Flashcards in Genitourinary I Deck (57)
Fluid and electroyte function
1) Approximately one-fifth of the cardiac output
passes through the kidneys each minute, resulting in a renal blood flow of up to 400 mL per 100 g of kidney per min (650 mL/min per kidney). The renal blood pressure remains extremely constant despite profound changes in systemic blood pressure, and the survival advantage of this mechanism is apparent on reflection.
2) This phenomenon is described as autoregulation
and is principally mediated via effects on preglomerular vascular resistance. Whilst the underlying mechanism is the subject of intensive study, it is thought to be related to intrinsic myogenic tone within blood vessels, independent of neural factors.
A total of 170–180 L of plasma per day are filtered
through the glomeruli at an approximate rate of
125 mL/min. The glomerular membrane acts as a main fi ltration mechanism and is impermeable to molecules larger than 4 nm diameter, which relates to an average molecular weight of 70 000 Da. The ultrafi ltrate of plasma then passes down to the tubules.
1) The proximal tubule This decreases the volume
of glomerular fi ltrate by 75–80%, with active resorbtion of glucose, phosphate, bicarbonate, potassium and chloride.
2) It is important to realise that glucose is resorbed entirely from the proximal tubules, unless the glucose load exceeds the capacity for absorption. The majority of fi ltered sodium and bicarbonate are reabsorbed from the proximal tubules, and sodium is actually pumped via hydrogen/potassium-linked pump mechanisms.
3) The proximal tubular fi ltrate is iso-osmotic as a consequence of passive absorption of both water and urea. Sulphates, amino acids and low molecular weight proteins are reabsorbed, as is
Loop of Henle
1) Sodium chloride and water are resorbed passively. Water is resorbed from the moreproximal part (descending limb) in combination with sodium, whilst the distal part (ascending limb) is impermeable to water, with active sodium resorbtion.
2) This produces a concentration gradient in the renal medulla which is important in maintaining water balance. Loop diuretics, e.g. furosemide, inhibit chloride and sodium resorbtion from the descending limb.
Distal tubule and collecting duct I
1) The filtrate is hypotonic as it leaves the loop of Henle, entering the distal tubules where water resorbtion is under the control of anti-diuretic hormone (ADH).
2) Sodium is actively pumped out of the distal tubules, and resorbtion is modified by aldosterone secretion. The collecting tubules pass through the renal medulla, and water absorption is independent of sodium resorbtion and is regulated by ADH secretion.
Distal tubule and collecting duct II
1) Sodium is actively pumped out of the collecting tubules against a concentration gradient to maintain the hypertonicity of the renal medulla, with associated passive resorbtion to a small degree.
2) Large amounts of urea also are resorbed passively from the collecting tubules. A number of substances are secreted in the distal tubule,
including potassium and hydrogen and drugs. At this level 75% of the potassium content of urine results are due to tubular secretion.
3) Potassium secretion is linked with sodium and hydrogen concentrations and is modifi ed by aldosterone secretion. Hydrogen secretion occurs in the distal tubules against a concentration gradient.
Water balance: Loop of Henle I
1) Sodium and chloride are transported out
of the ascending limb of the loop of Henle, and the
sodium concentration falls progressively as the distal tubule is reached. The remainder of the loop of Henle is in osmotic equilibrium with the substance of the kidney.
2) As the iso-osmolar filtrate reaches the bottom of
the loop of Henle the contents of the descending limb become more concentrated as a result of being pushed towards the ascending limb.
Water balance: Loop of Henle II
1) Further concentration occurs due to active sodium resorbtion in the ascending limb, resulting in an osmolar gradient in the renal medulla.
2) Any increase in medullary blood flow results in dissipation of medullary osmolality, decreased water
resorbtion and the production of large quantities of
3) Dehydration results in release of ADH, increasing permeability in the distal nephron and results
in increased water resorbtion. ADH is released from
the posterior lobe of the pituitary gland.
4) The endogenous control of ADH release is under the regulation of osmoreceptors adjacent to the supraoptic nucleus, which is under the infl uence of sodium and chloride concentration in the plasma. There are also volume receptors in the atria and great veins which seem to be under the control of the vagus nerve.
Acid base balance
The kidney cannot excrete urine of pH < 4.5. Maintenance of acid-base balance relies upon a complex series of buffer mechanisms.
1) In the proximal tubules the predominant buffer system is dependent on bicarbonate HCO3
-/H2CO3, whilst in the distal tubules the
predominant buffer is HPO4 2"/H2PO4- and the weakest is the ammonium NH4+ system.
2) The phosphate buffer system is the most important during normal renal function, but the NH4+ system has a particular advantage in that it allows excretion of acid without loss of metallic cations such as Na+.
Hormone production by the kidney
1) A number of important hormones are produced within the kidney. The renin-angiotensin system is important, with renin being released from juxtaglomerular cells in response to sympathetic nerve stimulation via a decrease in afferent arteriolar pressure and hyponatraemia.
2) Renin acts on circulating angiotensinogen
to produce angiotensin I, which is converted by a
circulating enzyme to angiotensin II.
3) Angiotensin II stimulates the zona glomerulosa of the adrenal gland to produce aldosterone, which increases the sodium resorbtion by the kidneys and also produces vasoconstriction.
4) These effects feed back in a negative fashion
and switch off renin secretion and, therefore, maintain homeostasis. This is a gross oversimplifi cation of an extremely complex system, but nevertheless it is evident that this homeostatic mechanism is essential to maintain a smooth blood pressure and compensate for changes in extracellular fl uid volume and sodium excretion.
Other important hormones which are the subject
of contemporary study include kallikrein (produced
in the distal nephron) and other related agents. These substances are important vasodilators and also have been shown to have motor effects within the lower urinary tract and may be involved in sensorimotor mechanisms within the bladder.
Calcium and Kidney
The kidney is also involved in calcium metabolism
and produces 1 alpha-hydroxylase in response to low circulating levels of calcium, which acts to convert 25-hydroxycholecalciferol into the active metabolite 1,25-dihydroxycholecalciferol, which then promotes calcium reabsorbtion and decreases urine excretion to maintain homeostasis.
Erythropoietin is produced by the kidney in
response to hypoxia (either due to anaemia or respiratory causes), high circulating levels of the products of red cell destruction, and vasoconstriction. It is also produced in smaller amounts by the liver and spleen.
Erythropoietin stimulates an increase in the number of nucleated red cells in the haemopoietic tissue, thereby raising red cell and reticulocyte counts in peripheral blood. Indeed synthesised erythropoietin is used in contemporary haematological practice, for these very purposes, especially in intractable anaemia associated with chronic renal failure.
Nephrotoxic drugs include heavy metals, organic solvents, radiological contrast media (the combination of radiological contrast
plus metformin has recently been recognised as
being toxic), antibiotics such as aminoglycosides and some cephalosporins, chelating agents, paraquat and penicillamine.
Ureteric obstruction can occur either as a direct result of drug action (predominantly of historical interest now), e.g. retroperineal fibrosis due
to methysergide and practolol or as a consequence of blockage of the ureters due to renal papillary necrosis consequent upon analgesic abuse.
Uric acid stones
Uric acid stones can result from the use of high dose aspirin, thiazide diuretics and furosemide. Increased symptoms can result from the effect of agents increasing urine production, e.g. diuretics, or acting directly on the bladder; and relative underactivity of the bladder possibly leading
to retention can result from anticholinergics, particularly if there is an additional factor such as obstruction to the bladder outlet.
Acute renal failure
This is an abrupt decline in renal function with a loss of normal activity. A daily urine output of less than 500 mL is termed oliguria; the absence of urine formation is anuria. The underlying cause of acute renal failure is a persistent fall in renal blood fl ow to levels 30–40% of normal with a consequent reduction in glomerular fi ltration to less than 5 mL/min. The causes of acute renal failure can be divided broadly into prerenal, renal and postrenal.
Prerenal acute renal failure usually results from dehydration or circulatory collapse producing hypovolaemia associated with conditions
such as blood loss, septicaemia, or trauma.
Renal causes can be broadly considered to be interstitial (drugs or infection), glomerular (autoimmune conditions, diabetes), tubular damage (antibiotics, drugs, toxic chemicals), or renal (vasculitis or thrombosis).
The diagnosis of acute renal failure is usually
apparent from the history. An ultrasound scan is a particularly useful diagnostic investigation and is usually combined with a plain abdominal x-ray.
1) Fluid intake is restricted to 500 mL/24 h (equivalent to insensible loss). Fluids are usually given orally.
2) Sodium intake is restricted to 20–30 mmol per day, and careful monitoring of metabolic and nutritional status is important.
3) H2 receptor antagonists and antacids are often used because of the associated incidence of upper gastrointestinal haemorrhage.
4) Dialysis is indicated if conservative measures fail to control the situation, and usually in the acute situation it is instituted via haemodialysis.
Indications for haemodialysis
Indications for haemodialysis include:
• metabolic acidosis
• fluid overload with pulmonary oedema.
Clinical course of ARF
The clinical course of acute renal failure is highly
variable depending upon the aetiology and can be considered to comprise oliguric, diuretic and postdiuretic phases.
1) The oliguric phase usually starts early on but may be prolonged for up to three months or more.
2) A diuresis can occur at any time and is often a sign that recovery is occurring. It is important to maintain vigilance particularly during this time because of the potential for loss of fluid and electrolytes.
3) Renal function may continue to improve for up to a year, but distal tubular function is often permanently impaired, although this may be difficult to determine clinically.
Chronic renal failure
1) The commonest causes of chronic renal failure include diabetes mellitus, glomerulonephritis, chronic pyelonephritis, hypertension, connective tissue diseases, and polycystic kidneys.
2) Other causes include renal calculi, vesicoureteric
refl ux, bladder outlet obstruction and myeloma and
Patients with chronic renal failure usually have
polyuria with loss of normal concentrating ability.
Nocturia is often said to be an early sign and the
urine contains protein with granular casts and white
Pathology in CRF
1) Sodium is gradually retained in chronic renal failure, albeit the serum sodium level is a poor
reflection of this.
2) In end stage chronic renal failure potassium levels may rise and acidosis is inevitable due to decreased ammonium ion excretion and decreased excretion of buffer phosphate, the urine pH usually being less than 5.
3) Since calcium levels may fall, secondary hyperparathyroidism is not uncommon and osteomalacia may occur which is sometimes vitamin D resistant.
4) Magnesium levels may rise because of the inability to excrete a magnesium load. Characteristically the urea, uric acid and creatinine levels rise. Serum creatinine levels are a useful way of monitoring chronic renal failure. Anaemia occurs as a consequence of chronic renal failure, which is usually normochromic and normocytic and is likely to be due to marrow suppression with reduced red cell survival.
Investigation of CRF
1) Appropriate investigation of patients with chronic
renal failure in addition to biochemical investigations includes ultrasound scan of the upper tracts and a check on postvoiding residual urine.
2) It must be remembered that up to a third of patients with chronic retention of urine present with chronic renal failure.
3) The aim of conservative treatment is to delay the progressive deterioration of renal function and its consequences.
Treatment of CRF
1) Fluid intake should be controlled to produce
a urine output of approximately 1 L/24 h, blood pressure is controlled by the use of antihypertensive drugs, and cardiac failure is treated using standard measures.
2) The anaemia of chronic renal failure responds
well to the use of exogenous erythropoietin and may be treated by transfusion, although this is not usually used unless the patients are severely symptomatic.
3) In some patients protein intake is restricted to 40 g/24 h in order to reduce the production of nitrogenous waste products.
Dialysis in CRF
When conservative measures fail, dialysis is instituted, and this is usually in patients in whom the serum creatinine has risen above 1000 mmol/L or if the creatinine clearance is less than 1 mL/min. The options for dialysis lie between haemodialysis and peritoneal dialysis.
In brief, the principle of haemodialysis is to allow selective diffusion of molecules below a certain size from the peripheral blood into the dialysis fluid.
Haemodialysis uses an artificial semipermeable membrane which is disposable.
In contrast, peritoneal dialysis is less efficient and uses the peritoneum as a membrane, and is more commonly complicated by infective sequelae. However, it is particularly useful in the home situation and is cheaper than haemodialysis.
Wherever possible, renal transplantation should be carried out.
Lower UTI assessment
Urodynamic assessment of the urinary tract relates to the study of pressure and fl ow relationships within the urinary tract.
Urodynamic tests should be considered to represent a hierarchy of investigations:
• Fluid volume chart
• Flow rate
• Ultrasound post-void residual volume estimation
• Urodynamic assessment; and
• Video urodynamic assessment.
Failure to store urine
This can result from overactivity of the bladder, underactivity of the sphincteric outlet mechanism, or lastly because of an oversensitivity of the lower urinary tract.
In practical terms the principal pharmacotherapeutic
agents used for bladder overactivity are anticholinergics.
The smooth muscle relaxant Urispas (flavoxate) has not been shown to be effective in placebo-controlled trials and cannot, therefore, be recommended for use.
An additional therapeutic avenue which can be utilised is to stop urine production, using an ADH analogue, which is used for patients with severe bladder overactivity and in particular, nocturia
due to nocturnal polyuria.
Iatrogenic causes of failure to store: Anticholinergics
Failure to store (detrusor overactivity)
Iatrogenic causes of failure to store: Desmopressin (DDAVP)
Failure to empty (bladder outflow obstruction)
Iatrogenic causes of failure to store: Alpha 1-adrenoceptor antagonists
Iatrogenic causes of failure to store: 5alpha-reductase inhibitors
Failure to empty
This can be due to bladder underactivity or obstruction to the outlet.
Pharmacotherapy directed at bladder underactivity,
including the use of muscarinic agonists, is not effective, has a number of side effects, and is not routinely used in contemporary urological practice.
Conversely, alpha 1-adrenoceptor antagonists which act to relax the muscle in the outlet to the bladder both of the prostate and the bladder neck are efficacious in the management of prostatic obstruction.
Recently, the use of 5alpha-reductase inhibitors has shown to be benefi cial in the management of bladder outflow obstruction due to their effect of shrinking the prostate gland by inhibition of conversion of testosterone to di-hydrotestosterone, its more active form. These agents can be used alone, or in combination with alpha1-adrenoceptor antagonists. They are most effective in larger prostate glands (>40 cm3). A number of other agents are marketed for the management
of these disorders but have not been found to
be particularly efficacious.
Side effects of active agents
All autonomically active agents do have side effects, and anticholinergics produce a dry mouth, heartburn and can cause visual disturbances. Conversely, alpha 1-adrenoceptor antagonists can reduce the blood pressure and produce dizziness, drowsiness and other non-specifi c effects.
Patients should be counselled regarding these side effects before therapy is commenced. As a general rule drugs are titrated against efficacy and side effects. alpha 1A-adrenoceptor antagonists
are more specifi c for the smooth muscle of the bladder neck and prostate, and have been shown to have less systemic side-effects, and are increasingly favoured.
Erectile dysfunction affecting the penis in the male and the clitoris in the female is the subject of considerable interest at present.
The innervation of these structures is provided by the nervi erigentes (S2–S4). Nitric oxide has been identifi ed as a relaxant agent within the erectile
structures. Unfortunately nitric oxide agonists are
too toxic for use in routine clinical practice, and this
forms the basis of treatment with the new phosphodiesterase-5 inhibitors such as sildanefil, vardenafil and tadalafil which act to prevent the breakdown of cyclic GMP, which is a substance produced via the nitric oxide pathway.
Other pharmacotherapeutic agents used to treat erectile dysfunction act as smooth muscle
relaxants and include agents such as papaverine
or prostaglandins (typically alprostadil) which can be injected into the corpora cavernosa. More recent studies have investigated the intra-urethral administration of such agents, and in addition some interest has been aroused by the use of oral !1-adrenoceptor antagonists which do have some effi cacy in this area.
Failing efficacy with drug therapy then either a vacuum artifi cial erection device can be utilised or alternatively prostheses can be inserted into the penis.
Two-thirds of injuries to the kidney occur as a consequence of blunt trauma and result from a crush injury between the anterior ends of the lower ribs and the upper lumbar spine. There is often associated bony injury and bruising in the flank.
After initial clinical assessment, whilst an ultrasound scan can be helpful it is recommended that a contrast study should be carried out. CT scanning is the gold standard, and has superceded the IVU in the acute situation.
Typically, three-phase contrast-enhanced scans are performed to examine the gross anatomy, vascular anatomy, extent of haematoma (if present), uptake of contrast by the kidney and the presence of any extravasation of contrast from the collecting system after a short time delay.
Management of renal injury
The main aim of management is to preserve renal
function and minimise blood loss. In the majority of
instances renal trauma is managed by bed rest, appropriate analgesia and careful sequential review, usually by ultrasound scan. Antibiotics are given as a routine to prevent the development of associated infection, particularly if there is any evidence of extravasation.
Such a conservative policy results in only a small proportion of patients coming to operation. If surgical exploration is required in the context of blunt trauma to the kidney then the majority of cases do result in either total or partial nephrectomy.
Innovative work from the USA, where penetrating injuries are more common, has resulted in a much higher level of renal preservation. In such circumstances preoperative evaluation of
the situation by arteriography is often carried out.
Injuries to the ureter are uncommon as a consequence of external trauma; they can occur in the context of penetrating injuries, but the commonest cause is iatrogenic during the course of intra-abdominal surgery, usually pelvic surgery.
The majority of ureteric injuries occur in the lower third of the ureter, and it has been reported that ureteric injury complicates up to 0.5% of routine
hysterectomies, with a much higher incidence for radical hysterectomies (up to 5%). The diagnosis of injury to the ureter is diffi cult in the immediate postoperative period unless the diagnosis is suspected.
Any patient who develops loin discomfort or a persistent pyrexia, or indeed any evidence of per vaginam urinary leakage, should be investigated fully, initially by ultrasound scan, but if any doubt exists as to potential diagnosis then an IVU should be carried out even in the presence of an apparently normal ultrasound scan.
The bladder is very fl exible in being able to alter its
shape and size radically to accommodate a large volume of urine. Rupture of the bladder tends to occur either in the context of patients who have undergone previous surgery to the bladder or more commonly in patients with an overdistended bladder, often related to excessive alcohol consumption. Two types of bladder rupture are
recognised: intraperitoneal and extraperitoneal.
intraperitoneal and extraperitoneal bladder injury
The diagnosis may be suspected on ultrasound scan and can be confi rmed by the passage
of contrast into the bladder, when extravasation
will be seen. Intraperitoneal rupture usually occurs in the context of compression by an external force such as a seat belt or as a consequence of a penetrating suprapubic injury piercing a full bladder.
Iatrogenic intraperitoneal rupture can occur at the time of endoscopic surgery but is usually recognised at an early stage by the surgeon. Extraperitoneal rupture of the bladder is usually associated with fractures of the pelvis, with a
reported occurrence in up to 10% of cases.
Intraperitoneal extravasation, if it is of signifi cant
degree, should be dealt with by open surgical repair and appropriate drainage. Extraperitoneal rupture will often settle with catheter drainage of the bladder. It is important to diagnose bladder ruptures since, if untreated, major perforations are associated with a high mortality.
Urethral injuries by themselves are never life threatening except as a consequence of their close association with pelvic fractures and multiple organ injuries.
Because of this close relationship to trauma, it is of no surprise that the highest incidence of urethral injuries is in adults 15–25 years of age. There is also a significant number that occur iatrogenically. Urethral injuries can range from a mild contusion with preservation of epithelial continuity, to a partial tear of the urethral epithelium or a full urethral transection and disruption.
They can also be classified by site into anterior
urethral injuries and posterior urethral injuries – which is probably the best way to consider them, as both sites are exposed to different mechanisms of injury.
Anterior urethral injuries
Injuries to the anterior urethra occur with a frequency one-third that of those to the posterior urethra
Posterior urethral strictures
Unfortunately, the term posterior urethral stricture is
still widely used to include both simple sphincter strictures and subprostatic pelvic fracture urethral distraction defects (PFUDDs). This is confusing because they, and the principles of their surgical resolution, are entirely different. Logically, the term urethral stricture should be used to indicate a narrowing of urethral continuity, not a gap.
Simple continuity strictures of the membraneous urethra are commonly the result of an internal urethral injury (prostatic surgery, instrumentation,
indwelling catheters, or tumour invasion); they are best referred to as sphincter-strictures because
this emphasises that, although the function is generally impaired to a variable extent, the distal urethral sphincter mechanism has not been destroyed.
The primary aim of the treatment of a sphincter stricture must be the preservation of the residual distal sphincteric function, just as the primary aim of the management of a PFUDD is the preservation or functional reconstruction of the residual sphincter mechanism at the bladder neck only, because in all but the most minimal lesions the function of the intramural distal urethral sphincter is destroyed by the subprostatic urethral
rupture through its mechanism.
The posterior urethra has a close relationship with
the bony pelvis and is often associated with serious
injury as a result of a severe external force to the pelvis and lower abdomen. Of posterior urethral ruptures 65% are complete.
Aetiology of anterior urethral injuries
1. blunt trauma
— fall astride
— go-kart injuries
— kicks in the perineum
2. penetrating trauma
— stab wounds
3. sexual excess
— penile fractures
— urethral stimulation
4. constriction bands
5. iatrogenic injuries
— urethral catheters
— endoscopic instrumentations
6. postcardiac surgery
— usually as a consequence of ischaemia
Anterior urethral injuries diagnosis
Anterior urethral injuries can present with blood at
the meatus, inability to pass water, or the rapid development of a perineal urinoma or haematoma forming down a sleeve of Buck’s fascia.
Extension of the penile bruising down beyond the shaft is due to rupture of Buck’s fascia allowing the Colles fascia to act as the limiting tissue. This results in a characteristic butterfly pattern of bruising in the perineum.
Posterior urethral injuries diagnosis
The diagnosis of posterior urethral injuries requires
a high index of suspicion and should be excluded before a urinary catheter is inserted, often by an experienced person in the emergency service utilizing retrograde contrast studies. Urethral injury is to be suspected in any patient with a fracture of the pelvis. The likelihood of urethral injury increases with:
• blood at the urethral meatus;
• difficulties/inability to void;
• palpable bladder from distension, failure to void,
• bruising of the perineum
• high riding prostate, although this might be
diffi cult to appreciate in the presence of a pelvic
• Fractures involving displacement of the pubic rami
relative to the rest of the pelvis.
Urethral injuries triad
Although this classic triad of blood at the external
urethral meatus, inability to pass urine and a distended bladder is fairly indicative of urethral injuries, it must be noted that a very high lesion above the external sphincter may not produce blood at the meatus and a distended bladder may be related to a sphincter spasm as a result of pain rather than a complete urethral rupture.
Rectal examination helps to exclude a dislocated
prostate, but swelling and oedema may mask the presence of a normally positioned prostate. Rectal examination is more important as a tool to screen for rectal injuries that can be associated with pelvic fractures.
Blood on the examining fi nger is highly suggestive of such an injury.
Types of urinary tract calculi
• Calcium oxalate (75%)
• Phosphate stones (15%)
• Urate stones (5%)
• Cystine stones (2%)
• Xanthine and pyruvate stones are very rare and
arise due to inborn errors of metabolism.
Approximately 60% of calculi are radio-opaque.
Usually only urates are radiolucent, cystine stones
being faintly to moderately radio-opaque because of their sulphur content. Calculi do occur elsewhere in the lower urinary tract, both in the urethra (usually
consequent upon passage of a calculus from the ureter or bladder) and the prostate where they can be seen on x-ray in the prostatic parenchyma. Prostatic calculi are of no clinical significance.
• Calcium oxalate (75%) are usually mulberryshaped stones covered with sharp projections. They cause bleeding and are often black because of altered blood on their surface. Because of their sharp surface they often give symptoms when comparatively small. They usually occur in alkaline urine. Diets rich in rhubarb, spinach, tomatoes and strawberries may be contributory to the development of oxalate stones.
• Phosphate stones (15%) are usually composed of magnesium ammonium phosphate with calcium.
They are smooth and dirty white in colour. They
may enlarge rapidly and fi ll the calyces, taking
on their shape: i.e. staghorn calculus. They occur
in strongly alkaline urine and may be associated
with urinary tract infections with bacteria such as
Proteus which are able to break down urea to form
• Urate stones (5%) arise in acid urine and are hard,
smooth, faceted and light brown in colour.