PBL Topic 4 Case 8 Flashcards
Identify the two main steps of micturition
- Bladder fills until tension in its wall rises above a threshold
- Which elicits a nervous reflex that empties the bladder
Identify the two parts of the bladder
- Body (major part)
- Neck (funnel shaped inferior part)
What name is given to the smooth muscle of the bladder?
- Detrusor muscle
What is the main function of the detrusor muscle?
- Emptying the bladder
What is the trigone?
- Triangular shaped area
- With a smooth mucosa
- Upper two apices receive the ureters
- Lower apex opens into urethra
What is the internal urethral sphincter composed of and what is its function?
- Involuntary smooth muscle
- Prevents emptying of bladder until pressure in the body of the bladder rises above a threshold
- Controlled by micturition centre in periaqueductal gray
What is the external urethral sphincter composed of and what is its function?
- Voluntary skeletal muscle
- Used to consciously prevent urination
What is the main innervation to the bladder?
- Pelvic nerves
- Which carry sensory and motor signals
- Which connect through spinal cord through sacral plexus
- Connecting to cord segments S2-S3
What are the sensory and motor functions of nerves supplying the bladder?
- Sensory: Detects degree of stretching
- Motor: Contraction of detrusor muscle, emptying of bladder
What is the function of the pudendal nerve in the innervation of the bladder??
- Innervates the external urethral sphincter
What is the function of the sympathetic chains in the innervation of the bladder?
- Stimulate blood vessels
Which nerves do the fibres of the sympathetic chain pass through to innervate the bladder?
- Hypogastric nerves
- Connecting mainly with L2 of spinal cord
Outline the process of renal emptying of urine
- Stretching of renal calyces as they are filled with urine
- Which increases inherent pacemaker activity
- Which initiates peristaltic contractions
- Which spread to renal pelvis along ureters
- Forcing urine from the renal pelvis into the bladder
What is the role of sympathetic and parasympathetic signals to the ureters?
- Parasympathetics enhance peristaltic contractions
- Sympathetics inhibit peristaltic contractions
What is vesicoureteral reflux?
- Shorter course of ureter in the bladder
- Contraction of bladder does not fully occlude ureter
- Causing reflux and enlargement of ureters
- Increasing pressure and damaging renal calyces and medulla
What is the ureterorenal reflex?
- Blockage of ureter stimulates pain fibres
- Which causes constriction of renal arterioles
- Decreasing urine output from kidney
- To prevent excess flow into the renal pelvis with a blocked ureter
What causes a micturition reflex?
- Stretch reflex initiated in posterior urethra as bladder fills
- Which is conducted to sacral segment of cord
- And reflexively back again to bladder through parasympathetic nerve fibres
Why is the micturition reflex considered to be self-regenerative?
- Initial bladder contraction activates stretch receptors
- To cause a greater increase in sensory impulses
- Which causes a further increase in bladder contraction
- This process begins to fatigue, permitting bladder relaxation
Identify a secondary reflex caused by the micturition reflex?
- A reflex passes through pudendal nerve
- To inhibit the external urethral sphincter
- If this inhibition is more potent in the brain than the sphincter muscles urination will occur
Where are the strong facilitative and inhibitor centres for micturition located in the brain?
- Pons
How does voluntary urination occur?
- Person contracts abdominal muscle
- Which increases pressure in bladder
- Allowing extra urine to enter bladder
- Which stimulates stretch receptors
- Excites micturition reflex /reflex inhibition of external sphincter
Outline the pathophysiology of atonic bladder
- Sensory nerve fibres from bladder are destroyed
- Preventing stretch signals from bladder
- Bladder fills to capacity and overflows a few drops at a time (incontinence)
Identify two causes of atonic bladder
- Crush injury to sacral region of spinal cord
- Damage to dorsal root fibres in neurosyphilis (tabes syphilis)
Outline the pathophysiology of automatic bladder
- Loss of facilitative impulses from brain stem and cerebrum
- Micturition reflex can still occur they are just no longer controlled by brain
- Micturition reflex can be stimulated by catheterisation or stimulating the skin in the genital region
Outline the pathophysiology of uninhibited neurogenic bladder
- Damage to spinal cord and brainstem
- Which interrupts the inhibitory signals
- Which results in frequent and uncontrolled micturition
Outline the physiologic anatomy of the male sexual organs
- Sperm formed in seminiferous tubules of testes
- Sperm empties into epididymis then into ductus deferens
- Which receives seminal vesicles and empties into prostate
- Prostate empties into ejaculatory duct then into urethra
- Which receives mucus from bulbourethral glands
Identify contents of the prostatic secretions
- Calcium
- Citrate ion
- Phosphate ion
- Clotting enzyme
- Profibrinolysin
How are prostatic secretions added to the semen
- Simultaneous contraction of prostate gland and ductus deferens
What is the pH of prostatic secretions? What is the importance of this?
- Slightly alkaline
- Neutralises acid of vas deferens and vaginal secretions
- Optimum motility and fertility of sperm at pH of 6-6.5
Which hormone is responsible for growth of the prostate? Describe the growth pattern of the prostate
- Testosterone
- Remains small during childhood and begins to grow at puberty
- Reaches a stationary size by 20
- May involute after 50 with decreases testosterone production
Which cells of the testes secrete testosterone?
- Interstitial cells of Leydig
Which hormone stimulates testosterone production?
- LH
Outline the formation of testosterone from acetyl-CoA
- Cholesterol is synthesised from acetyl-CoA
- Followed by production of intermediate hormones (17-a hydroxypregnenolone and DHEA)
- And finally androstenedione
- Which is converted to testosterone
When does LH secretion begin?
- Puberty
Identify the effects of testosterone on the male sexual organs
- Maturation of reproductive organs
- Development of secondary sexual characteristics
- Thereafter, maintenance of spermatogenesis (Sertoli cells)
- Maturation of spermatozoa
Identify the anabolic effects of testosterone
- Development of musculature
- Increased bone growth
- Closure of epiphyses following puberty
Outline how testosterone exerts its effects on cells
- Testosterone converted to dihydrotestosterone
- By 5a-reductase
- Binds to testosterone receptors
- Modifies gene transcription by interacting with nuclear receptors
What is benign prostatic hyperplasia?
- Non-neoplastic enlargement of prostate gland
Outline the epidemiology of BPH
- Occurs commonly and progressively after 50
- Affects 75% of men aged 70-80 years
Outline the aetiology of BPH
- Dihydrotestosterone activates gene transcription to promote cell growth and survival
- Causing proliferation of glands and stroma of the transition zone
- Contraction of hyperplastic smooth muscle mediated by alpha-adrenergic receptor
- Role of persistent inflammation resulting in secretion of growth-promoting cytokines
Outline the morphology of BPH
- Hyperplasia in both lateral lobes
- Hyperplasia of periurethral glands projecting into bladder giving a median lobe
- Circumscribed nodules and cysts
Outline the four main pathological mechanisms in the development of symptoms in BPH
- Hyperplastic nodules compress prostatic urethra, distorting its course
- Involvement of periurethral zone interferes with sphincter mechanism
- Contraction of hyperplastic smooth muscle
- Inflammatory cell infiltration
Identify the three groups lower urinary tract symptoms (LUTS)
- Bladder sensation symptoms (increased or decreased)
- Storage symptoms (frequency, nocturia, urgency, incontinence)
- Voiding symptoms (hesitancy, poor stream, straining, dribbling)
Outline the findings of a DRE in BPH
- Asymmetrical enlargement of both lateral lobes
- Gland has a firm, rubbery consistency
Outline the pathology of hydroureter identify a complication of it
- Continued bladder obstruction causes hypertrophy and trabeculation
- Which fails and allows reflux of urine
- Which causes dilation of ureters
- Results in dilation of renal pelvises (bilateral hydronephrosis)
Why does cystitis occur in BPH? What are the symptoms
- Residual urine causes cystitis due to coliform organisms
- With dysuria, haematuria and increased frequency
Outline a complication of cystitis
- Ascending infection causes pyelonephritis with impaired renal function
- Which can result in the formation of calculi and septicaemia
Identify the investigations in the diagnosis of BPH
- Scoring of symptoms using IPPS
- Microbiological exam for evidence of infection
- U+E for kidney function
- Ultrasonography indicated enlarged prostate and obstruction
- Elevated prostate specific antigen to rule out cancer
Outline the management of BPH
- Pharmacological treatments e.g. finasteride and tamsulosin, anti-inflammatory drugs and antibiotics
- Urethral catheter drainage in acute retention
- Surgery (transurethral resection of hyperplastic prostate tissue) where catheterisation is impossible
Outline the mechanism of action of finasteride
- Inhibits 5a reductase
- Reduced dihydrotestosterone formation
Outline the mechanism of action of tamsulosin
- a1A receptor antagonist
- Relaxation of smooth muscle of bladder neck
- Inhibition of hypertrophy
Why is tamsulosin preferred over other alpha receptor antagonists
- Selective for bladder
- Causes less hypertension
Identify an adverse effect of tamsulosin
- Failure of ejaculation
Identify a difference in the indication of finasteride and tamsulosin
- Finasteride indicated when prostate > 40 cm3
- Tamsulosin indicated when prostate < 40 cm3
Outline the epidemiology of prostate cancer
- Second leading cause of male death from malignancy in Europe/USA
- Incidence is 40,000, with 10,000 deaths annually
- Peak incidence between 65-75
- Rare below 50
Which zone do most prostate tumours arise?
- Peripheral zone
Why can prostate carcinoma arise after transurethral resection?
- This operation does not remove the peripheral zone
What type of tumour are most prostate cancers?
- Adenocarcinoma
- Often described as microacinar
Identify two rare subtypes of prostate cancer
- Small cell carcinoma
- Large duct carcinoma
Identify a grading system used for prostate cancer
- Gleason grading system
Identify five Gleason patterns
- GP1: Not carcinoma
- GP2: Small, circumscribed masses of regular glands
- GP3: Separate gland profiles that infiltrate into normal glands
- GP4: Fused glands / cribiform structures
- GP5: Undifferentiated, central necrosis
How is the Gleason Grading system used?
- Gives a combined score using most dominant pattern and next most frequent pattern
- E.g. GP5 +GP4 = GP9
- Doubled when only one pattern is seen
- E.g. GP3 + GP3 = GP6
What is a prostatic intraepithelial neoplasia
- Common precursor of carcinoma
- Which composes of malignant cells
- That are confined within ductal system
- With no invasion of stroma
Identify 3 modes of spread of prostate cancer
- Direct invasion into seminal vesicles, bladder
- VIa lymphatics to sacral, iliac or para-aortic nodes
- Via blood to bone (osteosclerotic), lungs and liver
Identify the four main clinical features of prostate cancer
- Urinary symptoms e.g. changes in frequency
- Rectal exam revealing hard craggy prostate
- Bone metastases e.g localised back pain
- Lymphadenopathy due to metastasis
What is prostate specific antigen?
- Glycoprotein produced by prostate epithelium
- Which has a role in liquefaction of semen
- Increases with age
- Elevated serum levels in prostatic cancer
Identify three common ways used to diagnose prostate cancer
- DRE
- PSA
- Transrectal ultrasound-guided needle biopsy
Outline the management of prostate cancer
- Early confined tumour removed by radical prostatectomy
- Endocrine treatment e.g. orchidectomy, androgen suppressing drugs
- Chemotherapy where endocrine therapy fails
- Analgesia or radiotherapy for relief of back pain
Identify two androgen receptor antagonists and briefly how they work
- Flutamide
- Abiraterone
- Which inhibit CYP17 which is necessary for androgen production
Identify two GnRH agonists and briefly how they work
- Goserelin
- Leuprorelin
- Which occupy pituitary receptors, preventing them from responding to GnRH pulses which normally stimulate LH and FSH
Identify one adverse effect of GnRH agonists
- Cause initial rise in LH and testosterone
- Which require an anti-androgen e.g. flutamide
Outline the prognosis of prostate cancer
- Life expectancy of an incidental finding of focal carcinoma is normal
- 10 year survival rate is 70% in more substantial tumours
- 10 year survival rate is 10% if metastases are present
Outline the uses of ultrasound in renal imaging
- Renal size
- Dilatation
- Tumours and cysts
- Bladder emptying
What is the resistivity index?
- Ratio of peak systolic and diastolic velocities
- Influenced by the resistance to flow through these vessels.
- Using doppler techniques
Identify conditions that result in an elevated resistivity index
- Acute glomerulonephritis
- Rejection of renal transplant
Identify 4 limitations of ultrasound scanning
- Poor visualisation of renal pelvis, calyces and ureters
- May miss renal and ureteric calculi
- It is operator dependent
- It is often less clear in obese patients
What does pyelography involve? Describe the two types
- Injection of contrast medium into the collecting system
- Allows for drainage and stent insertion in obstruction
- Anterograde: insertion of fine needle into pelvicalyceal system under ultrasound
- Retrograde: insertion of catheters into ureteric orifices at cystoscopy.
What is the first line investigation in ureteric colic?
- CT scan (Ultrasound if Woman)
Identify an advantage and a disadvantage of CT scanning
- It gives clear definition regardless of obesity
- Radiation and contrast nephrotoxicity
Identify two other uses of CT scanning
- Characterising cysts and masses
- Useful in trauma, haemorrhage and stenosis
Identify 3 uses of MRI scanning
- Characterise renal masses
- Staging of renal, prostate and bladder cancers
- Angiography with gadolinium
Why is it advised not to use gadolinium in patients with renal insufficiency
- Development of nephrogenic systemic fibrosis
How is renal biopsy performed?
- Transcutaneously under ultrasound
- Which is then examined by histological staining, microscopy or immunofluorescence
Outline the uses of renal biopsy
- Nephrotic and nephritic syndromes
- Acute and chronic kidney disease
- Haematuria
Identify 3 contraindications to renal biopsy
- Disordered coagulation or thrombocytopenia
- Uncontrolled hypertension
- Kidneys that are less than 60% the predicted size
Identify four complications of renal biopsy
- Mild pain
- Bleeding into urine
- Bleeding around the kidney
- Arteriovenous fistula
Identify 7 causes of urinary tract obstruction
- Urinary calculi
- Tumours e.g. prostatic carcinoma
- Inflammation e.g. urethritis
- Benign prostatic hypertrophy
- Uterine prolapse
- Congenital defects e.g. meatal stenosis
Outline how urinary tract obstruction causes atrophy
- Increase in pressure proximal to obstruction
- Which is transmitted to collecting ducts, with loss of tubular function
- Increase interstitial pressure reduces medullary blood flow
Why is there an increased risk of UTIs and urolithiasis in urinary tract obstruction?
- Stagnant urine predisposes to bacterial infections
- And development of magnesium ammonium phosphate stones
Identify symptoms of an upper tract obstruction
- Loin pain
- Anuria suggests complete bilateral obstruction
- Polyuria due to impairment of renal tubular concentrating capacity
- Malaise, fever, septicaemia due to infection
Identify the symptoms of bladder outflow obstruction
- Hesitancy, narrowing and diminished force of urinary stream
- Terminal dribbling
- Sense of incomplete bladder emptying.
- Infection suggested by increased frequency and urgency, urge incontinence, dysuria and the passage of cloudy smelly urine.
Outline the findings on examination in urinary tract obstruction?
- Palpable hydronephrotic kidney (owing to dilatation of renal pelvis, calyces and papillae)
- Enlarged bladder can be felt or percussed
Why is it important to examine the genitalia in suspected urinary tract obstruction?
- Malignancy is a cause of obstruction
What do
routine blood and biochemical investigations show in urinary tract obstruction?
- Raised serum urea or creatinine
- Hyperkalaemia
- Anaemia of chronic disease
- Blood in urine
What do plain x-rays show in urinary tract obstruction?
- Stones
- Calcification
Why is ultrasonography used in urinary tract obstruction?
- Upper tract dilatation
What are the three aims of treatment in urinary tract obstruction?
- Relieve obstruction e.g. external drainage of urine by nephrostomy,
- Treating the underlying cause
- Preventing and treating infection
Outline factors that affect prognosis in urinary tract obstruction?
- The site of obstruction
- Whether obstruction is partial or complete
- Duration of obstruction
- Whether or not infection occurs
What is urolithiasis?
- Development of calculi (stones)
- Which may occur at any level of urinary tract
- But most frequently within the kidney
Identify the four most common types of stones and what each type is associated with
- Calcium stones: hypercalciuria
- Uric stones: hyperuricaemia
- Magnesium ammonium phosphate: bacterial infections e..g Proteus
- Cysteine stones: cystinuria
Outline the clinical features of urolithiasis
- Infections
- Haematuria due to mucosal injury
- Pain worsened by measures that increase urine volume
- Pain worsened by physical exertion owing to movement of calculi
What is ureteric colic and what are the symptoms?
- Stone enters ureter causing obstruction or spasm during its passage
- Abrupt pain that starts and stops
- From flank to iliac fossa and testes or labium (loin to groin!)
- Associated with vomiting, sweating, pallor, haematuria
What are the investigations in urolithiasis?
- Mid stream specimen for urine culture
- Serum urea, electrolytes, creatinine, calcium levels
- Plain x-ray
- CT-KUB
Outline the treatments of urolithiasis
- Analgesia e.g. diclofenac intravenously
- Small stones pass spontaneously though alpha blockers (tamsulosin) facilitate spontaneous expulsion
- Large stones removed by extracorporeal shock wave lithotripsy (ESWL), YAG laser of percutaneous nephrolithotomy
Identify the two routes of infection in acute pyelonephritis
- Haematogenous spread secondary to septicaemia
- Ascending urinary tract infection
Identify the mechanism by which lower urinary tract infections cause acute pyelonephritis
- Vesicoureteric reflux
- Due to congenital abnormality
- Or bladder outflow obstruction
Why are urinary tract infections more common in women?
- Short urethra
- Urethral trauma associated with sexual intercourse
Identify two other common causes of urinary tract infection
- Pregnancy
- Diabetes mellitus
Ascending infection is usually with which type of bacteria?
- Enteric gram negative bacilli
- Such as E.coli and enterobacter
Identify three causes of pyelonephritis due to haematogenous spread
- Endocarditis
- Osteomyelitis
- Soft tissue abscesses
Identify the clinical features of acute pyelonephritis
- Fever and malaise
- Loin pain and tenderness
- LUTS such as frequency and dysuria
Identify the histological findings in acute pyelonephritis
- Large number of neutrophils (pyuria) and neutrophil casts
What is the treatment for acute pyelonephritis?
- Amoxicillin
- Co-amoxiclav or ciprofloxacin for resistant organisms
What is chronic pyelonephritis
- Renal scarring and chronic inflammation
- Secondary to untreated vesicoureteric reflux or urinary tract obstruction
What are the clinical features of chronic pyelonephritis?
- Asymptomatic
- Followed by signs and symptoms of CKD
- Such as malaise, loss of appetite, insomnia, nocturia and polyuria
What are the morphological findings of chronic pyelonephritis?
- Renal fibrosis with a segmental distribution
- Dilated and distorted calyces
- Casts of uromodulin (glycoprotein produced by tubular epithelium)
What is xanthogranulomatous pyelonephritis?
- Variant of chronic pyelonephritis
- With large collections of foamy macrophages appearing as yellow nodules
- Associated with proteus infections and obstruction
What is tuberculous pyelonephritis?
- Caused by haematogenous spread from lungs
- Characterised by granulomatous inflammation.
Which type of pre-operative fear is related to a decrease in post-operative stress?
- Moderate pre-operative fear
- It is associated with defence mechanisms, coping strategies, seeking out relevant information
- Which all increase confidence in the outcome
Identify the four types of information that could be used to affect the outcome of recovery from surgery
- Sensory information: dealing with feelings and reflecting on them
- Procedural information: learning about the actual intervention
- Coping skills information: teaching possible coping strategies
- Behavioural instruction: how to behave afterwards (e.g. relaxing)
Outline the importance of pre-operative information
- Reduces anxiety, pain rating, length of hospitalisation and analgesic intake
- As it allows patient to mentally rehearse their anticipated worries
- So worries become predictable
What is consequentialism?
- Morally right action is one that gives the best consequences
- Action taken is justified as the consequences are for the greater good
Identify three types of consequentialism
- Utilitarianism: promotes happiness for the greatest number of people
- Egoism: best course of action is what is best for the individual
- Altruism: doing what is best for other’s wellbeing
Identify two weaknesses of consequentialism
- Hard to know what consequences will be
- Some actions are self-evidently wrong even if consequences are good
What is deontology?
- Fundamental rules to be followed
- One must act from duty
- Certain acts are wrong regardless of consequences
Identify a weakness of deontology
-Ignores the consequences which may not all be good
What is virtue ethics?
- Virtues are characteristics that promote human flourishing
- They include comparison, patience, kindness and fidelity
Identify two weaknesses of virtue ethics
- Centres on the person and includes the whole of a person’s life
- Does not provide clear guidance, there are no general agreement on what the virtues are, virtues are relative to culture
What is principalism?
- Focus on four ethical principles e.g. autonomy, beneficence, non-maleficences and justice
What is dynamism?
- Claims all situations are dynamic
- Emphasises that a decision taken at one time may not be appropriate at a later stage
What is sensitivity?
- Proportion of people with the disease correctly identified by the test.
- Probability that the test result will be positive when the disease is present
- True positive rate
What is specificity?
- Proportion of people without the disease correctly identified by the test;
- Probability that a test result will be negative when the disease is not present
- True negative rate.
How is the sensitivity of a test calculated?
- TP / TP + FN
How is the false negative rate calculated?
- FN / TP + FN
- 1 - Sensitivity
How is the specificity of a test calculated?
- TN / FP + TN
How is the false positive rate calculated?
- FP / FP + TN
- 1 - Specificity
What is a positive predictive value?
- Probability that the disease is present when the test is positive
How is the positive predictive value calculated?
- TP / TP + FP
What is a negative predictive value?
- Probability that the disease is not present when the test is negative
How is the negative predictive value calculated?
- TN / TN + FN
What is meant be trade off between sensitivity and specificity?
- Changing the cut off point for a positive outcome
- Will either increase specificity and decrease sensitivity
- Or vice versa
What name is given to a graph that presents the sensitivity and specificity?
- Receiver Operating Characteristics Curve
How can the accuracy of a diagnostic test be measured using an ROC curve?
- An area of 1 represents a perfect test, where sensitivity and specificity are both 1
- An area of 0.5 represents a worthless test, where sensitivity and specificity are both 0.5
How does the shape of the curve represent accuracy of a diagnostic test?
- An area of 0.5 would be found with a diagonal line
- The closer the curve follows the left and top border, the more accurate the test
What does the IPSS take into account?
- Severity of LUTS symptoms
- And QALY measure
