Physiology of Micturition and Assessment of Renal Function

Question 1

Why is it important to be bale to assess renal function?

Answer 1

Due to its central role in homeostasis

Question 2

In what clinical situations is it particularly useful to be able to measure GFR?

Answer 2

In patients with renal disease

• progression of the underlying disease process results in nephron destruction and decreased nephron function
• total GFR = sum of all filtration by functioning nephrons, so the progression of disease would be indicated by reduction of GFR

Many drugs e.g. digitalis and antibiotics are removed from the body by excretion and filtration
- when GFR falls, excretion falls so that [drug] in plasma may rise causing toxicity and the need to adjust the dose, appropriate to the reduced renal function

Question 3

What tests are used to measure renal function?

Answer 3

Plasma clearance tests - measure the ability of the kidney to clear the plasma of various substances

Question 4

What does plasma clearance relate to?

Answer 4

A volume of plasma cleared, not a quantity of substance removed from the plasma

Question 5

What is the equation used to calculate the plasma clearance of a substance X?

Answer 5

Plasma clearance of X = Cx

Cx = [Ux] V / Px

Where:
Ux = urine concentration of X
V = urine flow rate
Px = plasma concentration of X

Question 6

How can plasma inulin clearance be measured?

Answer 6

Give polyfructose and loading IV dose of inulin, allow time to equilibrate then sample simultaneously the plasma and urine (during a timed urine sample)

Question 7

How is inulin filtered?

Answer 7

Freely filtered at the glomerulus, and is neither reabsorbed or secreted

Question 8

Why can inulin clearance be used as a measurement of GFR?

Answer 8

It is not metabolised by the kidney and it does not interfere with normal renal function so its clearance can be used as a measurement of GFR

Question 9

Why will substances which are filtered and reabsorbed have a lower clearance than inulin?

Answer 9

Because [Ux] will be less than it would if it was only filtered, and [Px] will be higher
Substances filtered and secreted will have a higher clearance than inulin because [Ux] will be higher and [Px] lower

Question 10

What is GFR in a normal male?

Answer 10

125 ml/min

Question 11

What does magnitude correlate with?

Answer 11

Surface area

Question 12

After what age does GFR decline?

Answer 12

GFR declines by around 1ml/min/year after age 30

Question 13

How is GFR measured in clinical practice?

Answer 13

Inulin is no longer used - injection of isotope 51Cr-EDTA is used

Question 14

GFR is considered too complex and expensive to measure, what is routinely measured instead?

Answer 14

Creatinine clearance is now routinely used to estimate GFR as it is endogenous and shows good agreement with inulin clearance

Question 15

What are the factors affecting serum creatinine?

Answer 15

Muscle mass - athletes, malnutrition
Dietary intake - creatine supplements, vegetarians
Drugs - some lead to spurious increase

Question 16

Why does glucose have a clearance of zero?

Answer 16

Because normally all of it is reabsorbed

Question 17

Why is clearance of urea less than that of inulin?

Answer 17

Because some urea is reabsorbed

Question 18

Why does penicillin have a greater clearance than inulin?

Answer 18

Because it is filtered and secreted

Question 19

For any molecule, X, that is freely filtered at the glomerulus, when is filtration greater than excretion?

Answer 19

When renal handling of X is net reabsorption of X

Question 20

For any molecule, X, that is freely filtered at the glomerulus, when is excretion greater than filtration?

Answer 20

When renal handling of X is net secretion of X

Question 21

For any molecule, X, that is freely filtered at the glomerulus, when are filtration and excretion the same?

Answer 21

When there is no net reabsorption or secretion

Question 22

For any molecule, X, that is freely filtered at the glomerulus, when is clearance of X less than inulin clearance?

Answer 22

When renal handling of X is net reabsorption of X

Question 23

For any molecule, X, that is freely filtered at the glomerulus, when is clearance X equal to inulin clearance?

Answer 23

When X is neither reabsorbed nor secreted

Question 24

For any molecule, X, that is freely filtered at the glomerulus, when is clearance of X greater than inulin clearance?

Answer 24

When renal handling of X is net secretion of X

Question 25

How does urine flow from the kidneys to the ureters?

Answer 25

Via peristaltic contraction of the smooth muscle of the ureters

Question 26

How do the ureters enter the bladder?

Answer 26

Enter at an oblique angle, to prevent reflux of urine

Question 27

When does the composition of urine not change?

Answer 27

Once it leaves the kidneys

Question 28

How is the smooth muscle of the bladder arranged?

Answer 28

In spiral, longitudinal and circular bundles

Question 29

What muscle is responsible for emptying the bladder?

Answer 29

Contraction of the detrusor muscle

Question 30

What is the internal urethral sphincter?

Answer 30

Not a true sphincter - but is where the smooth muscle at the start of the urethra acts as a sphincter when the smooth muscle is relaxed

Question 31

What is the external urethral sphincter?

Answer 31

True sphincter - composed of skeletal muscle, and is under voluntary control

Question 32

What is the anatomical position of the bladder?

Answer 32

Lies in the midline, posterior to the pubic bones

Lies anterior to the reproductive system and the rectum

Question 33

What type of epithelium lines the bladder?

Answer 33

Transitional epithelium

Question 34

What problems are caused by urethral obstruction and ureter obstruction?

Answer 34

Urethral obstruction causes bilateral renal problems, while ureter obstruction causes unilateral renal problems

Question 35

What is the characteristic shape of the pressure-volume curve?

Answer 35

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 36

What is the normal variation in daily urine production?

Answer 36

Between 750ml-2500ml

Question 37

What is the effect of motor parasympathetic innervation of the bladder?

Answer 37

Rich parasympathetic supply increases activity and increases contraction of the detrusor muscle which results in increased pressure within the bladder

Question 38

What is the effect of motor sympathetic innervation of the bladder?

Answer 38

Sparse sympathetic supply inhibits bladder contraction and closes the internal urethral sphincter

Question 39

What is the function of somatic motoneurons innervating the bladder?

Answer 39

Innervate the skeletal muscle that forms the external urethral sphincter and keeps it closed, even against strong bladder contractions

Question 40

What is the sensory innervation of the bladder?

Answer 40

Stretch receptor afferents from the bladder wall
As bladder fills, there is increased discharge in afferent nerves to the spinal cord via interneurones causing:
- excitation of parasympathetic outflow
- inhibition of sympathetic outflow
- inhibition of somatic motoneurons to external sphincter

Question 41

What is stimulated as the bladder fills?

Answer 41

Stretch receptors are increasingly stimulated until their output becomes great enough to cause bladder contraction via stimulation of the parasympathetic nerves and relaxation of the external sphincter by inhibiting somatic motoneurons

Question 42

In adults, what is the volume of urine in the bladder required to initiate the spinal reflex?

Answer 42

Around 300-350ml

Question 43

How is delay in micturition accomplished?

Answer 43

By the descending pathways from many centres, including the brainstem and cortex, these inhibit the parasympathetic nerves and stimulate the somatic nerves to the external sphincter, over-riding the input from the bladder stretch receptors

Question 44

What pathways are involved in voluntary initiation of micturition?

Answer 44

Descending pathways which stimulate the parasympathetic nerves and inhibit the somatic motor neurones, thus summating with the stretch receptor effects

Question 45

What is the initial event in voluntary urination?

Answer 45

Relaxation of the muscles of the pelvic floor, which may cause a sufficient downward tug on the detrusor muscle to initiate its contraction

Question 46

What muscles can be contracted voluntarily in micturition?

Answer 46

Perineal muscles and external sphincter

Question 47

What does voluntary contraction of the perineal muscles and external sphincter prevent?

Answer 47

Urine from flowing down the urethra or interrupting the flow once urination begins

Question 48

How does the urethra empty after urination?

Answer 48

Empties by gravity in females

Empties by contractions of the bulbocavernosus muscle in males

Question 49

What are the 3 major types of neural lesions which result in abnormalities of micturition?

Answer 49

Interruption of afferent nerves
Interruption of both afferent and efferent nerves
Interruption of facilitatory and inhibitory descending pathways from the brain

In all three types, the bladder contracts but the contractions are generally insufficient to empty the bladder completely, so urine is the left in the bladder

Question 50

How might paraplegic patients train themselves to initiate voiding?

Answer 50

By pinching or stroking thighs to cause mild mass reflux

Question 51

After a spinal section, afferent stimuli irradiate from

Answer 51

one reflex centre to another

Question 52

What effect might a relatively minor noxious stimuli have on micturition when applied to the skin?

Answer 52

It may irradiate to autonomic centres and evoke bladder or rectal voiding

This returns some measure of voluntary control by allowing them to induce an intentional mass reflux