CASE 8

Question 1

what categories can tumour markers be divided into?

Answer 1

• monoclonal antibodies against carbohydrate or glycoproteins tumour antigens
• tumour antigens
• enzymes (ALP, neurone specific enolase)
• hormones (eg. calcitonin, ADH)

Question 2

tumour markers usually have a ______

Answer 2

low specificity

Question 3

what monoclonal antibodies can be used to identify ovarian, pancreatic and breast cancers?

Answer 3

ovarian = CA 125
pancreatic = CA 19-9
breast = CA 15-3

Question 4

what tumour antigen is used to identify prostatic carcinoma?

Answer 4

prostate specific antigen (PSA)

Question 5

what tumour antigen can be used to identify hepatocellular carcinoma, teratoma?

Answer 5

alpha-feto protein (AFP)

Question 6

what tumour antigen can be used to identify colorectal cancer?

Answer 6

carcinoembryonic antigen (CEA)

Question 7

what tumour antigen can be used to identify melanoma, schwannomas?

Answer 7

S-100

Question 8

what tumour antigen can be used to identify neuroblastoma?

Answer 8

bombesin

Question 9

what is PSA?

Answer 9

= prostate specific antigen

= a serine protease enzyme produced by normal and malignant prostate epithelial cells

Question 10

what are the age-adjusted upper limits for PSA recommended by the Prostate Cancer Risk Management programme (PCRMP)?

Answer 10

50-59 years = 3.0

60-69 years = 4.0

> 70 years = 5.0

Question 11

what does NICE recommend as the cut off PSA?

Answer 11

men aged 50-69 years should be referred if the PSA is >= 3.0 ng/ml OR there is an abnormal DRE

note this is a lower threshold than the PCRMP 60-69 years limits recommended above

Question 12

what can PSA be raised by?

Answer 12

• benign prostatic hyperplasia (BPH)
• prostatitis and UTI (NICE recommend to postpone the PSA test for at least 1 month after treatment)
• ejaculation (ideally not in the previous 48 hours)
• vigorous exercise (ideally not in the previous 48 hours)
• urinary retention
• instrumentation of the urinary tract

whether DRE actually causes a rise in PSA levels is a matter of debate

Question 13

around ___% of men with a PSA of 4-10 ng/ml will be found to have prostate cancer. with a PSA of 10-20 ng/ml this rises to ___% of men.

around __% with prostate cancer have a normal PSA

various methods are used to try and add greater meaning to a PSA level including age-adjusted upper limits and monitoring change in PSA level with time (PSA velocity or PSA doubling time)

Answer 13

• 33%
• 60%
• 20%

Question 14

what is inclusion health?

Answer 14

a growing discipline that aims to prevent and redress health and social inequities among people in extremes of poor health due to poverty, marginalisation, and multiple morbidity

Question 15

asylum seekers vs refugees

Answer 15

• asylum seekers in process of being assessed to gain legal status
• refugees have ‘status’ or leave to remain— often temporary

Question 16

what is utilitarianism?

Answer 16

Utilitarianism is an ethical theory that determines right from wrong by focusing on outcomes. It is a form of consequentialism. Utilitarianism holds that the most ethical choice is the one that will produce the greatest good for the greatest number.

outcome is more important than action
aim to maximise the ‘good’
utility = human welfare/well-being
utilitarianism aims to maximise human welfare

Question 17

describe Maslow’s hierarchy of needs

Answer 17

Question 18

describe virtue ethics

Answer 18

• collection of normative ethical philosophies that focus on how we ought to act
• being, rather than doing
• morality stems from character of individual

Question 19

what are the 3 approaches to ethics?

Answer 19

1. virtue ethics = an action is only right if it is an action that a virtuous person would carry out in the same circumstances
2. consequentialism = a theory that says whether something is good or bad depends on its outcomes
3. deontology = a theory that says actions are good or bad according to a clear set of rules

Question 20

equality vs equity vs justice

Answer 20

equality = dividing resources equally but does not factor differences in need and ability. Everybody is given the exact same quantity of resources

equity = not only dividing resources fairly and equally, but also factoring in differences amongst people.

justice = long-term equity. It looks to create equity in systems as well as individuals

Question 21

obesity and PSA?

Answer 21

lower

Question 22

low vs high creatinine

Answer 22

high in renal failure

low if low muscle mass

Question 23

what electrolyte problem can you get from a transurethral resection of the prostate (TURP)?

Answer 23

hyponatraemia

Question 24

where do the 2 ureters enter the bladder?

Answer 24

at the uppermost angles of the trigone

Question 25

what does the bladder neck open into at the lowermost apex of the trigone?

Answer 25

posterior urethra

Question 26

internal vs external sphincter muscle and innervation

Answer 26

internal = smooth muscle = involuntary control (PS) external = skeletal muscle = voluntary control (somatic)

Question 27

what is normal urine flow?

Answer 27

20-50 ml/s

Question 28

somatic innervation to the bladder?

Answer 28

pudendal nerve — voluntary contraction of external sphincter

Question 29

parasympathetic vs sympathetic bladder innervation

Answer 29

PS = pelvic splanchnic nerve S = hypogastric nerve

Question 30

what is micturition?

Answer 30

the process by which the urinary bladder empties when it becomes filled

Question 31

micturition involves what 2 main steps?

Answer 31

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

Question 32

what area of the brain is responsible for coordinating the actions of the urinary sphincters and the bladder, and invpv;ed in the storage phase?

Answer 32

To stimulate storage, impulses from the cerebral cortex travel to the pons. The pons is responsible for co-ordinating the actions of the urinary sphincters and the bladder, and the area involved in the storage phase is the pontine continence centre (on the left-hand side of the pons).

Question 33

roots of hypogastric nerve

Answer 33

T10-L2

Question 34

what does the hypogastric nerve stimulate at the bladder?

Answer 34

Relaxation of the detrusor muscle in the bladder wall – via stimulation of β3-adrenoreceptors in the fundus and the body of the bladder. Contraction of the IUS – via stimulation of α1-adrenoreceptors at the neck of the bladder

Question 35

how is somatic innervation involved in the storage phase of micturition?

Answer 35

the EUS is under voluntary somatic control. In the storage phase, impulses travel to the EUS via the pudendal nerve (nerve roots S2-S4) to nicotinic (cholinergic) receptors on the striated muscle, resulting in contraction of the EUS. This prevents any urine from leaking out.

Question 36

stress vs urge vs overflow vs neurological incontinence

Answer 36

Stress incontinence – urine leakage when pressure is exerted on the bladder. This is common in pregnancy and can sometimes happen when laughing or sneezing, due to increased intra-abdominal pressure Urge incontinence – urine leakage as soon as the urge to urinate arise. This is seen in urinary tract infections (UTIs) and can also be caused by medications, alcohol or caffeine. Overflow incontinence – urine leakage due to the bladder being overfilled. Causes of this include bladder stones and chronic urinary retention. Neurological incontinence – urine leakage caused by nerve lesions or neurological conditions, such as multiple sclerosis or spinal cord compression

Question 37

what are the effects of a spinal cord lesion above T12 on the bladder?

Answer 37

In an upper motor neuron lesion, sympathetic input to the bladder is lost, leading to an inability for the detrusor muscle to relax, or the IUS to contract. Afferent signals via the sensory pelvic nerve are also unable to reach the brain, so the EUS remains constantly relaxed. The result is decreased bladder capacity and detrusor overactivity. The parasympathetic system initiates detrusor wall contraction in response to bladder wall stretch, resulting in the bladder automatically emptying as it fills. This is known as a reflex bladder. The causes of such spinal cord injuries include trauma and multiple sclerosis.

Question 38

what can be used to treat incontinence?

Answer 38

Anticholinergics (e.g. Oxybutynin, Tolterodine) – these reduce parasympathetic input to the bladder. However, anticholinergics can cause side effects such as a dry mouth or constipation, therefore are not used frequently. Oxybutynin in particular should be avoided in frail patients, due to an increased risk of falls. β3-adrenoceptor agonists (e.g. Mirabegron) – these drugs bind to β3-receptors on the detrusor muscle to cause relaxation. By doing so, these drugs increase the bladder’s capacity to store urine. β3-receptors are particularly useful for treating urge urinary incontinence. Other possible therapies include the injection of botulinum toxin A, sacral nerve stimulation, and surgical procedures such as Augmentation enterocystoplasty or urinary diversion.

Question 39

passing of urine is under what control?

Answer 39

parasympathetic

Question 40

Upon the voluntary decision to urinate, neurons of the pontine micturition centre fire to excite what?

Answer 40

the sacral preganglionic neurons

Question 41

describe parasympathetic stimulation in the voiding phase of micturition

Answer 41

parasympathetic stimulation to the pelvic nerve (nerve roots S2-4) causes a release of acetylcholine (ACh), which works on muscarinic ACh receptors (M3 receptors) on the detrusor muscle, causing it to contract and increase intra-vesicular pressure. The pontine micturition centre also inhibits Onuf’s nucleus, with a resultant reduction in sympathetic stimulation to the internal urethral sphincter causing relaxation.

Question 42

what is vesical tenesmus?

Answer 42

the feeling of incomplete emptying of the bladder following urination)

Question 43

what are complications of urinary retention?

Answer 43

- Urinary incontinence - Nocturia (the need to urinate at night) - Hydronephrosis – high pressure in bladder can push urine back up ureters into kidneys. This causes the renal pelvises to expand - Kidney failure - Sepsis - Bladder rupture – retention can lead to anuria (inability to pass urine). This can cause the bladder to stretch and possibly tear

Question 44

describe the ureterorenal reflex

Answer 44

- the ureters are well supplied with pain nerve fibres - when a ureter becomes blocked (eg 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

Question 45

how is micturition affected if there is damage to the brain stem?

Answer 45

- inhibitory signals mostly interrupted - 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 elicit is an uncontrollable micturition reflex, thereby promoting frequent urination

Question 46

what zone of the prostate is response for BPH?

Answer 46

transitional

Question 47

what is the function of the sugars secreted by the prostate?

Answer 47

act as nutrition for sperm

Question 48

testosterone is produced in the testicles, after which it travels to the prostate for what to happen?

Answer 48

converted to dihydrotestosterone (DHT) in the stromal cells by the action of the enzyme type 2 5a-reductase

Question 49

what is the ultimate mediator of prostatic growth and why?

Answer 49

DHT as it causes cell growth and inhibits apoptosis

Question 50

although the ultimate cause of BPH is unknown, it is believed that DHT-induced growth factors act by what?

Answer 50

increasing the proliferation of stromal cells and decreasing the death of epithelial cells

Question 51

during ejaculation, the connection between the bladder and the urethra is what?

Answer 51

closed

Question 52

what do the first changes in BPH involve?

Answer 52

proliferation of glandular tissue in the transitional zone

Question 53

what can androgens do to cause BPH?

Answer 53

increase cellular proliferation and inhibit cell death

Question 54

prostate cancer usually occurs in what zone of the prostate?

Answer 54

peripheral

Question 55

histologically, what is prostate cancer?

Answer 55

adenocarcinoma

Question 56

what is hydronephrosis?

Answer 56

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

Question 57

what may mask the deterioration in renal function associated with ageing in that the serum creatinine may be less than 120mmol/L in a patient with low GFR?

Answer 57

a reduction in muscle mass

Question 58

what is acute renal failure definition?

Answer 58

an abrupt decline in the renal function wiht increased creatinine and increased blood urea nitrogen levels (uraemia) failure of renal excretory function due to depression of the GFR

Question 59

what are Na+ and osmolarity like in renal failure?

Answer 59

decreased Na+ not reabsorbed. the backflow of urine increases the tubular fluid in the kidneys - dilutes the Na+ present in the tubular fluid hence decreasing osmolarity

Question 60

why is K+ raised in renal failure?

Answer 60

renal dysfunction —> person cannot secrete K+ into the tubular fluid (urine) so K+ builds up in cells

Question 61

why is there metabolic acidosis in renal dysfunction?

Answer 61

- kidney unable to secrete H+ ions into the urine - kidney unable to reabsorbed HCO3- from urine

Question 62

why does pCO2 decrease in acute renal failure?

Answer 62

metabolic acidosis so the patient hyperventilates as resp compensation

Question 63

urea and creatinine levels in renal dysfunction?

Answer 63

elevated

Question 64

Hb in renal dysfunction?

Answer 64

drops - because kidneys secrete less erythropoietin

Question 65

what points along the urinary tract are more susceptible to obstruction?

Answer 65

1. pelvic-ureteric junction 2. where the ureters cross the pelvic brim (at the level of the iliac vessels) 3. vesico-ureteric junction

Question 66

describe prostate secretions

Answer 66

thin, mild coloured and alkaline

Question 67

how does insulin treat hyperkalaemia?

Answer 67

insulin stimulates NaH exchanger in GIT — more substrate for NaK ATPase