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Flashcards in case 8 Deck (114):
1

bladder

• The urinary bladder is a smooth muscle chamber composed of two main parts:
1. The body – urine collects here.
2. The neck - is a funnel-shaped extension of the body, passing inferiorly and anteriorly into the urogenital triangle and connecting with the urethra. The lower part of the bladder neck is also called the posterior urethra because of its relation to the urethra.

2

detrusor muscle

• The smooth muscle of the bladder is called the detrusor muscle.
 Its muscle fibres extend in all directions.
 When contracted, can the pressure inside the bladder is increased. This allows the emptying of the bladder (normal range = ≤ 15-20 cmH20)
 Smooth muscle cells of the detrusor muscle fuse with one another so that low-resistance electrical pathways exist from one muscle cell to the other.
 Therefore, an action potential can spread throughout the detrusor muscle, from one muscle cell to the next, to cause contraction of the entire bladder at once.

3

trigone of the bladder

• On the posterior wall of the bladder, lying immediately above the bladder neck, is a small triangular area called the trigone.
 The mucosa of trigone is smooth, in contrast to the remaining bladder mucosa, which is folded to form rugae.
 The two ureters enter the bladder at the uppermost angles of the trigone.
 Each ureter, as it enters the bladder, courses obliquely through the detrusor muscle and then passes another 1-2cm beneath the bladder mucosa before emptying into the bladder.

4

posterior urethra

 At the lowermost apex of the trigone, the bladder neck opens into the posterior urethra.
 This is 2-3cm long, and its wall is composed of detrusor muscle interlaced with a large amount of elastic tissue.
 The muscle in this area is called the internal sphincter.
o Its natural tone normally keeps the bladder neck and posterior urethra empty of urine and, therefore, prevents emptying of the bladder until the pressure in the main part of the bladder rises above a critical threshold.

5

external sphincter of the bladder

• Beyond the posterior urethra, the urethra passes through the urogenital diaphragm, which contains a layer of muscle called the external sphincter of the bladder.
 This muscle is a voluntary skeletal muscle, in contrast to the muscle of the bladder body and bladder neck, which is entirely smooth muscle.
 The external sphincter muscle is under voluntary control of the nervous system and can be used to consciously prevent urination even when involuntary controls are attempting to empty the bladder.

6

types of muscle in the bladder

• Internal sphincter = smooth muscle = involuntary control (parasympathetic)
• External sphincter = skeletal muscle = voluntary control (somatic)
• The normal urine flow = 20-50 ml/s

7

parasympathetic innervation of the bladder-autonomic

- the principal nerve supply of the bladder is by way of the PELVIC SPLANCHNIC NERVES, which connect with the spinal cord through the sacral plexus (S2,3,4):
 Sensory nerve fibres(afferent)
 These detect the degree of stretch in the bladder wall.
 Stretch signals from the posterior urethra are especially strong and are mainly responsible for initiating the reflexes that cause bladder emptying.
 Motor nerve fibres (efferent)
 These terminate on ganglion cells located in the wall of the bladder.
 Short postganglionic nerves then innervate the detrusor muscle (M3 receptor).
 This aids micturition.

8

sympathetic innervation of the bladder-autonomic

the bladder receives sympathetic innervation from the sympathetic chain through the HYPOGASTRIC NERVES (L2).
 These cause relaxation of detrusor muscle (B3 receptor) and contraction of urethra (a1 receptor), thus allowing bladder to fill.
 Some sensory nerve fibres also pass by way of the sympathetic nerves and may be important in the sensation of fullness and, in some instances, pain.

9

somatic innervation of the bladder-voluntary

other innervation of the bladder is skeletal motor fibres transmitted through the PUDENDAL NERVE to the external sphincter.
 These innervate and provide voluntary control over the skeletal muscle of the external sphincter (ACh).
 Higher centres can override this contraction and cause the external sphincter to relax.

10

overall innervation to the bladder and its effects

• Parasympathetic nerve fibres (S2,3,4) cause:
 Contraction of detrusor muscle in the body of the bladder (M3 receptor).
 Relaxation of the urethra.
 This aids micturition.

• Sympathetic nerve fibres (T11-L2) cause:
 Relaxation of the detrusor muscle in the body of the bladder (B3 receptor).
 Contraction of the urethra (a1 receptor).
 This aids the filling of the bladder.

• Somatic nerve fibres (S2,3,4) cause:
 Contraction of the external sphincter.
 Higher centres can override this contraction and cause the external sphincter to relax.

11

clinical differences in male and female urethras

The female urethra is distensible because it contains considerable elastic tissue, as well as smooth muscle. It can be easily dilated without injury; consequently, the passage of catheters or cystoscopes is easier in females than in males. Infections of the urethra, and especially the bladder, are more common in women because the female urethra is short, more distensible, and is open to the exterior through the vestibule of the vagina.

12

female urethra

The female urethra (approximately 4 cm long and 6 mm in diameter) passes anteroinferiorly from the internal urethral orifice of the urinary bladder, posterior and then inferior to the pubic symphysis, to the external urethral orifice. The musculature surrounding the internal urethral orifice of the female bladder is not organized into an internal sphincter. In females, the external urethral orifice is located in the vestibule, the cleft between the labia minora of the external genitalia, directly anterior to the vaginal orifice. The urethra lies anterior to the vagina (forming an elevation in the anterior vaginal wall). The urethra passes with the vagina through the pelvic diaphragm, external urethral sphincter, and perineal membrane. Urethral glands are present, particularly in the superior part of the urethra. One group of glands on each side, the paraurethral glands, are homologs to the prostate. These glands have a common paraurethral duct, which opens (one on each side) near the external urethral orifice.

13

male urethra

The male urethra originates at the bladder neck and terminates at the urethral meatus on the glans penis. It is roughly 15-25 cm long in the adult and forms an "S" curve when viewed from a median sagittal plane in an upright, flaccid position.
The male urethra is often divided into 4 segments on the basis of its investing structures:
• Preprostatic urethra (the bladder neck).
• Prostatic urethra.
• Membranous (or intermediate) urethra.
• Spongy (or penile) urethra.

14

prostatic urethra

It originates in the region of the bladder neck, courses roughly 2.5 cm inferiorly, and terminates at the membranous urethra. It lies in a retropubic location and is bordered superiorly by the bladder and supported inferiorly by the external urethral sphincter muscle and the urogenital diaphragm. It is invested in the prostate

15

membranous urethra

The shortest and least distensible portion of the urethra. This region spans from the apex of the prostate to the bulb of the penis. It is invested in the external urethral sphincter muscle and the perineal membrane. The external sphincter is related anteriorly to the dorsal venous complex and is connected to the puboprostatic ligaments and the suspensory ligament of the penis. The external urethral sphincter muscle and the perineal membrane fix the urethra firmly to the ischial rami and inferior pubic rami, rendering this portion of the urethra susceptible to disruption with pelvic fracture.

16

spongey urethra

The spongy urethra is the region that spans the corpus spongiosum of the penis. It is divided into the pendulous urethra and the bulbous (or bulbar) urethra. The pendulous urethra is invested in the corpus spongiosum of the penis in the pendulous portion of the penis. The urethra is located concentrically within the corpus spongiosum. The bulbous urethra is invested in the bulb of the penis, the portion of corpus spongiosum that lies between the split corpora cavernosa in the superficial perineal space.

17

female urethra blood supply and innervation

Blood Supply – Urethral artery (branch of internal pudendal) and vaginal artery. The veins follow the arteries and have similar names.
Innervation – Nerves to the urethra: Vesical plexus & pudendal nerve. Nerves from the urethra: Mostly pelvic splanchnic nerves, but the termination of the urethra has signals transmitted via the pudendal nerve. All afferent nerves = S2-S4

18

male proximal (pre prostatic and prostatic) urethra blood supply and innervation

Blood Supply – Prostatic branches of the inferior vesical & middle rectal arteries. The veins from the proximal 2 parts of the urethra drain into the prostatic venous plexus.
Innervation – Sympathetic, parasympathetic, and visceral afferent nerve fibres run together in nerves of the prostatic plexus (arising from the inferior hypogastric plexus).

19

male distal (membranous and spongey) urethra blood supply and innervation

Blood Supply – Arterial branches arise from the dorsal artery of the penis. Veins accompany the arteries and have similar names.
Innervation - Membranous urethra has the same innervation as the proximal urethra. The spongy urethra has sympathetic innervation from lumbar splanchnic nerves and parasympathetic innervation from pelvic splanchnic nerves (sacral spinal cord level). It transmits visceral afferent fibres alongside the parasympathetic fibres to sacral spinal sensory ganglia. Somatic innervation is provided via the dorsal nerve of the penis (branch of pudendal nerve).

20

lymphatic drainage of the urethra

The lymphatic vessels of the membranous and prostatic urethrae in males and the whole of the urethra in the female, pass to the internal iliac nodes, although a few may enter the external nodes. Vessels coming from the spongy urethra drain with the glans penis into the deep inguinal nodes. Some of the vessels may enter the superficial inguinal nodes and may pass through the inguinal canal to reach the external iliac nodes.
From these nodes they drain into the lateral aortic nodes. From the nodes, efferents issue to the lumbar lymph trunk. The lumbar lymph trunks help to form the abdominal confluence of lymph ducts or the cisterna chyli. Cisterna chyli drains into thoracic duct.

21

micturition

• Micturition is the process by which the urinary bladder empties when it becomes filled.
• This involves two main steps:
1. The bladder fills until the tension in its walls rises above a threshold level.
2. This elicits a nervous reflex called the micturition reflex that empties the bladder or, if this fails, at least causes a conscious desire to urinate.
• Although the micturition reflex is an autonomic spinal cord reflex, it can also be inhibited or facilitated by centres in the cerebral cortex or brain stem.

22

transport of urine from the kidneys to ureters to bladder

• Urine that is expelled from the bladder has the same composition as fluid flowing out of the collecting ducts of the kidneys.
• Urine flows from the collecting ducts into the renal calyces, thus stretching them.
• This increases their pacemaker activity, which in turn initiates peristaltic contractions that spread to the renal pelvis and then downward along the length of the ureter, thereby forcing urine from the renal pelvis to the bladder.

• The walls of the ureters contain smooth muscle.
 These are innervated by both sympathetic and parasympathetic nerves and by an intramural plexus (nerve plexus within the wall) that extends along the entire length of the ureters.
 Peristaltic contractions in the ureter are enhanced by parasympathetic stimulation and inhibited by sympathetic stimulation.

• The ureters enter the bladder through the detrusor muscle in the trigone region.
 The normal tone of the detrusor muscle in the bladder wall tends to compress the ureter, thereby preventing back flow of urine from the bladder when pressure builds up in the bladder during micturition or bladder compression

23

problems of backflow of urine

• Sometimes, the contraction of the bladder during micturition does not always lead to complete occlusion of the ureter (valve).
• As a result, some of the urine in the bladder is propelled backward into the ureter - vesicoureteral reflux.
• Such reflux can lead to enlargement (dilatation) of the ureters.
• If severe it increases the pressure in the renal calyces and the renal medulla, causing renal dysfunction.

24

pain sensation in the ureters - uterorenal reflex

• The ureters are well supplied with pain nerve fibres.
• When a ureter becomes blocked (e.g. by a ureteral stone), intense reflex constriction occurs, associated with severe pain.
• Also, the pain impulses cause a sympathetic reflex back to the kidney to constrict the renal arterioles, thereby decreasing urine output from the kidney.
• This effect is called the ureterorenal reflex and is important for preventing excessive flow of fluid into the pelvis of a kidney with a blocked ureter.

25

micturition reflex

• The micturition contractions are as a result of the micturition reflex.
• Micturition reflex:
 As the bladder is filling, sensory stretch receptors in the bladder wall, especially by the receptors in the posterior urethra, initiate a stretch reflex.
 Sensory signals from these stretch receptors are conducted to the sacral plexus through the ‘sensory’ afferents of the pelvic splanchnic nerves and then reflexively back to the bladder through the ‘motor’ efferent fibres of the same pelvic splanchnic nerves.
 When the bladder is only partially filled, these micturition contractions usually relax and the detrusor muscles stop contracting, and pressure falls back to the baseline.
 As the bladder continues to fill, the micturition reflexes become more frequent and cause greater contractions (more powerful) of the detrusor muscle.

 Once a micturition reflex begins, it is “self-regenerative”.
 That is, initial contraction of the bladder activates the stretch receptors to cause a greater increase in sensory impulses to the bladder and posterior urethra, which causes a further increase in reflex contraction of the bladder; thus, the cycle is repeated again and again until the bladder has reached a strong degree of contraction.
 After a little while, the self-regenerative reflex begins to fatigue and the regenerative cycle of the micturition reflex ceases, permitting the bladder to relax.

26

full bladder and micturation

• As the bladder becomes more and more filled, micturition reflexes occur more frequently and more powerfully.
• Once the micturition reflex becomes powerful enough, it causes another reflex, which passes through the pudendal nerves to the external sphincter to inhibit it.
• If this inhibition is more potent in the brain than the voluntary constrictor signals to the external sphincter, urination will occur.
• If not, urination will not occur until the bladder fills still further and the micturition reflex becomes more powerful.

27

facilitation or inhibition of micturition by the brain

• The micturition reflex is a completely autonomic spinal cord reflex, but it can be inhibited or facilitated by centres in the brain.
• These centres are located in the:
1. Brainstem (pons) – these are strong facilitative and inhibitory centres.
2. Cerebral cortex – these are mainly inhibitory but can become excitatory.
1. The higher centres keep the micturition reflex partially inhibited, except when micturition is desired.
2. The higher centres can prevent micturition, even if the micturition reflex occurs, by continual tonic contraction of the external sphincter until a convenient time presents itself.
3. When it is time to urinate, the cortical centres can facilitate the sacral micturition centres to help initiate a micturition reflex and at the same time inhibit the external urinary sphincter so that urination can occur

28

voluntary urination

is usually initiated in the following way:
1. Voluntary contraction of abdominal muscles.
2. This increases the pressure in the bladder and allows extra urine to enter the bladder neck and posterior urethra under pressure, thus stretching their walls.
3. This stimulates the stretch receptors, which excites the micturition reflex and simultaneously inhibits the external urethral sphincter.
• Ordinarily, all the urine will be emptied, with rarely more than 5-10 ml left in the bladder

29

BPH terminology

Benign Prostatic Enlargement
• BPE
• Clinical Dx
• Benign Prostatic Hyperplasia
• BPH
• Pathological Dx
• Bladder Outflow Obstruction
• BOO
• Urodynamic Dx

30

phytotherapy

Phytotherapy is the study of the use of extracts of natural origin as medicines or health-promoting agents. Phytotherapy medicines differ from plant-derived medicines in standard pharmacology.

31

culture

Definition: Symbolic and learned aspects of society, including
language, custom and convention
(Abercrombie et al, 1994)
 Symbolic aspects of the body influence how people experience and
respond to disease and illness
 Culture influences what is perceived
to be ‘normal’ / the norms of a given society/ group

32

folk models and diet

People draw on popular cultural beliefs about
illness and causation, e.g.
 Hypertension as folk illness: ‘high blood’
 Belief that amount of blood in the body
increases or falls in volume due to diet
 Low blood associated with too much salt, so
salt increased for high blood

33

definition of sex and gender

Sex: The biological and physical
characteristics defining males and females
 Gender: a social construct defined by the
roles, behaviours, responsibilities, activities
and attributes considered appropriate within
a particular society or culture for a man or
woman

34

gender culture and inequalities

A woman cannot receive needed health care because norms in her community
prevent her from travelling alone to a clinic.
◦ A teenage boy dies in an accident because of trying to live up to his peers’
expectations that young men should be "bold" risk-takers.
◦ A married woman contracts HIV because societal standards encourage her husband’s
promiscuity while simultaneously preventing her from insisting on condom use.
◦ A country's lung cancer mortality rate for men far outstrips the corresponding rate
for women because smoking is considered an attractive marker of masculinity, while
it is frowned upon in women.

35

gender differences in access and use of health services

Women have more routine contact
with health services
 Cultural expectations of masculine/
feminine behaviour
 Social relationships
 Wider cultural context
 Preferences for consulting male/
female doctor

36

stigma

branding or marking. enacted is societal reaction with a discriminatory experience. felt is expected societal reactions change their self identity.
worsened health outcomes
cortesy: spread to his connections

37

stigma and urinary symptoms

People with urinary symptoms perceive
themselves to be stigmatised for
behaviours associated with urinary
symptoms
 The stigma of frequency/ urgency is
rooted in social interruption, loss of
control of the body, speculation about
the ‘problem’ & visibility of symptoms
 Men and women experience stigma
related to urinary symptoms differently,
and Hispanic people in particular had a
tendency to keep urinary symptoms a
secret from others

38

what can healthcare providers do about stigma

Need to deliver culturally sensitive healthcare
 Avoid discrimination based on assumptions
about gender and sexuality
 Increase awareness about cultural
sensitivities to promote disclosure of
symptoms and other health information
 Assess for stigma consequences (e.g.
depression and anxiety) and discuss
management options

39

negative emotions and pain

Anxiety and depression predict
postoperative pain (Arpino et al 2004;
Munafó et al 2001)
• Negative emotions can increase
perception of pain
–Experimental study: group in which
negative emotion induced reported
higher levels of pain (immersion of
hand in hot water) (Rainville et al 2005)

40

influence on wound healing

Stress: associated with impaired healing
(see Walburn et al 2009 for review).
• E.g. Marucha et al 1998
–Dental students, punch biopsy to
mouth roof 1) end of vacation, 2) exam
time
–On average, 3 days slower to heal
during exams.

41

stress influence on behaviour

People high in anxiety may find it more
difficult to understand information and
follow instructions
→ could e.g. prolong procedure

42

information provision

Procedural information
–What, when, how?
– Reduce anxiety by eliminating unexpected
anxiety-provoking events (Ridgeway &
Matthews 1982)
• Sensory information
–What will it feel like, look like, sound like, taste like?
–Goal: reduce discrepancy between expected
and actual sensation (Johnson, 1973)
important how word things and when say it - not when on drugs,

43

behavioural instructions

Telling people what they should do – e.g.
–After joint replacement surgery – how
soon should start walking
–Techniques for effective pain control
with analgesia
–How to move after surgery without
damaging wound site.

44

communication behaviours

Difficult to determine anxiety/pain e.g.
Johnston 1982, Marquié et al. 2003
• May be unwilling to bother staff
• Pre-procedure training can facilitate
patients’ communication to staff
• E.g. reassure appropriate to tell staff about
anxiety/pain
• Teach how to communicate – e.g. how to
use quick, easy rating scales

45

cognitive interventions

Change how a person thinks – goal:
reduce negative thinking and/or anxiety
– e.g.:
–Reframing cognitions - training to find
positive responses to worrying
situations – e.g. reason for surgeon’s
visit
– Distraction - encourage thinking about
something else

46

relaxation

Various techniques can be taught – e.g.
–Simple relaxation – systematically relax
each muscle group
–Progressive muscle relaxation – slowly
tense, then relax, each muscle group
–Guided imagery
• Can also practice hypnotic techniques

47

emotion focussed/psychotherapeutic discussion

Discuss worries
• Help patients manage emotions – e.g.
–Put in context of prior experience
–Help to understand emotions, give
them meaning.

48

modelling

Observe a person in similar situation 
learn to cope with that event
–‘mastery model’: model calm, relaxed
–‘coping model’: model finds situation
challenging but successfully copes
• Has been used with adults, but more
commonly used with children.

49

coping styles, monitors and blunters

Miller & Mangan (1983): patients undergoing
colposcopy. 2 types:
– Information seekers (‘monitors’)
– Information avoiders (‘blunters’)
• Different information needs?
• Arousal (pulse rate) lower when information
level provided consistent with coping style.
– Blunters with low information and monitors
with high information least aroused.

50

how to select a condition suitable for screening

The condition should be an important health problem.
• The natural history of the condition should be understood.
• Facility for diagnosis and treatment should be available
• There should be a recognisable latent or early symptomatic
stage.
• There should be a test that is easy to perform and interpret,
acceptable, accurate, reliable, sensitive and specific.
• There should be an accepted treatment recognised for the
disease.
• Treatment should be more effective if started early.
• There should be a policy on who should be treated.
• Diagnosis and treatment should be cost-effective.
• Case-finding should be a continuous process-not a once and
for all project.

51

good screening test

Test validity is the ability of a screening test to
accurately identify diseased and non-disease individuals. An ideal screening test is exquisitely sensitive (high probability of detecting disease) and extremely specific (high probability that those without the disease will screen negative).

52

micturition reflex contraction cant occur if sensory nerve fibres from the bladder to the spinal cord are destroyed:

thereby preventing transmission of stretch signals from the bladder.
 When this happens, a person loses bladder control, despite intact efferent fibres from the cord to the bladder and despite intact neurogenic connections within the brain.
 Instead of emptying periodically, the bladder fills to capacity and overflows a few drops at a time through the urethra.
o This is called overflow incontinence.

 A common cause of atonic bladder is crush injury to the sacral region of the spinal cord.

53

the spinal cord damage above the sacral region:

but the sacral cord segments are still intact.
 As a result, typical micturition reflexes can still occur.
 However, they are no longer controlled by the brain.

54

damage to the brain stem on micturition

 This interrupts most of the inhibitory signals.
 The uninhibited neurogenic bladder results in frequent and relatively uncontrolled micturition.
 Facilitative impulses passing continually down the cord keep the sacral centres so excitable that even a small quantity of urine elicits an uncontrollable micturition reflex, thereby promoting frequent urination

55

prostate gland

• The prostate gland is a compound tubuloalveolar exocrine gland of the male reproductive system.

• The function of the prostate is to secrete a slightly alkaline fluid, milky/white in appearance, that in humans constitutes roughly 30% of the volume of the semen along with spermatozoa and seminal vesicle fluid.
• The alkalinity of semen helps neutralise the acidity of the vaginal tract, prolonging the lifespan of sperm.
• Semen is made alkaline overall with the secretions from the other contributing glands - seminal vesicle fluid.
• The spermatozoa expelled together with mainly seminal vesicular fluid, in comparison to those expelled in prostatic fluid have:
 Better motility
 Longer survival
 Better protection of the genetic material
• The prostate also contains some smooth muscles that help expel semen during ejaculation.

56

structure of the prostate gland

• A healthy male prostate is the size of a walnut.
• It surrounds the urethra just below the urinary bladder and can be felt during a rectal exam.

• Within the prostate, the urethra coming from the bladder is called the prostatic urethra and merges with the 2 ejaculatory ducts (from the seminal vesicles – one form each side of the body).
• The prostate can be divided in 2 ways: by ZONE or by LOBE.
• The prostate does not have a capsule; rather an integral fibromuscular band surrounds it.
• It is sheathed in the muscles of the pelvic floor, which contract during the ejaculatory process.

57

when are zones of the prostate used

in pathology of the prostate

58

transition zone of the prostate

up to 5% of gland at puberty
 This zone surrounds the proximal urethra.
 It is the region of the prostate gland that grows throughout life
 Therefore, responsible for the disease of benign prostatic hyperplasia (BPH)

59

peripheral zone of prostate

– up to 70% of gland
 The sub-capsular portion of the posterior aspect of the prostate gland that surrounds the distal urethra.
 This region is the largest and closest to the rectum - can easily be felt during a digital rectal examination (DRE).
 70–80% of prostatic cancers originate here

60

central zone of prostate

up to 25% of gland
 This zone surrounds the ejaculatory ducts

61

fibromuscular zone

up to 5% of gland
 This isn’t actually a zone but rather a sheath on the anterior aspect of the prostate.
 This zone is usually devoid of glandular components, and composed of muscle and fibrous tissue

62

functions of the prostate: male sexual response

 During male ejaculation, sperm is transmitted from the ductus deferens into the male urethra via the ejaculatory ducts, which lie within the prostate gland.
 During orgasm, smooth muscle tissue in the prostate contracts in order to push semen through the urethra.
 It is possible for men to achieve orgasm solely through stimulation of the prostate gland.

63

secretions of the prostate gland

 The prostatic secretions are a milky white mixture of simple sugars (such as fructose and glucose), enzymes, and alkaline chemicals.
 In the secretions, the protein content is less than 1% and includes:
 Proteolytic enzymes – to break down coagulants and other proteins, to make the semen more viscous
 Citric acid
 Prostatic acid phosphatase
 Beta-microseminoprotein
 Prostate-specific antigen (PSA)
 Zinc – antimicrobial
 The sugars secreted by the prostate function as nutrition for sperm as they pass into the female body to fertilize ova.
 Enzymes work to break down proteins (coagulants) in semen after ejaculation to free sperm cells from the viscous semen.
 The alkaline chemicals in prostatic secretions neutralise acidic vaginal secretions to promote the survival of sperm in the female body

64

regulation of growth and division of the prostate

 Testosterone is produced in the testicles.
 It travels to the prostate and is converted to dihydrotestosterone (DHT) in the stromal cells by the action of the enzyme type 2 5α-reductase.
 Dihydrotestosterone (DHT) is the ultimate mediator of prostatic growth as it causes CELL GROWTH and INHIBITS APOPTOSIS.
 DHT binds to nuclear androgen receptors, which regulate the gene expression that support the growth and survival of prostatic epithelium and stromal cells.
 Although testosterone can also bind to androgen receptors and stimulate growth, DHT is 10 times more potent.
 Binding of DHT to androgen receptor (AR) activates the transcription of androgen-dependent genes.
 DHT is not a direct mitogen for prostate cells, instead DHT-mediated transcription of genes results in the increased production of several growth factors and their receptors.
 Most important among these are members of the fibroblast growth factor (FGF) family, and particularly FGF-7 (keratinocyte growth factor).
 Other growth factors produced in BPH are FGF-1 and FGF-2 which promote fibroblast proliferation.

65

BPH possible cause with DHT

 Although the ultimate cause of BPH is unknown, it is believed that DHT-induced growth factors act by increasing the proliferation of stromal cells and decreasing the death of epithelial cells.
 Clinical symptoms of lower urinary tract obstruction caused by prostatic enlargement may also be exacerbated by contraction of prostatic smooth muscle mediated by α1-adrenergic receptors.

66

controlling the flow of urine

 The urethra runs from the bladder, through the prostate, and out through the penis.
 The muscle fibres of the prostate are wrapped around the urethra and are under involuntary nervous system control (SNS – hypogastric nerve (a1)).
 These fibres contract to slow and stop the flow of urine.

67

summary of male urinary system

• The male urinary system is made up of the kidneys which produce urine, the ureters connecting the kidneys to the bladder where urine is stored and the urethra, the exit passage way from the bladder.
• The male genital system begins with the 2 testis where sperm is produced.
• The epididymis is system of convoluted small tubules leading from each testis and emptying into the vas deferens.
• After being joined by the duct of the seminal vesicles, the vas deferens becomes the ejaculatory duct which enters the prostate where it joins with the urethra to convey the sperm contained in semen to the penis.
• The walnut sized prostate gland is situated just beneath the bladder and encircles the upper part of the urethra.
• It secretes alkaline fluids rich in enzymes and prostaglandins.
• This secretion is important to the survival and performance of the sperm.

• The seminal vesicles also play an important role in contributing secretions which enhance the sperms chance of success.
• During ejaculation the connection between the bladder and the urethra is closed while the prostate, seminal vesicles, urethra and the penis all undergo rhythmical contraction moving forward the semen which is composed semen plus secretions from the prostate, seminal vesicles and minor glands.

68

benign prostate hyperplasia

• The aging male is prone to developing enlargement of the prostate known as BPH.
• The prostate contains small glands, muscle fibres and connective tissue.
 In BPH all of these enlarge, resulting in the enlargement of the prostate gland.
• The first changes in BPH involve proliferation of glandular tissue in the transitional zone.
• New cells are constantly being formed by division as a result of the pathogenesis of BPH.
• Room has to be made for these new cells by a special process of apoptosis so that in normal health the number of cells being produced is balanced by the number of cells being removed.
• Impairment of apoptosis is thought to be an important factor in causing BPH.
• As the prostate enlarges, it compresses the prostatic urethra, causing disruption to the normal flow of urine.
• When epithelial cells multiply excessively in either BPH or in prostate cancer, they may release an excessive amount of a glycoprotein called prostate specific antigen (PSA) into the circulation (normal range = 0-4ng/ml):
 Normally, the prostate epithelial cells secrete prostate 'specific' antigen (PSA). This is required to liquefy the semen.
 The level of this will increase if the prostate enlarges because there are more epithelial cells secreting PSA.
 In prostate cancer, there are more cells than in BPH. Therefore, in prostate cancer, the level of PSA in the blood is greater than that in BPH.

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epidemiology

• BPH is an extremely common disorder in men over 50-65.
• Incidence:
 Histologic evidence can be seen in approximately 20% men aged 40.
 Only 50% of those who have microscopic evidence of BPH have clinically detectable enlargement of the prostate, and of these individuals, only 50% develop clinical symptoms.
 30% of white Americans over 50 years having moderate-severe symptoms

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symptoms of BPH

• BPH may cause lower UT symptoms.
• Storage Symptoms:
 Going frequently to pass urine
 A feeling that the bladder is full (urgency)
 Waking up at night to pass urine (nocturia)
 Leakage of urine when one does not get to the toilet in time (urge incontinence)
• Voiding Symptoms:
 Needing to wait for the stream to start (hesitancy)
 Weak stream
 The stream starts and stops intermittently
 Having to push and strain to pass urine
 Dribbling at the end of urination
 Sensation of incomplete bladder emptying
• Sometimes, despite urination, the bladder may not empty completely causing a large post-void residual urinary problem, increasing the risk of infection/ bladder stone formation/ cancer development.

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complications of BPH

• Infection

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investigations

• Abdominal examination – usually palpate to check for a distended bladder.
• Rectal examination – prostate feels enlarged
• but smooth. (nodules would indicate cancer

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drugs anti androgen

Finasteride/dutasteride
Block the enzyme 5α-reductase type 2.
This slows the conversion of testosterone into DHT, thus slowing down the growth of the stromal and epithelial prostate cells.
This also promotes apoptosis. Benifits: Safe
Reduce prostate volume
Reverse pathology
Reduced risk of complications
Reduce risk of surgery
Drawbacks: Slow Acting
Erectile Dysfunction
Gynaecomastia
Reduced Libido
Reduce PSA too much,
reduces PSA due to promotion of apoptosis

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a1 Adrenergic receptor antagonists

Tamsulosin/Alfuzosin/doxazosin
Competitive inhibition for the binding site of the α1-adrenergic receptors.
Causes prostatic smooth muscle relaxation.
This reduces urethral occlusion.
These drugs may also encourage apoptosis.
Quick Acting
Safe
Selective
Long Lasting
Dizziness
Drowsiness
Headaches
Little or no sperm on edjaculation
has no effect on PSA

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drugs for BPH

• Both these drugs are given in combination because the anti-androgen drugs are better, but they are short acting.

• Phytotherapy may also be used – ‘saw palmetto’ extracts.

• In acute retention or retention with overflow, the first priorities are to relieve pain and to establish urethral catheter drainage.

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surgery

• Deterioration in renal function or the development of upper tract dilatation requires surgery.
• There are a few procedures that can be carried out:
 Bladder neck incision
 Trans-urethral resection of prostate (TURP)
 Holium laser enucleation of prostate (HOLEP)
 Open prostectomy Prostatic stent

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Transurethral resection of the prostate (TURP)/Transurethral Prostatectomy

• This has been the gold standard in terms of reducing symptoms, improving flow rates, and decreasing post-voiding residual urine.
• It is indicated as a first line of therapy in recurrent urinary retention.
• If urethral catheterisation is impossible, suprapubic catheter drainage should be done

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procedure for Transurethral resection of the prostate (TURP)/Transurethral Prostatectomy

• A surgical procedure that removes part/all of the prostate.
• This would be necessary if:
 The first treatments for prostate enlargement, such as medication, fail to control symptoms.
 An enlarged prostate leads to complications such as bladder stones, infections or difficulty emptying it.

• This is performed under general/spinal anaesthesia:
 General – unconscious throughout the procedure
 Spinal/epidural – awake throughout but not feel anything

• A device called the resectoscope is used which is a thin metal tube consisting of a light, a camera and a loop wire.
• The resectoscope is inserted into the urethra and guided to the site of the prostate.
• An electric current is used to heat the loop of wire, and the heated wire is used to cut away the section of your prostate that is causing the symptoms.
• After the procedure, a catheter is used to pump saline water into the bladder and flush away pieces of prostate that have been removed.

• The advantages of this technique are:

 No strain to urinate
 More control over holding in urine
 No more nocturia
 Stronger stream of urine
 No more pads

• The disadvantages include:
 Loss of ability to ejaculate (retrograde ejaculation – 70%) and ED
 Stricture (narrowing)
• Before the surgery, NaCl is administered IV.
• This is to make the smooth muscles in the prostate and the bladder more apparent.
• Glycine may also be used for this purpose, but the prostatic venous sinuses absorb this – it is then metabolized in the portal bed and kidneys. Ammonia is a major by-product of glycine metabolism

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Holmium Laser Enucleation of the Prostate (HOLEP)

• An alternative to this method is the Holmium laser enucleation of the prostate (HOLEP):
 In this a laser is used to separate excess tissue from the prostate into the bladder and the tissue is then removed.
 HOLEP causes less blood loss, involves a shorter stay in hospital and is suitable for moderate to large prostates

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pathogenesis of BPH

• Mainly due to impaired cell death – lack of apoptosis.
• This results in the accumulation of senescent cells in the prostate.
• Androgens (mainly DHT), which mediate the development of BPH, can not only increase cellular proliferation, but also inhibit cell death.
• Stromal cells are responsible for androgen-dependent prostatic growth because the type 2 5α-reductase enzyme is only found in the stromal cells.

• As well as the enlargement of the glandular tissue, fibroblasts also proliferate and enlarge.
 This is because of excessive FGF growth factors.
 As a result of this fibrosis, the bladder wall can’t contract properly and so there is residual urine volume left over always, increasing the risk of infections etc

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prostate cancer

• In prostate cancer the growth and multiplication of cells escapes from normal control.
• In addition there is impairment of apoptosis (usually a gene mutation of p53).
• Prostate cancer usually occurs in the peripheral zone of the prostate.
• Unlike the situation in BPH where cell multiplication is much more controlled, in prostate carcinoma the malignant cells multiply out of control, begin to invade the stroma which is the connective tissue of the prostate and extend beyond it to the surrounding structures such as the seminal vesicles.
• Having breached the capsule, the tumour is now able to spread more widely.
• Malignant cells may invade the lymphatic system travelling to regional lymph nodes and then onto the liver and/or lungs.
• If tumour cells enter the blood stream they can metastasise to the bones as well

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epidemiology of prostate cancer

• Prostatic carcinoma accounts for 7% of all cancers in men.
• It is the 6th most common cancer in the world.
• Malignant change within the prostate becomes increasingly common with advancing age.
• By the age of 80 years, 80% of men have malignant foci within the gland, but most of these appear to lie dormant.
• Histologically, the tumour is an adenocarcinoma.
• Hormonal factors (androgens) are thought to play a role in the aetiology.

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screening methods

• Serum prostate-specific antigen (PSA) can be used for the detection of this cancer.
• Many men over 70 have evidence of prostate cancer at post mortem with no symptoms of the disease and it has been suggested that over 75-year-olds should not have screening PSAs.
• The test must be interpreted with caution due to the natural increase in PSA with age, BPH and with prostatitis.
• It may be life saving for the individual diagnosed with a high grade tumour that is still amenable to curative treatment.

• There is a dilemma with the screening of prostate cancer.
• This is because such screening methods can lead to over-diagnosing of patients who don’t require treatment.
• As a result, a lot of the healthcare money is wasted on such treatment.

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urinary tract obstruction

• Obstruction increases susceptibility to infection and to stone formation, and unrelieved obstruction almost always leads to permanent renal atrophy (hydronephrosis).
• Obstruction may be sudden or insidious, partial or complete, unilateral or bilateral; it may occur at any level of the urinary tract from the urethra to the renal pelvis.
• The most common sites of UT obstruction causes by a kidney stone are: (1) uretropelvic junction (between ureter and renal pelvis), (2) pelvic brim (where ureters cross the bifurcation of common iliac artery), (3) uretrovesicular junction (where the ureters enter the bladder).
• Hydronephrosis is dilation of the renal pelvis and calyces associated with progressive atrophy of the kidney due to obstruction to the outflow of urine.
• Even with complete obstruction, glomerular filtration persists.
• Because of this continued filtration, the affected calyces and pelvis become dilated.
• The high pressure in the pelvis is transmitted back through the collecting ducts into the renal cortex, causing renal atrophy, but it also compresses the renal vasculature of the medulla, causing a diminution in inner medullary blood flow, both the perfusion and clearance are deficient (this can be picked up on a dynamic isotope renogram)
• The medullary vascular defects are initially reversible, but lead to medullary functional disturbances.
• Accordingly, the initial functional alterations caused by obstruction are largely tubular, manifested primarily by impaired concentrating ability (can lead to metabolic acidosis).
• Only later does the GFR begin to fall.
• Obstruction also triggers an interstitial inflammatory reaction, leading eventually to interstitial fibrosis.

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hydronephrosis

dilation of the renal pelvis and calyces associated with progressive atrophy of the kidney due to obstruction to the outflow of urine.

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clinical features of UTI

 Acute obstruction may provoke pain attributed to distention of the collecting system or renal capsule.
 Most of the early symptoms are produced by the underlying cause of the hydronephrosis.
 Unilateral complete or partial hydronephrosis may remain silent for long periods, since the unaffected kidney can maintain adequate renal function.
 Ultrasonography is a useful non-invasive technique in the diagnosis of obstructive uropathy.
 In bilateral partial obstruction the earliest manifestation is inability to concentrate the urine, reflected by polyuria and nocturia.
 Complete bilateral obstruction results in oliguria (small amounts of urine production) or anuria and is incompatible with survival unless the obstruction is relieved.
 Curiously, after relief of complete urinary tract obstruction, postobstructive diuresis occurs.
 This can often be massive, with the kidney excreting large amounts of urine that is rich in sodium chloride.

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epidemiology of age associated diseases including urinary incontinence

• Progressive sclerosis of glomeruli occurs with ageing and this, together with the development of atheromatous renal vascular disease, accounts for the progressive reduction in GFR seen with advancing years.
• A GFR of 50–60 mL/min (about half the normal value for a young adult) may be regarded as ‘normal’ in patients in their 80’s.
• The reduction in muscle mass often seen with ageing may mask this deterioration in renal function in that the serum creatinine concentration may be less than 120mmol/L in an elderly patient whose GFR is 50 mL/min or lower.
• The serum creatinine as a measure of renal function in elderly must take this into account.

• Urinary incontinence is common in the elderly with 25% of women and 15% of men over 65 having a problem.

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acute renal failure

• Acute renal failure is defined as an abrupt decline in the renal function with increased creatinine and increased blood urea nitrogen levels (uraemia).

• This is failure of renal excretory function due to depression of the GFR.
• This is accompanied to a variable extent by:
 Failure of erythropoietin production (this can lead to a low Hb count and cause anaemia)
 Failure of vitamin D hydroxylation
 Failure of regulation of acid–base balance (this can lead to metabolic acidosis)
 Failure of regulation of salt and water balance and blood pressure.

• Classification
 Renal failure results in reduced excretion of nitrogenous waste products (e.g. urea).
 A raised serum urea concentration (uraemia) is classified as:
 Prerenal – caused by impaired perfusion to the kidneys.
 Renal – caused by acute tubular necrosis/ iscahemia/ toxins.
 Postrenal – caused by obstruction in the urinary tract.

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classification of renal failure

 Renal failure results in reduced excretion of nitrogenous waste products (e.g. urea).
 A raised serum urea concentration (uraemia) is classified as:
 Prerenal – caused by impaired perfusion to the kidneys.
 Renal – caused by acute tubular necrosis/ iscahemia/ toxins.
 Postrenal – caused by obstruction in the urinary tract

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lab tests-cloudy urine

• Due to mild presence of semen in the urine (after retro-ejaculation)/ UTI/ presence of proteins in the urine/ dehydration.

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urine sample tests

• This tests for sugar, protein, or blood in the urine.
• Can be carried out quickly as a urine dipstick test.
• Blood can signify diseases in the kidney, urinary system or bladder.
• Sugar is a sign of diabetes.
• Protein would indicate kidney disease.
• PSA can indicate cancer

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filled and distended bladder

• A cause of this is an enlarged prostate.
• The prostate can block off the urethra, which makes urinating difficult, if not impossible.
• A person with a distended bladder will not be able to urinate, even if they feel the urge to do so.
• They may also feel some pain in the lower abdomen as a result of the condition

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decreased urine Na+ and dec osmolarity

• Sodium test is used to see whether a patient is properly hydrated.
• It also evaluates kidney function.

• Due to atrophy of the kidney parenc hyma, perfusion and clearance in the kidney is highly affected:
 This means that the kidney is not able to filter the blood well or clear it so all the sodium filtered is not reabsorbed back into the blood so there is a decrease.
 Also, the backflow of urine increases the tubular fluid in the kidneys. This dilutes the Na+ ions present in the tubular fluid in the kidneys, thus decreasing the osmolarity of the urine.

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serum electrolytes: hyperkalaemia

• This is due to the fact that there is renal dysfunction and so the person cannot secrete K+ into the tubular fluid (urine).
• Therefore, K+ ions build up in the cells.

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decreased blood PH

• This is due to renal dysfunction.
• The kidney is unable to secrete H+ ions into the urine.
• The kidney is unable to reabsorb HCO3- ions from urine.
• This causes metabolic acidosis, and a subsequent decrease in the pH

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dec pCO2

• Due to the metabolic acidosis, the patient hyperventilates as respiratory compensation.
• This means the person hyperventilates and so the pCO2 decreases

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serum urea and creatinine elevated

• Due to renal dysfunction, urea isn’t secreted into urine, and so it build up in the blood.
• Also, there is less perfusion to the kidneys and so urea and creatinine cannot be filtered into the nephron through the glomerulus, and so builds up in the blood.

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haemoglobin conc. 9.4g/dl

• Due to renal dysfunction, the kidneys secrete less erythropoietin into the blood.
• This means that there is reduced maturation of the RBCs, and a subsequent drop in the level of serum haemoglobin.
• Normal haemoglobin range = 13-18 g/dl

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imaging the kidney

• There are many ways to image the kidney:

 Abdominal radiographs
 Ultrasound
 Fluoroscopy
 Nuclear medicine
 CT
 MRI

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abdominal radiograph

• This involves imagining of the kidney, ureter and bladder (KUB)
• Radiation is used
• Primary indication is urinary tract calculus
• Intravenous urography (IVU)
 This is an x-ray procedure used to assess problems in the KUB.
 A contrast dye is injected intravenously.

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ultrasounds

• Involves imaging of the kidneys and the urinary bladder only.
• The testes can also be imaged using ultrasound.
• There is no radiation involved. Only the use of sound waves.
• This is used commonly in paediatric radiology.

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fluroscopy

• Involved imaging of kidneys, ureters and bladder (KUB).
• This is used as part of a screening regime.
• There is continual use of x-rays (radiation).
• Cystograms are used in paediatric radiology. A cystogram is an examination that takes pictures of the bladder and urethra.
 Contrast material is introduced into your bladder through the catheter, then x-rays are taken.
• It can be used for urethrograms too.

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computed tomography CT

• Rotating x-ray tube and detector
• IV contrast – renal function
• Urinary tract calculi
• Renal tumours
• Urinary tract tumours
• Cancer staging
• Renal cyst characterisation

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magnetic resonance imaging MRI

• Magnet and coils : radiowaves and magnetic fields
• No radiation
• Soft tissue
• IV contrast
• Time
• Diffusion weighted imaging – multi-parametric imaging for prostate cancer
• Renal lesion characterisation
• Renal and urinary tract tumours
• Prostate cancer

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nuclear medicine

• Radioactive tracer and Gamma camera
• Radiation
• Assessment of function
• Technetium-99m
• DMSA : dimercaptosuccinic acid
• MAG 3 : mercaptoacetyltriglycine

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hyperkalemia

Hyperkalemia is a serious medical condition that can cause severe cardiac electrophysiology alterations, such as cardiac arrhythmias, and sudden death. Hyperkalemia is defined as a serum potassium level above the reference range and arbitrary thresholds are used to indicate degree of severity, such as >5.0, >5.5 or >6.0 mmol/L. Patients with chronic kidney disease (CKD) (especially advanced CKD) are at high risk for hyperkalemia, especially when other factors and comorbidities that interfere with renal potassium excretion are present. The prevalence of hyperkalemia in CKD patients is considerably higher than in the general population. A recent review reports hyperkalemia frequency as high as 40-50% in the CKD population compared to 2-3% in the general population. Those at highest risk are patients with diabetes and advanced CKD, kidney transplant recipients, and patients treated with renin-angiotensin aldosterone system (RAAS) inhibitors. Moreover, an episode of hyperkalemia in patients with CKD increases the odds of mortality within one day of the event. There may also be racial differences for hyperkalemia outcomes. According to a retrospective observational study of 1227 patients, white patients with CKD have a consistent association between hyperkalemia and increased mortality, while African American/black patients with CKD appear to have a better tolerance of high potassium levels; but these results need to be confirmed by prospective studies

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potassium homeostasis

The kidneys play a major role in maintaining potassium homeostasis by matching potassium intake with potassium excretion. Potassium is freely filtered by the glomerulus and 90-95% is reabsorbed in the proximal tubule and loop of Henle. Urinary excretion of potassium begins in the distal convoluted tubule and is further regulated by the distal nephron and collecting duct.Therefore, loss of nephron function due to kidney disease results in renal retention of potassium. The main regulators of this process are aldosterone and serum potassium level. Increases in serum potassium level correlate with worsening kidney function. As glomerular filtration rate (GFR) declines, potassium excretion is maintained by changes in the remaining nephrons that increase efficacy of potassium excretion. Due to this adaptive response, under normal conditions hyperkalemia rarely occurs at GFR >15 mL/min, unless aldosterone secretion or function is impaired. But there is a limit to renal compensation and as the GFR falls below 15 mL/min, extrarenal handling of potassium, especially gastrointestinal excretion, becomes critical in dissipating an acute potassium load. Importantly, the capacity of the colon to secrete potassium increases as kidney function declines and makes a substantial contribution to potassium homeostasis in patients with CKD. Research shows that under basal conditions, fecal potassium excretion was almost three-fold greater in kidney failure patients, compared to patients with normal kidney function.In a case report of a hemodialysis patient, severe hyperkalemia was seen due to reduced colonic potassium secretion following colon diversion surgery. This was evidenced by changes in fecal potassium before and after restored bowel continuity, without dietary modification.

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hyperkalemia in CKD

In addition to a decrease in GFR and disturbances in renal handling of potassium, CKD patients often have other factors and comorbidities that worsen hyperkalemia. These factors described below explain why hyperkalemia is commonly seen in the CKD population:
•Dietary modifications for CKD– Increased dietary potassium intake from salt substitute (potassium chloride), potassium-rich heart-healthy diets, and herbal supplements (noni, alfalfa, dandelion, etc.)
•Metabolic acidosis– Potassium shift from the intracellular to the extracellular space
•Anemia requiring blood transfusion– High acute potassium load (large transfusions, outdated blood)
•Kidney transplant– Effects of calcineurin inhibitors are the prime offenders in this category. Renal tubular acidosis contributes to a lesser extent.
•Acute kidney injury– Rapid decrease in GFR and tubular flow; often accompanied by a hypercatabolic state, tissue injury, and high acute potassium loads
•Diabetes– Insulin deficiency and hypertonicity caused by hyperglycemia contribute to an inability to disperse high acute potassium load into the intracellular space. Hyporeninemic hypoaldosteronism results in the inability to upregulate tubular potassium secretion.
•Cardiovascular disease (CVD) and associated conditions– Require medical treatments that have been linked to hyperkalemia (eg mineralocorticoid-receptor blockers, cardiac glycosides)
•Advanced stages of heart failure– Reductions in renal perfusion

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other risk facters of hyperkalemia

Other reported independent risk factors for hyperkalemia in patients with CVD and CKD include coronary artery disease and peripheral vascular disease. This association could be due to the role of aldosterone in regulating potassium homeostasis, oxidative stress, and atherosclerosis.The most common cause of increased potassium levels as related to morbidity and mortality is drug-induced hyperkalemia, triggered either by inhibiting renal potassium excretion or by blocking extrarenal removal. In an observational retrospective study of nondialyzed patients with serum potassium of 6.5 mmol/L or greater on admission or during hospital stay, more than 60% were taking at least one drug known to cause or worsen hyperkalemia. Treatment with RAAS inhibitors, such as angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blockers (ARB), is widely used for managing CKD progression, but linked with an increased risk of hyperkalemia, especially when administered in combination. In a study of veterans with proteinuric diabetic kidney disease, the risk of hyperkalemia was more than double in the combination-therapy group (ACE inhibitor and ARB) compared to the monotherapy group, and the study was stopped early due to safety concerns. In a cohort study of patients with possible CKD who started an ACE inhibitor, investigators identified seven patient characteristics that predicted 90-day risk of hyperkalemia: advanced age (80-89 years), declining kidney function, diabetes, heart failure, high starting dose of ACE inhibitor (>10 mg/day), current use of potassium supplements, and current use of ARB or potassium-sparing diuretics. Of course, for RAAS blockade therapy, the higher the baseline serum potassium the higher the risk of hyperkalemia. Risk predictors may be useful for more intensive potassium monitoring and subsequent intervention in CKD patients on RAAS inhibitors. There is a high prevalence of nonsteroidal anti-inflammatory drug (NSAID) use, especially by the elderly, and approximately 14 million people in the U.S. are treated with both antihypertensive drugs and NSAIDs. The strongest risk factors for NSAID-induced hyperkalemia include prior episode of hyperkalemia, CKD, diabetes, acute kidney injury, and use of potassium-sparing diuretics. Risk of hyperkalemia with use of selective cyclo-oxygenase (COX)-2 inhibitors versus nonselective NSAIDS is not clear. Aljadhey et al report clinically important increases in serum potassium in patients prescribed selective COX-2 inhibitors, putting them at risk for hyperkalemia or cardiovascular events. Whereas Lafrance et al suggest that certain NSAIDs may increase the risk of hyperkalemia, not in relation to COX-2 selectivity of the NSAID, but may depend on concurrent use of other agents.Larger studies are needed to confirm these results.

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hypoplasia

too few nephrons

111

dysplasia

undifferentiated kidney sometimes with cysts

112

agenesis

absent kidney

113

PAX2

PAX2 is expressed in the developing eye and renal
tract. It prevents death of undifferentiated cells

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casues of aquired kidney failure

‘Pre-renal’ causes
►Shock (e.g. massive blood loss, septicaemia)
►Cardiac and Liver failure
Intrinsic kidney disease
► Glomerular disease (e.g. Alport syndrome, diabetes
mellitus and immune-mediated glomerulonephritis)
►Tubular disease (e.g. pyelonephritis, autosomal
dominant polycystic disease, nephrotoxins)
‘Post-renal’ causes
►Urinary flow impairment (e.g. stones, tumours and
dysfunctional bladders); need to block both kidneys