Urinary Tract Function & Infection

Question 1

What is the definition of the lower urinary tract?

Answer 1

Lower urinary tract definition – bladder and urethra

In males this refers to the anterior urethra (penile urethra and bulbar urethra), posterior urethra (membranous and prostatic urethra) and the bladder itself

Question 2

What is the definition of the upper urinary tract?

Answer 2

Upper urinary tract – bilateral ureters and bilateral renal collecting systems

Question 3

What structures protect the lower urinary tract?

Answer 3

LUT is protected by fascial layers and some protection from bone (pubic rami anteriorly and posteriorly by the iliac wings)

Question 4

How does the detrusor muscle in the bladder differ between males and females?

Answer 4

Thicker detrusor muscle in males – males need to work hard to overcome the resistance provided by the prostate gland

Question 5

What are the roles of the urothelium, lamina propria and detrusor muscle in the wall of the bladder?

Answer 5

Different layers with different roles

Urothelium – barrier function and afferent signaling

Lamina propria – functional center that coordinates the signals from the urothelium and detrusor muscle – blood vessels, nerves and myofibroblasts pass through here

Detrusor muscle stroma – smooth muscle arranged in bundles, functional syncytium (cells fused), stroma – consists of collagen and elastin, innervation of muscle by the postganglionic parasympathetic system

Question 6

Why do tight junctions between epithelial cells in the bladder play an important role?

Answer 6

Apical membrane with tight junctions – important for signaling for bladder filling/stretching – signals relayed onwards to allow for bladder voiding

Question 7

What are the normal functions of the bladder?

Answer 7

Three main roles
- Compliant reservoir for urine
- Barrier function (GAG layer/tight junctions) - prevent leakage of urine (but not truly waterproof) – damage to the urothelium plays a role in disease
- Volitional voiding – muscular function to remove urine

Question 8

How does the bladder pressure stay constant despite increases in volume?

Answer 8

Bladder pressure remains constant despite increase in volume

Bladder is highly compliant due to visco-elastic properties (elastin/collagen; detrusor relaxation
without change in tension)

Question 9

How is the level of bladder filling detected?

Answer 9

Bladder filling stretch sensors detect increase in wall tension

Afferent neurons send signals to the dorsal horn of the sacral spinal cord, which relay signals to the higher centers and brainstem – real time data – allows for control of bladder

Question 10

From a neurological perspective, how is urine voiding controlled?

Answer 10

Urine voiding is controlled by the spino-bulbar reflex

But it is modulated by the pontine micturition centre (Barrington’s nucleus) in the brain (pons) - allows for voiding to occur on socially acceptable times.

And further processing taking place in the Onuf’s Nucleus (sacral level - S2, S3 and S4)

Question 11

When is normal and uncomfortable bladder fullness detected?

Answer 11

Bladder fullness is detected at 250ml and uncomfortable at 500ml

Question 12

What coordinated action between the baldder and sphincters for voiding to take place?

Answer 12

During voiding – coordinated action of detrusor contraction and urethral sphincter relaxation – allows urine to enter the posterior urethra allowing voiding to occur

Question 13

What is the positive feedback loop that helps drive micturition?

Answer 13

During voiding itself – positive feedback loop

Detrusor contracts – wall tension rises – afferent signals to PMC – processes these – strengthens contractions with efferent signals

Question 14

What are the two nerves responsible for driving detrusor contraction and sphincter relaxation?

Answer 14

Pelvic nerves - detrusor

Pudendal nerves - sphincter relaxation.

Question 15

Explain what this diagram is showing.

Answer 15

Normal neurophysiology

Bladder filing - Afferent signals from stretch receptors sent to the sacral spinal cord – sent up to the higher centers (pons and other areas) – sends efferent signals back down and if the bladder is sufficiently full this will lead to volitional voiding – leads to coordinated detrusor muscle contraction and sphincter relaxation via the pelvic nerves and the pudendal nerves

Overall reflex arc is under control of higher centers - mainly the PMC

Bladder is subject to facilitation (contraction of detrusor and relaxation of sphincter when the bladder is less than full) and inhibition (postponement of voiding) – external factors

Question 16

What are some neurotransmitters/molecules involved in regulating bladder activity?

Answer 16

Numerous neurotransmitters involved
- Excitatory - Cholinergic + Role of nitric oxide in the relaxation of the bladder neck and external urethral sphincter
- Inhibitory – GABA and glycine

Question 17

What happens to the neurological control of bladder function if we get a spinal cord injury?

Answer 17

Spinal bulbar reflex arc is modulated by higher centers – spinal cord injury results in loss of central inhibition – results in control of voiding by the spino-bulbar-arc (parasympathetic nerves and pudendal nerves)

Question 18

How does damage to the suprapontine, spinal and sacral regions influence bladder function?

Answer 18

How a patient presents depends on the level where the injury has taken place

Suprapontine – storage symptoms – experience urgency and frequency to pass urine, they pass urine completely (no residual) but have detrusor overactivity

Spinal – both storage and voiding (poor intermittent urinary flow) + PVR (post-voiding residual urine) is raised – don’t empty to completion, detrusor overactivity and dyscoordination between detrusor muscle and the sphincters

Sacral – voiding symptoms, PVR is raised and urodynamics – hypocontractile or acontractile detrusor

Question 19

On average, how frequently do people urinate and how much do they urinate (volume) when they do go?

Answer 19

Bladder responsible for STORAGE of urine

When the bladder contains c. 300mls (and it is socially convenient) VOIDING is initiated.

Normal voiding pattern - 300-400mls per void, 4-5 per day (less than 7) - depending on input

No urgency or incontinence.

Question 20

What two ways do we use to collect data on someone’s bladder function?

Answer 20

Patients coming to clinic – void to frequently or at night

In this case we use a volume and frequency chart or a bladder diary to understand what’s happening in more detail

Question 21

What is a frequency/volume chart?

Answer 21

Frequency and volume chart – frequency and volume – gives us information on frequency, functional capacity and nocturia (when) – but no info on intake!

Question 22

What is a bladder diary?

Answer 22

Bladder diary – monitors inputs (volume ingested, type of fluid and when) as well as outputs (frequency, functional capacity and voiding at night)

Can pick up on important information such as…
* Drinking at night – resulting in nocturnal diuresis
* Wet UI episodes – incontinence episodes

Question 23

What are storage lower urinary tract symptoms?

Answer 23

STORAGE LUTS:
1. Urgency
2. Frequency
3. Nocturia
4. UI: urinary incontinence

Question 24

What are voiding lower urinary tract symptoms?

Answer 24

VOIDING LUTS:
1. Hesitancy
2. Poor flow
3. Intermittency
4. Terminal dribbling

Question 25

What might be causing storage LUTs (increased frequency, urgency and nocturia)?

Answer 25

Storage LUTS – frequency urgency and nocturia Reflects... 1. Increased urinary production (excess urine output or fluid intake) 2. Decreased capacity - reduced compliance or functional capacity - results from irritation (bladder stones or tumour) or neurogenic bladder (MS - early emptying)

Question 26

What is normal nocturnal frequency? What are reasons why it might increase?

Answer 26

Nocturia – nocturnal frequency - less than 2x night Reasons - ageing bladder, BOO (bladder outflow obstruction), bladders with reduced compliance (expansion) and dietary habits

Question 27

Why do we see increase nocturnal urination as we age?

Answer 27

Effect of ageing – renal concentrating ability decreases (e.g. less salts reabsorbed) which increases urine output Patients with peripheral ankle oedema (cardiac/renal failure - more common with age) - we see increased renal blood flow at night when patients are laying flat in turn increasing urine production Nocturia is important cause it can increase the risk of falls

Question 28

What is the definition of nocturnal polyuria?

Answer 28

Nocturnal polyuria – production of more than one third of 24-hour urine output between midnight and 8am

Question 29

What are the voiding LUT symptoms? What is it normally caused by?

Answer 29

Voiding symptoms: 1. Hesitancy - Delay in start of micturition 2. Intermittency – start/stop - prostatic enlargement 3. Post-void dribble - due to release of urine retained in the bulbar/prostatic urethra 4. Straining - use of abdominal muscle for voiding Cause – decrease force of micturition usually secondary to bladder outlet obstruction (BOO) or urethral structure (plumbing) but may also occur with underactive/hypo-contractile bladder (spinal cord injury – pump)

Question 30

What is the definition of incontinence?

Answer 30

Defined as ‘involuntary loss of urine that is a social or hygienic problem and is objectively demonstrable’

Question 31

What are the two types of incontinence?

Answer 31

Urge urinary inctontinence (UUI) – associated with a strong desire to void detrusor contraction Stress urinary incontenince (SUI)– involuntary loss of urine when intra-abdominal pressure rises without detrusor contraction – coughing, sneezing, laughing, straining or exerting

Question 32

How are urinary symptoms assessed?

Answer 32

History - frequency volume chart or bladder diary Examination – rectal examination to examine prostate and rectal tone (spinal injury) Urinalysis Special investigations * International Prostate Symptom Score (IPSS) - 7 questions. * Flow rate & PVR (post-void residual vol) * Urodynamics

Question 33

Whats a uroflowmeter?

Answer 33

UroFlowMeter looks at... Look at voiding volume Maximal urinary flow rate Voiding time Bladder scan can be used to look for residual volume – over 200ml is significant

Question 34

What is urodynamic assessment?

Answer 34

Determine underlying cause of the symptoms – used in patients with complex voiding patterns or complex neurological abnormalities or young patients with severe symptoms Place pressure transducers - bladder and rectum – pressure from bladder and rectum measured during filling and voiding + patient is asked to cough periodically to check that transducers are working and checking for stress incontinence By subtracting rectal from abdominal pressure we can measure detrusor activity – **pressure generated by the bladder itself **

Question 35

Explain the different parts of this normal urodynamics trace.

Answer 35

Normal looking urodynamics trace Equipment - urethral catheter, intra-vesicle pressure transducer and pressure transducer in the rectum Trace divided into the Filling and voiding phase Intravesical pressure – abdominal = detrusor pressure **Filling phase** – saline solution is introduced into the bladder at a constant rate (blue trace at the bottom) * Detrusor pressure is low – while filling – indicates that the bladder has a compliant bladder * When they cough (shown by abdominal increases in pressure) there is no urinary outflow (no stress urinary incontinence) * No detrusor activity in the filling phase (no overactivity present) * **Voiding phase** – remove urethral catheter + transducers remain + patient is asked to void * Rise in intravesical and detrusor pressure – resulting in urinary outflow – normal function in this case

Question 36

What does the following urodynamics trace show? What would the patient benefit from?

Answer 36

Patient with unstable bladder – detrusor overactivity with detrusor overactivity incontinence – benefit from anti-muscarinic therapy or botox therapy for the bladder. Filling phase – see spontaneous detrusor pressure in the filling phase – evidence of overactivity Coughing – rise in abdominal pressure – no urinary flow present – no stress incontinence Voiding phase – rise in intravesical pressure – results in urinary flow – no evidence of obstruction of flow

Question 37

What does the following urodynamics trace show?

Answer 37

Patient with stress urinary incontinence with a normal compliance bladder - coughing (abdominal pressure rises) coincides with urinary outflow – stress incontinence

Question 38

What's going on in the followign urodynamics trace?

Answer 38

Bladder outlet obstruction * No unstable contractions during filling * No leak whilst coughing during filling * Very high pressure and low flow during voiding

Question 39

What are the symptoms of outflow obstruction? Why is obstruciton problematic in the long run?

Answer 39

If though obstruction is the problem - storage symptoms may come first then followed by voiding/obstructive symptoms. Decompensation of the detrusor may occur (over-stretching of the bladder), this can result in residual urine, chronic retention, bladder failure and then renal failure (obstructive nephropathy)

Question 40

How do we manage an over-active bladder?

Answer 40

Overactive bladder (may include detrusor overactivity incontinence) * Lifestyle (cutting back on diuretics such as caffeine and alcohol) * Anti-muscarinics and selective Beta-3 adrenoreceptor agonist * Those medication don't work - we can use intra-detrusor botox therapy into the bladder – calms down the overactive bladder

Question 41

How do we manage stress incontinence?

Answer 41

Stress incontinence * Pelvic floor exercises reduces leakage * Weight loss to reduce strain on pelvic floor * Surgery, autologous rectus abdominis sling or artificial sphincter

Question 42

How do we manage an bladder outlet obstruction?

Answer 42

BOO medical therapies * alpha blockers - relax protstate * 5ARI (5 alpha reductase inhibitors) - reduce prostate hyperplasia * Surgery (stuff to do with the prostate)

Question 43

What do we call and upper and a lower urinary tract infection?

Answer 43

Upper urinary tract – pyelonephritis – upper urinary tract infection Lower urinary tract infection– cystitis

Question 44

What are the risk factors for an uncomplicated UTI?

Answer 44

Normal urinary tract with no immunocompromise - uncomplicated

Question 45

Who gets complicated UTIs? What are the risk factors?

Answer 45

Complicated - Compromised Urinary tract or host defenses Flow of urine outwards is important for preventing UTI – prevents stagnant urine Risk factor for the development of sepsis

Question 46

What organisms are most commonly responsible for UTIs?

Answer 46

Gram positive – thick cell wall – live on dry places of the body – Staph and strep Gram negative – thin cell wall – live in more wet environments – E. Coli (UPEC) and pneuonmiae – main cause of UTIs

Question 47

Where do the bacteria for UTIs commonly come from?

Answer 47

Periurethral contamination from gut/anus to the urethral opening – distance from anus and urethra is predictive for UTIs Illustration - shows how infections can move up the bladder into the kidney and potentially into the blood stream

Question 48

Can constipation increase the risk of a UTI?

Answer 48

Constipation can place pressure urethra – resulting in stagnant urine flow - increased risk of infection

Question 49

Can catheter's increase risk of UTIs?

Answer 49

Catheter increases risk – source of contamination and provides a structure for biofilm formation

Question 50

How can bacteria infect the bladder wall?

Answer 50

Infection of epithelial membrane using type 1 pili – grow and multiply and burst out – infecting more cells Bacteria can go deeper down into deeper layers of the epithelium – lay dormant (immune system can find them and away from antibiotics) – potential theory for recurrent UTIs To cause pyelonephritis bacteria must express pyelonephritis associated (P) pili

Question 51

What are some virulence factors that bacteria have to help them with infection?

Answer 51

Question 52

What host factors do we have to help prevent infection?

Answer 52

Host defenses * Urine has a low pH and high urea – should be protective against infection * Urine flow prevents infection * Mucosa – protective layer * Inhibitors against adherence * Normal inflammatory defense

Question 53

What are some other sites of infection that are possible in male?

Answer 53

Urethritis - urethra Prostatits - prostate - difficult to treat Epididymo-orchitis - epidiymis and testicles Cystitis Pyleonephritis

Question 54

What are the sources of UTI?

Answer 54

Source * Uropathogen from gut * Intracellular bacterial communities/quiescent intracellular reservoirs * Haematogenous – rare

Question 55

Can UTI's seed around the body?

Answer 55

Yes. Bacteraemia common in pyelonephritis - blood Perinephric abscesses - in the kidney's Can rarely lead to remote deep seated infection

Question 56

What is the clinical presentation/symptoms for pyelonephritis?

Answer 56

Pyelonephritis - flank tenderness, loin pain, fever/rigor, sepsis

Question 57

What is the clinical presentation for cystitis?

Answer 57

Cystitis – rarely needs hospitalization – results in dysuria (pain, burning, stinging), frequency, urgency, suprapubic tenderness

Question 58

What extra clinical signs can we see in infants and the elderly with UTIs?

Answer 58

Infants – less than 2 – vomiting and fever Elderly – less localized symptoms - confusion/falls

Question 59

What should you be asking about when taking the clinical history?

Answer 59

Clinical history * Where is dysuria? * Menstrual history * Sexual history Long list of things that cause dysuria – make sure you exclude these other factors – especially for recurrent cystitis

Question 60

When should a dipstick be used for the diagnosis of a UTI?

Answer 60

Useful ONLY in presence of clinical UTI symptoms – presence of nitrites indicate a UTI is a possible diagnosis. As low as 75% sensitivity So.... Only used in confirmation of diagnosis therefore should not be used as a sole investigation Urinary dipstick – only used in patients less than 65 Why? Presence of bacteria in the urine in older people does not necessarily mean there is an infection that requires antibiotics – asymptomatic UTI

Question 61

Are urine cultures used for UTIs? What type of samples are used for a culture?

Answer 61

Urine cultures are used but quite dramatic growth for a positive result is required – low levels could just be periurethral contamination from the gut Culture results **SUPPORT** clinical diagnosis only! Types of sample * Mid stream urine * Clean catch urine * Catheter sample urine CSU – from port not bag * Other – urostomy/cystocopy/pad Generally significant if >10^5 CFU/mL

Question 62

What are the definitions for bacteriuria, significant bacteriuria, asymptomatic bacteriuria and symptomatic bacteriuria?

Answer 62

Bacteriuria - Bacteria in the urine Significant bacteriuria - Indicates that the number of bacteria in the voided urine exceeds the number expected from contamination from the anterior urethra Asymptomatic bacteriuria - Significant bacteriuria in a patient without symptoms - **only ever treated in pregnant women** - risk of pyelonephritis Symptomatic bacteriuria: UTI

Question 63

Is there way we can rapidly detect UTIs?

Answer 63

Flexicult – for primary care – culture at the bedside in 24 h. Rapid test for presence of bacteria, inflammation and antimicrobial resistance genes – still not achieved

Question 64

If someone has significant bacteria in their urine but no symptoms do we treat them?

Answer 64

Only if there are systemic signs or symptoms of a UTI do we prescribe antibiotics

Question 65

What are the main antibiotics used for cystitis in lothian?

Answer 65

Main antibiotics for cystitis * Trimethoprim * Nitrofurantoin * Cefalexin First two toxic to the kidneys (not used for low GFR patients)

Question 66

What role do antibiotics play in treating cystitis? What are the downsides of using antibiotics?

Answer 66

Antibiotics are for amelioration and shortening of symptom duration in cystitis Downfalls * Antimicrobial use increases risk of recurrent UTI * Antimicrobial use increases antimicrobial resistance

Question 67

How do we choose the right antibiotics for treating a UTI?

Answer 67

* Dependent on clinical syndrome (where is the UTI?) - Nitrofurantoin for cystitis ONLY as it won't be active in the blood stream * What is resistance risk? E. Coli – 60-70% is amoxicillin resistant and 30% trim resistance * Oral vs intravenous antibiotics

Question 68

What antibiotics are perscribed for upper UTI/pyelonephritis?

Answer 68

Hospital – UTI – IV gentamicin or amoxicillin Community – co-amoxiclav, ciprofloxacin (side-effects warning) and trimethoprim

Question 69

When should catether associated UTIs only be treated?

Answer 69

Over diagnosed – take a sample from a catheter highly likely to be positive – only treat if there are systemic (fever) symptoms

Question 70

When treating UTIs in the following circumstances, what should we consider? Men - prostate involvement Pregnant women Children

Answer 70

Men – prostate - pain in prostate area – requires longer treatment and require specific antibiotics Pregnant women – avoid contra-indicated and treatment of asymptomatic bacteriuria Children – check whether there is reflux of urine into the bladder – vesico-uteric reflux – common reason for kids requiring dialysis

Question 71

What is some simple advise we can offer in cases where people suffer from recurrent UTIs?

Answer 71

Question 72

What is the definition of recurrent UTIs? What are risk factors for recurrent UTIs?

Answer 72

More than 3 times within a year or more than 2 times in 6 months Risk factor * 1/4 women – common * Increased antimicrobial/biotic exposure Organisms are usually multi-drug resistant Requires MDT to treat