Physiology of Micturition & Assessment of Renal Function, Urea, Creatinine and GFR

Question 1

When is it important to assess renal function?

Answer 1

Renal disease - rate of decline of GFR gives inication of prognosis - renal disease causes damage to nephrons and therefore reduces nephron function

Many drugs are removed by filtration - excretion decreases when GFR decreases meaning drug concentration in the plasma can reach toxic levels

Question 2

Describe plasma clearance tests

Answer 2

Measure the ability of the plasma to clear various substances

Clearance concerns the volume of plasma cleared and not a quantity of substance removed from the plasma

Question 3

What is the equation for the plasma clearance of X?

Answer 3

Ux = urine concentration of X

V = Urine flow rate

Px = Plasma concentration of X

Question 4

What molecule is often used for plasma clearance tests?

Answer 4

Inulin

In clinical practice, inulin is no longer used, because too cumbersome, 51Cr-EDTA has been used instead, a suitable radioactive substance that is handled by the kidney in the same way as inulin.

Question 5

What makes inulin an effective measurer of GFR?

Answer 5

Freely filtered at the glomerulus

Not reabsorbed or secreted

Not metabolised by the kidney

Doesn’t interfere with normal renal function

Question 6

How does secretion and reabsorption alter clearance rate?

Answer 6

Reabsorbed - lower clearance rate

Secreted - higher clearance rate

Question 7

What is GFR in a normal man

Answer 7

GFR in “normal” man = 125mls/min. The magnitude correlates with surface area, but values in women are » 10% lower, even after correction for surface area. GFR declines by »1ml/min/year after 30

Question 8

GFR is too complex and expensive to measure, it takes several hours and an injection of isotope 51 Cr EDTA - what is the clinical replacement?

Answer 8

Plasma creatinine (a breakdown product of muscle creatine)

Question 9

What is the big caution associated with using creatinine as a marker of GFR?

Answer 9

Plasma creatinine decreases as GFR increases

BUT

It is not a linear equation

The GFR can halve before there is an increase in creatinine

Creatinine plasma concentration is therefore taken into account alongside other variables to make up the estimated GFR

Question 10

What factors affect serum creatinine?

Answer 10

Muscle mass: athletes vs malnutrition

Dietary intake: creatine supplements vs vegetarians

Drugs: Some lead to spurious increases as does ketoacidosis.

Question 11

What is normal GFR?

Answer 11

Normal GFR is approximately 100mls/min/1.73m2

Question 12

What is the clearance of glucose?

Answer 12

0 since it is normally reabsorbed

Question 13

How much urea is reabsorbed?

Answer 13

50%

Question 14

What substance is used to measure real plasma flow (RPF)?

Answer 14

PAH - para-amino-hippuric acid - it is freely filtered at the glomerulus and remaining plasma is secreted. Over 90% of the PAH is removed from the plasma in one transmit of the kidney

Renal plasma flow is about 660 mls/min

Question 15

Answer 15

In this table - when filtration increases reabsorption also increases

When excretion increases - secretion also increases

Question 16

How does urine pass from the kidneys to the bladder?

Answer 16

Urine flows from the kidneys to the ureters via peristaltic contraction of the smooth muscle of the ureters, they enter the bladder at an oblique angle (prevents reflux of urine).

Question 17

What is the muscle of the bladder?

Answer 17

Detrusor muscle

Contraction of this muscle is mainly responsible for emptying the bladder during micturition.

Question 18

Describe the internal urethral sphincter

Answer 18

Not a true sphincter

Where the smooth muscle at the start of the urethra acts as a sphincter when the smooth muscle is relaxed

Question 19

Describe the muscle found in the external sphincter

Answer 19

The external urethral sphincter is a true sphincter, made up of skeletal muscle under voluntary somatic control.

Question 20

What is the bladder overlain with?

Answer 20

Peritoneum

(retroperitoneal)

Question 21

What type of epithelium is found in the bladder?

Answer 21

Transitional epithelium

Question 22

What makes up the trigone of the bladder?

Answer 22

2 vesicoureteric openings

Urethral opening

Question 23

What is normal urine production?

Answer 23

Normal daily urine production varies between 750ml-2500mls in temperate climates.

Question 24

This graph shows the increase in sense of urgency to void as the bladder fills up

Answer 24

There is a long flat segment as the initial increments of urine enter the bladder and then a sudden sharp rise as the micturition reflex is triggered.

Question 25

Which nerves are responsible for contraction of the detrusor muscle?

Answer 25

S2 - S4

Increases the pressure within the bladder

Question 26

How does the hypogastric nerve influence micturition?

Answer 26

Inhibit bladder contraction and closes the internal urethral sphincter

Cutting the hypogastric nerve causes increase in frequency of micturition

Main function is to prevent reflux of semen into the bladder during ejaculation

L1-L3

Question 27

What nerves are associated with the skeletal muscle that forms the external urethral sphincter?

Answer 27

Pudendal nerves - S2 - S4

Question 28

What happens when stretch receptor afferents start increasing discharge to spinal cord via interneurones?

Answer 28

Excitation of parasympathetic outflow

Inhibition of sympathetic outflow

Inhibition of somatic motoneurones to external sphincter

Pathways to sensory cortex - sensation of fullness

Micturition is basically a spinal reflex which may or may not be influenced by higher centres.

Question 29

Why do babies wet themselves?

Answer 29

Micturition reflex serves to stimulate parasympathetic contraction and relaxes the external sphincter by inhibiting somatic motoneurones

Higher brain connections have not been established

This is also the case in adult patients with spinal cord transection after the initial period of spinal shock.

Question 30

What quantitiy of urine in the bladder is enough to initiate the spinal reflex?

Answer 30

300 - 350 mls

Question 31

Which parts of the brain are involved in delay of voiding?

Answer 31

Descending pathways from many brain centres including the cortex and the brainstem

Question 32

What is the effect of descending pathways which cause delay?

Answer 32

inhibit the parasympathetic and:

stimulate the somatic nerves to the external sphincter, thus over-ridding the input from the bladder stretch receptors.

Question 33

What does voluntary inititation involve?

Answer 33

Voluntary initiation involves descending pathways which:

stimulate the parasympathetic and:

inhibit the somatic motor neurones thus summating with the stretch receptor effects.

Question 34

How are pelvic floor muscles involved in micturition?

Answer 34

Relaxation of pelvic floor muscles can cause sufficient downward tug on the setrusor muscle to initiate its contraction

Question 35

What parts of the urinary system can be used to prevent urine flow down the urethra/ interrption of urine flow once urination begins

Answer 35

Perineal muscles and external sphincter can be contracted voluntarily, preventing urine flow flowing down the urethra or interrupting the flow once urination begins.

Question 36

After urination - how does the female and male urethra empty?

Answer 36

Females - by gravity

Males - contractions of the bulbocavernous muscle

Question 37

What are the abnormalities of micturition?

Answer 37

1. Interruption of afferent nerves
2. interruption of both afferent and efferent nerves
3. interruption of facilitatory and inhibitory descending pathways from the brain.

Question 38

What is the result of all the abnormalities of micturition?

Answer 38

In all 3 types the bladder contracts but the contractions are generally insufficient to empty the bladder completely and urine is left in the bladder.

Question 39

Paraplegic patients can pinch/stroke their inner thigh to stimulate voiding - the process is called mild mass reflex - what is the mechanism behind mild mass reflex?

Answer 39

Afferent stimuli irradiate from one reflex centre to another

Noxious stimuli may irradiate to autonimc centres and evoke bladder or rectal voiding