outlet obstruction of the bladder and list it's causes including mechanical and neurological causes. Failure of bladder emptying… Causes Failure of sphincter relaxation & detrussor contraction coupling High spinal cord lesions – detrussor contracts but the sphincter doesn’t relax Lesions at S2/3 – no reflex arc means detrussor doesn’t contract  overflow incontinence Enlargement of prostate (benign prostatic hyperplasia (BPH) & prostate CA) Stricture of the urethra Consequences Renal 42 Compensatory hypertrophy – of muscle fibres  trabeculation & urotheium begins to bulge out (saccules) & eventually outside of the bladder (diverticula). The detrussor muscle stretches with each effort to empty, weakening it Detrussor failure – when contractions cease. The bladder can no longer be voluntarily emptied  large residual volume with stone formation & infections. Can also get hydronephrosis Symptoms Slow flow, hesitancy, retention, dysuria, frequency, incomplete emptying, and pain  Describe the management of benign prostatic hyperplasia and its complications. Occurs in all men over 40yrs to some extent 1/10 will develop obstruction requiring treatment Size doesn’t tend to correlate with the degree of obstruction Pathology Smooth muscle – A1a-adrenoceptor cells hypertrophies & fails to relax Adenoma – any of the glandular tissue (with stroma) of the lobes can hypertrophy to obstruct the lumen Detrusor failure – initially bladder becomes stronger & irritable  weaker NB: acute retention is painful, chronic retention is painless Presentation Initially frequency with poor flow O/E – usually pale, wasted, may be confused Abdominally palpable bladder PR  can feel sulcus between lateral lobes of prostate Can progress to overflow incontinence, detrusor failure, diverticuli, bladder stones & infection, hydronephrosis & renal failure Investigations “International Prostate Symptom Score” (IPSS) – self reported incomplete emptying, frequency, intermittency, urgency, weak stream, straining, nocturia  score out of 35 + score quality of life Frequency volume chart Flow rate – less than 10ml/s = significant Residual volume – after urination Transrectal US – little relevance for BPH, done to exclude prostatic CA Urodynamics – assessing pressure during micturition – the only true test but rarely done as complicated (needs suprapubic catheter) & expensive Urine microscopy – for CA & blood cells as CA is always a differential PSA – again to check for cancer Differentials Cancer (see above) Stricture – more likely if previous catheter / instrumentation Neuropathy – inc central lumbar disc prolapse Polyuria – reduced ADH from pituitary in old age  nocturia Depression – cant sleep  cup of tea  urinate & cant sleep Management  Watch & wait (approx 6 month is usual)  A blocker – (prazosin) if frequency is the main problem – cause relaxation of smooth muscle  Finasteride (5A-reductase inhibitor) – prevent testosterone  dihydrotestosterone (4x more potent) acting on prostate cells  glandular regession, will also cause PSA to drop  Surgery – if incontinence, haematuria, retention or recurrent UTIs Renal 43     TURP – transurethral resection of prostate  Complications inc bleeding, stricture, retrograde ejaculation, impotence (10-15%), incontinence (small risk)  Short term risk or TUR syndrome = hyponatraemia & cerebral oedema  delerium – Rx with diuretic (mannitol) TUIP – transurethral incision of prostate  Less bleeding, shorter stay, results not as good, no tissue for biopsy Open prostatectomy Discuss the presentation, staging, pathology and clinical management of carcinoma of the prostate including a description of hormonal manipulation. 2nd most common malignancy in men Tends to be adenocarcinoma Risk factors Incidence increasing due to people living longer At age 50, 15% of prostates have some CA, by 80 yrs = nearly 100% More common in Africans, less common in Japanese & Indian +ve family history Histological grades Gleason system – Grades 2 high power fields from 1-5 then add the scores together WHO scoring – G1-3 Staging Based on spread to bladder or seminal vesicles, surrounding the rectum or to LN Tumour markers - Prostate specific antigen (PSA) Protein secreted by all prostate cells (benign & malignant) Can then be measured in blood or detected in immunofluoresence on tissue section Is used for both screening & follow up Poor sensitivity & specificity - & levels don’t always correspond with severity (except in levels in the thousands) Presentation Indicental – Often detected on routine PSA check / seen on US scan performed before TURP Symptoms Prostatism – exactly the same as BPH symptoms Rectal obstruction – if CA surrounding  pencil thin stools & constipation Uraemia - due to ureteric obstruction  hydronephrosis Distant mets – pathological # or spinal cord compression due to bone mets Investigations DRE – enlarged, hard, irregular prostate / nodule within prostate Transrectal US – with US guided biopsy CT scan – to allow full staging MRI – is more detailed at looking for staging Bone scan – hot spots are due to increased vascularisation (false +ves due to rib # or Osteoarthritis) Management Hormonal treatment - many of the CA cells are stimulated by testosterone Orchidectomy – removes the cells which produce testosterone Diethylstilboestrol – synthetic oestrogen to block metabolism of testosterone GnRH-agonists – (zoladex) overstimulate the pituitary until it is exhausted & can produce no more LH. Will cause an initial flare of the CA unless given with testosterone blocker = chemical orchidectomy 5a-reductase inhibitors – (finasteride) prevents testosterone  dihydrotestosterone (4x more potent) Radical prostatectomy – lower abdo incision  removal with LN SE – urinary incontinence, impotence, retrograde ejaculation, urethral stricture, urethral stricture Radiotherapy – very good for bone mets Renal 44 Continence 200 million worldwide 14% women, 6% men at ALL ages Assoc with increased risk of falls & # Incontinence = involuntary loss of urine which is objectively demonstrated and a social/hygienic problem Impact Embarrassment Fear Restriction of fluid ( dehydration) Limited social life Affects sex life Costs of management Anatomy of Continence Frontal cortex = Voluntary control Pontine micturition centre = co-ordination Sacral cord roots  detrussor muscle = parasympathetic Pudendal nerve  bladder outlet = sympathetic Storage = sympathetic (T12-L2)  high urethral pressure Voiding = parasympathetic (S2-4)  high detrussor pressure In men the continence mechanism has 3 parts Internal urethral sphincter (part of the prostate & bladder neck muscle) External urethral sphincter (voluntary sphincter) Bladder neck being within the abdomen – so changes in abdominal pressure increase both sphincter & bladder pressure In women the mechanism is the same but women lack the internal sphincter In the elderly 10% have detrussor instability Decreased capacity Increased residual volume (>100ml  infection  irritation) Increased prostatism in men  residual volume Insults (pathological, physiological, psychological, pharmacological) Type of Incontinence 1. Outlet weakness = GSI – involuntary loss when bladder stable & non contractile due to transient increases in intraabdominal pressure (e.g. cough). Common post partum / post prostatectomy 2. High pressure = Urge incontinence – profound urge to void associated with nocturia & frequency. Detrussor instability = spasms – can be idiopathic, neural damage, outlet obstruction  residual vol  irritation  contraction 3. Mixture of 1 & 2 (upto 15% in elderly women) 4. Overflow = prostatic hypertrophy or neuropathic bladder. Rx by relieve obstruction 5. Fistulae = often to bowel / vagina Transient incontinence (DIAPERS) should be treatable (30% community, 50% hospital) Delerium Infection Atrophy (vagina) Pharmaceutical (diuretic, anticholinergic, antipsychotic, antidepressant, sedative, narcotic, A-blocker, A-agonist, Ca2+ blocker, ACE Inhibitor, Alcohol) Excess UO (DI, DM, diuretic) Renal 45 Restricted mobility Stool impaction (presses on bladder) History Include – sexual, O&G, pelvic/abdo surgery, DH, Functional, Social, Mental Frequency/Volume chart (input = what, when, how much, output = continent/hr) Examination Full clinical, genital, digital rectal (for prostate), vaginal Investigations Urinalysis – MSU/CSU (via catheter) Uroflowmetry (wee into bucket) / Urodynamics (pressure/contrast) Management Conservative  Check fluids (Vol, caffeine, alcohol), fluid habits (timings), diet (no curry) & toileting  Review existing meds (consider laxatives, reduce sedatives)  If transient – treat cause Stress Incontinence  Barrier methods if only small volume  Pelvic floor exercises (limited use in elderly people) +/- vaginal cones to check technique, +/- electrical stimulation of pelvic floor muscles to assist with training  SNRI (selective noradrenalin reuptake inhibitor) e.g. duloxetine  Surgery – TFVT Detrussor Instability  Bladder Training to extend times between toileting, works well if motivated  Antimuscarinic drugs – SE include confusion, more selective = less SE 1. oxybutinin 2. tolterodine 3. trospium ? 4. solifenacin ? 5. darifenacin ?  Ca2+ antagonists  Botox injections to the bladder neck Overflow Incontinence  Clean intermittent self catheterisation for neuropathic bladder  Queens square stimulator  A-blockers / 5 A-reductase inhibitors to reduce prostate size  NB: avoid long term catheter wherever possible as  infection, atrophy of bladder & loss of self continence. Also inconvenient and predictive factor for entry to nursing home. Use Flip-Flow valve to maintain voiding cycle & bladder volume – no bag and easier to wean patient off. Renal 46 Urinary Tract Infection > 105 colonies / ml  Describe the symptoms and signs of urinary tract infection Cystitis Increased frequency, urgency, dysuria, haematuria, suprapubic pain Acute pyelonephritis Fever, rigors, vomiting, loin pain & tenderness, (may be oliguria) Prostatitis Flu like symptoms, low backache, swollen & tender prostate, few urinary symptoms Non specific Confusion in elderly patients Failure to thrive in children Septicaemia & septic shock in immunocompromised  List the factors that may predispose to urinary tract infection Female Intercourse – esp with use of diaphragm contraceptive / vaginal spermicide Pregnancy Menopause Renal or bladder obstruction (stones, instrumentation or congenital malformation Diabetes Vesicoureteric reflux.  List the common pathogenic bacteria associated with urinary tract infection Mainly E.coli (>70% in community, 40% in hospital) Others include staph saphrophyticus, enterococcus faecealis, proteus mirabilis, kebsiella, enterbacter, acinetobcter, pseudomonas & serratia marascens, TB??  Outline the investigation of a patient with a suspected infection. MSU - Dipstick, microscopy & culture Bloods - FBC, U&E, CRP, cultures Imaging IF infants, men, recurrent UTIs, pyelonephritis, haematuria or persistent fever US first as avoids radiation IVU will detect stones, papillary necrosis, small CA or clubbed calyces Cystoscopy to visualise  Discuss the general treatment measures and suitable antibiotic regimens for treatment. Treatment Drink large amounts of fluid, urinate often Avoid Abx until infection confirmed – then follow sensitivities. If empirical treatment required then consult local policy Prevention Abx prophylactic – or as a single dose as soon as patient has Sx Drinking cranberry juice  Describe the pathological features and complications of acute and chronic pyelonephritis. Pyelonephritis - Acute suppurative bacterial infection of kidney and renal pelvis Bacteria can reach the kidneys via 2 routes Ascending infection – from the LUT. Predisposed by pregnancy, DM, urine stasis & reflux Blood stream spread – more unusual. Usually in elderly patients with PUO Renal 47 Acute Macroscopic - Variable numbers of small, yellow/white cortical abscesses Histology - Neutrophil infiltration Chronic Chronic inflammation & scarring  destruction of nephrons & distortion of collecting system Extends into pyramids- necrotising papillitis (renal papillary necrosis) Extend thru capsule perinephric abscess Associations Urinary obstruction History of intrumentation/ catheterisation Vesicoureteric reflux Pregnant- 3% may develop UTI Female upto age 40 common (older males usually BPH) Preexisting renal lesions (scarring) Diabetes Clinical features Pain costo- vertabral angle Fever malaise dysuria frequency Urgency Pyuria White cell casts indicate renal involvement as apposed to having only cystitis Course Generally resolve rapidly with antibiotics However high incidence of recurrent infections if underlying predisposing causes not corrected Persistent bacteriuria may eventuate in chronic pyelonephritis especially in those with vesicoureteric reflux Complications Recurrence Perinephric abscess Sepsis & septicaemia Acute renal failure  Discuss the diagnosis of bladder infection outlining the importance of confirming significant bacteriuria (>100,000 organisms/ml) and the importance of white cells in the urine. “cystitis” – inflammation (& infection) of the bladder infection is significant when > 100,000 org /ml Symptoms Frequency, dysuria, urgency, strangury, haematuria, suprapubic pain WBC in urine (pyuria) Management Increase fluid intake Urinate often & double void Post intercourse voiding Wipe front to back Abx – usually trimethoprim Renal 48 Sexually transmitted infections  Discuss the main aspects of the sexual history and the differentials for the main female presenting complaints Sexual history Most recent exposure – when, regular/casual partner, if regular how long for, contraception/protection, condom breakages/slips, has partner got symptoms Previous sexual partner – how long ago (if past few months get all details above), how many partners over past few months Related to HIV – ever injected drugs? Are any male partners bisexual, injecting or from high risk areas (asia/sub Saharan Africa) Symptoms Asymptomatic 80% chlamydia, 50% gonorrhoea, 65% PID, 30% genital warts, 50% genital herpes Vaginal Discharge Ask about odour, vulval itching, soreness, dysuria, IMB, PCB, abdo pain Vaginal infections – bacterial vaginosis, candida, trichomonas Cervical infections – chlamydia, neisseia gonorrhoea Physiological discharge – cervical ectopy Other causes – retained tampon, retained products of conception Dysuria Usually acute bacterial cystitis, urethritis and vulvitis Is it external (as urine touches vulva), frequency, urgency, nocturia, haematuria, vaginal discharge, PCB, abdo pain, vulval sores, itching Acute bacterial cystitis – coliforms, staph saphrophyticus Urethritis – chlamydia, neisseria gonorrhoea Vulvitis – genital herpes, candida, trichomonas, vulval dermatological conditions Vulval Lumps Due to infection, anatomical variants etc Are the lumps painful, how many, how long for, any other symptoms Viral infections – genital warts, molluscum contagiosum, VIN & vulval cancer Bacterial infections – syphylitic condylomata lata, skene’s or bartholins abscesses (chamydia/gonorrhoea) Others – anatomic variants, vulval papillae, sebaceous cysts Vulval Ulcers Most commonly infection (genital herpes most common) Are they painful, how many, how long for, any other symptoms Infective – genital herpes, syphilis Non infective – aphthous ulcers, behcets syndrome Lower Abdominal Pain Many causes, most common group for infective is under 25’s Any discharge, PCB, ICB, deep dyspareunia, last LMP, contraception, ?pregnant, any other symptoms Uterus – endometritis (chlamydia, gonorrhoea, bacterial vaginosis), endometriosis Tubes – salpingitis (chlamydia, gonorrhoea), ectopic Ovary – torsion, haemorrhage into a cyst Other – cystitis, acute appendicitis, IBS  Discuss the diagnosis and management of urethritis Urethritis = discharge, dysuria & discomfort (but 10-15% have no symptoms) Usually divided into gonococcal & non-gonococcal (NGU) Non-gonococcal – Sexual causes include chlamydia, trichomonas vaginalis, mycoplasma genitalium, bacteroides & HSV. Syphilis causes inflammation by chancres within the penis. Renal 49 Non sexually transmitted urethritis can be caused by UTI, prostatic infection, foreign bodies & strictures Features – mucoid discharge, worse in the morning, with crusting at the meatus & in underwear. Dysuria is common but not universal. Discomfort / itch can occur. Incubation 1-5 weeks (mean = 2-3 weeks) Diagnosis – smears after holding urine for at least 4 hrs  gram stain. >5 polymorphoneuclear leucocytes / high power field = diagnostic Treatment – doxycycline 100mg 12hrly / azithromycin 1g oral. Avoid intercourse. Trace partners Recurrent NGU – 20-60% of acute cases will recur (2-3 weeks post treatment). Check adherance to treatment & abstinence Neisseria Gonorrhoea Gram –ve intracellular diplococci Causes inflammation of the paraurethral glands Sx – pus, painful urination, oedema (may  cordee). If untreated  urethral stricture  Discuss the main sexually transmitted diseases, their significance and management. Chlamydia trachomatis Most common STI (3-5% of sexually active women, 14% of under 20’s,). Usually cervix, + 50% urethreal Importance - Can cause vaginal discharge, increased/irregular bleeding, PID, infertility (tubal damage) & ectopics, ovarian, skenes & bartholins abscess, endometritis, salpingitis, perihepatits. In pregnancy – can cause miscarriage, preterm birth, postpartum & neonatal infection. Can cause reactive arthritis, increase HIV risk, some links to cervical cancer In men – epididymo-orchitis, discharge & dysuria Symptoms - 80% asymptomatic, increased discharge, dysuria, If extensive - lower abdo pain, IMB O/E – can cause mucopurulent cervicitis, contact bleeding, may look normal Testing offered to – anyone symptomatic, @ GUM, wanting TOP, under 25s, new partner or > 2 partners in last yr Diagnosis – swab is best (look for organism), or urine (for antigen) Management – If male/not preg – 1g azithromycin (stat) – (not if preg/breast feeding, allergic, liver disease, renal impairment) Otherwise – 100mg doxycycline b.d for 7 days - (not if photosensitivity, avoid Fe & indigestion remedy, risk of candida) Neisseria Gonorrhoea Sexually aquired in adults - Cervix & urethral infections (70%) Importance – can  abscesses, endometritis, salpingitis (10-20%), perihepatitis, ectopics, infertility, acute arthritis, dermatitis, increased HIV risk In pregnancy – can cause miscarriage, preterm birth, postpartum & neonatal infection Symptoms – 50% asymptomatic. Increased discharge, dysuria, PCB, If extensive – lower abdo pain & IMB O/E – purulent or mucopurulent cervicitis, contact bleeds, may look normal. Management – ciprofloxacin / ofloxacin / ampicillin / ceftriaxone Pelvic Inflammatory Disease Due to infections ascending into upper genital tract (endometritis, salpingitis, tubo-ovarian abscess, pelvic peritonitis) Importance – major problem is tubal damage. Each episode increases damage & therefore ectopic risk Causes – mainly chlamydia (mild) & gonorrhoea(more severe), mycoplasma hominis & anaerobes also found. Renal 50 Symptoms – onset in 1st part of cycle. Lower abdominal pain (most common), increased vaginal discharge, irregular bleeds, deep dyspareunia, dysuria O/E – mucopurulent discharge with contact bleeding (indicative of cervicitis), adnexal & cervical ternderness, pyrexia, palpable adnexal mass Diagnosis – no specific test available. May be raised ESR, CRP, WCC. Microbiology samples are gold standard. Diagnosis usually made based on clinical findings & LGT swabs. ALWAYS exclude ectopic pregnancy Management – admit if diagnostic uncertainty, severe case or failure to respond to oral therapy. Empirical treatment until organism known (minimises tube damage) IV if severe. Give appropriate analgesia Bacterial Vaginosis Overgrowth of anaerobic bacteria, genital mycoplasmas and gardnerella vaginalis NOT sexually transmitted so partners do not need to be treated Most common cause of vaginal discharge in women of reproductive age Importance – increases vaginal cell cuff following procedures, increases HIV risk In pregnancy – increases risk of late miscarriage and preterm birth Symptoms – 50% asymptomatic. Mainly increased discharge and fishy odour (worse with sex & period) O/E – milky white discharge, may be frothy, adheres to vaginal wall Diagnosis – Amsels criteria (at least 3 of the following): typical discharge, vaginal pH > 4.5, amine odour with 10% KOH, clue cells on microscopy. Can use gram stain vaginal smear. Culture is not used (due to high colonisation rate of normal women). Management – in all women with symptoms, undergoing TOP & pregnant with previous preterm birth. Metronidazole or clindamycin Candida infections Very common – 75% lifetime risk, increased if pregnant, immunosupression or uncontrolled DM NOT sexually transmitted – partners do not need treatment. No long term complications Symptoms – vulval itching (nearly all symptomatic cases). Thick white discharge, vulval burning, external dysuria, superficial dyspareunia O/E –vulval erythema, fissuring, oedema, white plaques on vaginal walls Diagnosis – by culture Management – topical clotrimazole / econazole / miconazole, oral fluconazole / itraconazole Trichomonas Vaginalis (TV) Relatively rare in UK (common in Africa & Asia). Sexually transmitted. Only in urogenital tract Importance – Increased risk HIV, low birth weight & preterm delivery Symptoms – asymptomatic (10-50%). Vaginal discharge, odour, pruritus, external dysuria, dyspareunia Diagnosis – culture Management – metronidazole, check for other STIs Genital Warts Painless, benign, epithelial tumours causes by HPV 6 & 11 Highly infectious, incubation average 3 months (up to yrs). Commonest viral STI in UK Importance – Cervical cancer. vertical transmission can occur Symptoms – painless so many asymptomatic. Vulval lumps, flesh coloured papules Diagnosis – by clinical appearance, biopsy if in doubt Management – topical cytotoxics, imiquimod, ablative therapy Genital Herpes Due to HSV 1 or 2 Initially acute vesicular / ulcerating eruption  recurring lesions (gets into DRG) Renal 51 Importance – life long infection. Risk of vertical transmission in 3 rd trimester, increased HIV risk, psychological fear, rejection by sexual partners, meningitis, neuropathy Symptoms 1o infection – vulval soreness, external dysuria, multiple painful superficial ulcers + tender lymphadenopathy Symptoms 2o infection / recurrence – may be asymptomatic but still infectious, a few ulcers in limited area Diagnosis – by viral culture Management 1o – antivirals (acyclovir, famcyclovir, valacylovir), analgesia, saline bathing, PU in bath to lessen pain, explain recurrence risk Management 2o – self limiting so support, antivirals may hasten recovery Syphilis (Treponema Pallidum) Is sexually transmitted in adults Importance – miscarriage, still birth, congenital syphilis Symptoms – asymptomatic, primary – chancre (single painless ulcer with rolled indurated edges) which often goes unnoticed, secondary – generalised illness, fever, malaise, skin, mucosal rashes (trunk, limbs, palms & soles), warty papules on vulva, Late – neurosyphilis, cardiovascular or gummata Diagnosis – serology Management – long course of antibiotics required with intense follow up HIV Spread by contact with body fluids, now routine in antenatal testing Importance – lifelong illness. Treatment in pregnant mothers reduces vertical transmission Symptoms – asymptomatic for several years, mild systemic illness (fever, malaise, rash) at seroconversion, increase in other infections, opportunistic infections become serious Diagnosis – serology – patient must consent to test Management – monitor viral load and CD4, antiretrovirals when CD4 < 350 x 109/l, prophylaxis for pneumocystis if CD4 < 200 x 10 9/l Renal 52 The Urethra, Penis and Scrotum  Discuss the management of trauma to the urethra. Iatrogenic trauma Usually due to pressure injuries from instruments, particularly catheters Perineal injury Usually during sports Blunt force compresses the bulbar urethra against the inferior edge of the pubic symphysis  tearing the corpus spongiosum & urethra  urine & blood escape to the scrotum  necrosis of fat & penile skin Treatment – avoid leakage of urine by draining the bladder for 10 days by suprapubic catheter. Check healing 10 days later by flexible cystoscopy – the urethra has usally healed completely by this point. If a stricture does form it will be short and easy to treat Fractured pelvis with rupture of membranous urethra Membranous urethra is attched to prostate & to ischiopubic ramus by corpus cavernosa. If #  tension between these the urethra will stretch then tear Minimal displacement – due to compression of pelvis (e.g. car trapping man by a wall). The symphysis moves backwards into the pelvis  S-shaped bend in urethra (or tear). Manage by draining the bladder by suprapubic catheter & anastomosing / incising the S stricture Gross displacement – due to major forces (e.g. car crash)  major tear, will require significant reconstruction Complications Stricture, Impotence, Impaired ejaculation, Incontinence  Describe the aetiology, presentation and management of a urethral stricture. Can be caused by inflammation, scar tissue, surgery, disease, injury or external pressure Risks STDs (in men), urethritis, BPH Symptoms - Same symptoms as outflow obstruction due to prostate Dysuria, Slow stream, low output , Frequency & urgency Incontinence (overflow), Retention Blood in semen / urine, Urethral discharge, Swelling of penis Complications Urinary infections – infected urine being forced into the paraurethral ducts  further urethritis & progressive scarring Paraurethral abscess – infection  pus & suppuration. May  fistulae & stones Sterility – semen may be unable to pass the stricture (urine is unaffected as is less viscid) Cancer – in longstanding strictures squamous CA may occur Investigations Flow rate – to show the severity Urethrography – will show the stricture but not surrounding scarring & fibrosis Flexible cystoscopy – for direct visualisation Management Suprapubic catheter to relieve retention Regular intermittent dilatation can be performed at home or in hospital Internal urethrotomy – using endoscopy to cut the stricture Dilatation of the urethra by catheter / stent / surgery Appendicovesicostomy (allows self catheterisation by bladder wall)  Describe the pathology, presentation and management of: o Phimosis  Foreskin which cannot be retracted proximally over the glans  Can be congenital / poor hygiene / chronic balanoposthitis Renal 53 o o o o o o o   Managed by circumcision if symptomatic Paraphimosis  Foreskin is retracted and cannot be replaced  Swelling, tenderness & erythema in glans  Oedema of distal foreskin  Flaccidity of shaft proximal to paraphimosis  Managed by squeezing glans for ½ hr or 50% dextrose swab to reduce swelling Priapism  Persistent painful erection (often with a flaccid glans)  Arterial - rupture of the cavernous artery  unrestricted inflow  Venous – veno-occulusion  impaired drainage  Managed by ice to pelvis & perineum, walking up stairs, A-agonists or aspiration of blood Peyronie's disease  Penile fibrosis  angulation of erection  Linked with injury, circulatory disease & diabetes  Many cases resolve spontaneously – Otherwise managed by surgery & prosthesis Carcinoma of the penis  1/100,000 men  can be caused by phimosis / poor hygiene, linked to smoking & recurrent balanitis  presents with painless sore / ulcer on foreskin / glans, balanoposthitis & discharge  Graded G1-3 based on histology, staged based on extent & spread  Managed by surgery (amputation), circumcision, wedge resection, laser surgery, radiotherapy & lymph removal Varicocoele  Physiological dilatation of the pampiniform plexus – “bag of worms”  Linked with infertility  Managed by surgery Hydrocoele  Accumulation of serous fluid adjacent to the testis (in tunica vaginalis)  Fluctuant and transilluminates  Can be congenital – due to persistent processus vaginalis  Or aquired in adulthood – usually idiopathic  Manage by draining & everting the tunica vaginalis to prevent reaccumulation Epididymal cyst  Benign tender cyst of epididymis – in communication with the epididymis so fills with sperm  Always fluctuant and transilluminates  Confirm by US  Managed by surgical removal otherwise they will recur Outline the causes of male erectile dysfunction and list the available treatments including vacuum tumescence devices and intracavernosal injection therapy. During arousal the A-V anastomoses of the cavernosa are closed (due to parasympathetic stimulation)  cavernosa spaces are follied Bulbospongiosus & ischiocavernosus compress the venous plexuses at the outfow impeding venous return During emission – semen (sperm + gland secretions) is delivered to prostatic urethra through ejactulatory ducts following peristalsis of ductus deferens & seminal glands. Prostatic fluid is added to the seminal fluid as the smooth muscle in the prostate contracts During ejaculation semen is expelled due to: Sympathetic closure of urethra sphincter @ neck of bladder (L1-2) Parasympathetic contraction of prostatic & urethral muscles (S2-4) Contraction of bulbospongiosus muscles – pudendal nerve (S2-4) After ejaculation sympathetic stimulation allows constiction of muscle in coiled arteries & bulbospongiosus & ischiocavernosus muscles relax allowing venous return “Erectile dysfunction” – inability to get / maintain erection Renal 54 Usually temporary & resolves spontaneously Considered a problem if persists more than 25% of the time Causes DM, HT, heart / thyroid conditions Poor circulation Low testosterone Depression, spinal cord injury, nerve damage B-blockers, digoxin, antidepressants Nicotine, alcohol, cocaine Stress, fear, anxiety, anger Poor communication with partner Failure  doubt  anxiety  further failure Treatment Treat any underlying cause (e.g. hormone imbalance) Viagra (sidenafil) Testosterone by skin patch / injection Penile injection – alprostadil  increase blood flow Vacuum pump Penile implant  Outline the cause of non-descent and mal-descent of the testis, the risks of this condition and its management. Non-descent / incomplete descent Still along the path of the gubernaculums but not reached the scrotum Abdominal (inside internal ring) Inguinal (within the inguinal canal) Emergent (appearing at the external inguinal ring) High retractile (move up and down but will not reach the bottom of the scrotum Low retractile (will reach the bottom of the scrotum with pursuasion) Mal-descent = ectopic within the body Due to bad attachment of the gubernaculum Abdominal wall – near the internal inguinal ring Penile – near the base of the penis Crural – in the perineum / thigh Complications Torsion – due to poor anchoring in the loose peritoneum Infertility – with bilateral undescended due to higher temperatures Cancer – 1/10 testicular tumours are assoc with maldescent. It is also more difficult to monitor for growths Management Ectopic testes require orchidoplexy Non-descended require bringing down into the scrotum in stages  Discuss the pathology, presentation, diagnosis and management of torsion of the testis. More commonly occurs on the RHS Can be predisposed by inadequate connective tissue, trauma or strenuous exercise Symptoms Sudden onset of severe testicular pain Scrotal swelling Nausea & vomiting Light-headedness Testicle on affected side is higher Differentials Mumps orchitis – never occurs before puberty Epididymitis – always secondary to obvious UTIs Fat necrosis – occasionally seen in infants Renal 55 Cancer – in older boys & men presents with inflammation Torsion of an appendix testis Management Surgery ASAP – can usually save testicle if with 6 hrs Also fix the other side at the same time  Discuss the pathology, presentation, diagnosis and management of epididymo-orchitis. “Epididymo-orchitis” – inflammation of one / both testis Usually caused by infection (mumps, honorrhoea & chlamydia) Risk factors  Inadequate mumps vaccination  45yrs  recurrent UTI  Abnormality of urinary tract  GU surgery / instrumentation  Long term catheter  Multiple sexual partners / other high risk sexual activity Symptoms  Scrotal swelling – tender & “heavy”  Fever  Penile discharge  Dysuria  Pain in groin & on intercourse / ejaculation  Blood in semen Diagnosis  Urinalysis & culture  Uretheral smear (for gonorrhoea & chlamydia)  FBC  Doppler US – to exclude torsion & show blood flow (usually increased) Management  Analgesic & anti-inflammatory  Bed rest  Ice packs on scrotum  Treat any infectious cause  Discuss the pathological classification of tumours of the testis and their biological behaviour. Discuss the management of seminoma and teratoma of the testis. Most common CA in men under 35yrs 1/10 occurs in assoc with maldescent of the testes Classification  Seminomas (30-40%) o 30-40 yrs o usually localised (25% lymphatic spread)  Embryomal CA (20%) o 20-30 yrs o highly malignant  liver & lung  Yolk sac tumour o 60% of CA in young boys  Teratoma o 7% in adults, 40% in young boys  Choriocarcinoma o Rare  Stroma tumour o Leydig, sertoli & granulose cells Renal 56 o 3-4% of testicular tumours o Secrete oestrodiol  gynaecomastia Symptoms Enlargement / change in feel to testicle / inflammation Dull ache in back / lower abdomen – usually due to mets to back Gynaecomastia – due to trophoblastic elements secreting HCG Testicular discomfort / pain / “heavy” Staging T stage – from examination of the testis N stage – para-aortic nodes – localise with CT M stage – occur early with the trophoblastic elements Treatment Orchidectomy & lymphadenectomy Radio & chemotherapy  reduce recurrence & increase survival NB: CA of testis mets to lumbar LN, CA of scrotum mets to superficial inguinal LN Renal 57