Renal Assessmemt and Micturition

Question 1

Why do we need to assess renal function?

Answer 1

Central role in homeostasis

Question 2

The ability to measure GFR is particularly useful in 2 clinical situations.

What are they?

Answer 2

1. 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 progression of disease would be indicate by the reduction in GFR.

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

Question 3

What is plasma clearance?

Answer 3

Plasma clearance tests used to measure renal function.

They measure the ability of the kidney to clear the plasma of various substances.

N.B. It is the plasma that is important NOT the urine
Clearance relates to a volume of plasma cleared NOT a quantity of substance removed from the plasma.

Question 4

What is the gold standard of plasma clearance tests?

Answer 4

Inulin clearance, polyfructose,

Loading IV dose of inulin
Allow time to equilibrate
Sample simultaneously plasma and urine (during a timed urine sample)

Question 5

Why is inulin so good for measuring plasma clearance?

Answer 5

Freely filtered at the glomerulus and neither reabsorbed nor secreted.

It is not metabolised by the kidney, nor does it interfere with normal renal function.

Inulin clearance is therefore a great measure of GFR

Question 6

How will the clearance of a substance that is filtered and reabsorbed compare to the clearance of inulin?

Answer 6

Lower clearance

Question 7

How will the clearance of a substance filtered and secreted compare to inulin?

Answer 7

Highre clearance

Question 8

What is the normal GFR?

Answer 8

“Normal” man = 125mls/min

The magnitude correlates with surface area, but values in women are around 10% lower, even after correction for surface area.

Question 9

How does GFR decline as you age?

Answer 9

Declines by around 1ml/min/year after 30

Question 10

What is the equation for measuring clearance?

Answer 10

Cx = [Ux] V/[Px]

Ux = Urine concentration of x

V = urine flow rate

Px = plasma concentration of x

Question 11

Why is inulin clearance no longer used in clinical practice?

Explain the use of 51Cr-EDTA

Answer 11

Too cumbersome, 51Cr-EDTA has been used instead, a suitable radioactive substance that is handled by the kidney in the same way as inulin.

Now it is considered that GFR is usually too complex and expensive to measure

Takes several hours and requires injection of isotope 51Cr-EDTA.

Question 12

What plasma clearance test is used more nowadays?

Answer 12

Creatinine clearance routinely used to estimate GFR.

Creatinine is endogenous (breakdown produce of muscle creatine).

Good agreement with inulin clearance…

Question 13

Why is creatinine clearance very much an estimate of GFR?

How do we get around this?

Answer 13

We would expect a linear relationship between plasma creatinine and GFR but this is not true.

We can half the GFR before there is any elevation in plasma creatinine levels.

There are formulae using serum creatinine value which can take into account confounding variables.

Using these formulae can estimate GFR
Writen as eGFR (estimated GFR)

Question 14

What factors affect serum creatinine?

Answer 14

Muscle mass: athletes vs malnutrition

Dietary intake: creatine supplements vs vegetarians

Drugs: some lead to spurious increases as does ketoacidosis

Question 15

What is the clearance of glucose in health?

Answer 15

0 because normally its all reabsorbed

Question 16

How does the learance of urea compare to inulin?

Answer 16

Less than inulin because some urea is reabsorbed

Question 17

What is PAH clearance?

What is it used to measure and how can it do this?

Answer 17

The organic anion Para-Amino- Hippuric acid (PAH) is used to measure renal plasma flow (RPF)

PAH is freely filtered at the glomerulus and then the PAH remaining in the plasma is actively secreted into the tubule so that >90% of plasma is cleared of its PAH content in one transit of the kidney.

Therefore PAH clearance is a measure of all the plasma flowwing through the kidneys in a given time = renal plasma flow around 660mls/min

Question 18

How does the clearance of penicillin compare to the clearance of inulin?

Answer 18

Greater clearance than inulin because its filtered and secreted

Question 19

How does urine flow from the kidneys to the bladder?

Answer 19

Via ureters

Peristaltic movement of the ureters, they enter the blade at an oblique angle

Question 20

How does the composition of the urine change once it leaves the kidney?

Answer 20

It doesn’t

Question 21

How does the internal urethral sphincter compare to the external urethral sphicter?

Answer 21

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

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

Question 22

What is the characteristic shape of the Pressure-Volume curve of the bladder?

Answer 22

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 23

Describe the motor innervation of the bladder what helps in control of micturition

Answer 23

1. Rish parasympathetic supply (pelvic nerves) Increase activity -> increase contraction of detrusor muscle -> increase pressure within the bladder
2. Sparse sympathetic supply (hypogalstric nerves), inhibit bladder contraction and closes the internal urethral “sphincter”.
3. Somatic motoneurones (pudendal nerves), innervate the skeletal muscle that forms the external urethral sphincter, keeps the pshincter closed, even against strong bladder contractions

Question 24

What spinal nerves control parasympathetic nerve supply to detrusor of bladder?

Answer 24

S2-S4

Question 25

What effect does cutting the hypogastric nerve have on micturition?

Answer 25

Sympathetic supply is not very important to bladder function but cutting the hypogastric nerve -> Increased frequency of micturition

Question 26

What is the main function of the sympathetic system in bladder control?

Answer 26

Prevent reflux of semen into the bladder during ejactulation

L1-L3

Question 27

What spinal nerves carry somatic motoneurones that keeps the external sphincter closed when we dont want to pee?

Answer 27

S2-S4

Question 28

Describe the sensory innervation of the bladder

Answer 28

1. Stretch receptor afferents from the bladder wall.
   As the bladder fills -> increased discharge in afferent nerves to spinal cord -> Via interneurones ->

• Excitation of parasympathetic outflow
• Inhibition of sympathetic outflow
• Inhibition of somatic motoneurones to external sphincter
• pathways to sensory cortex -> sensation of fullness

Question 29

How is micturition controlled at its very simplest?

Answer 29

Basically a spinal reflex which may or may not be influences by higher centres

Question 30

How does the operation of the local spinal reflex work?

Answer 30

As the bladder fills, it becomes distended and the stretch receptors are increasingly stimulated, until their output becomes great enough to cause bladder contraction via:

• Stimulation of the parasympathetic
• Relaxation of external sphincter by inhibiting somatic motoneurones.

Question 31

Why do babies “leak”?

Answer 31

The micturition reflex operates at the spinal level because the higher brain connections have yet to be established.

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

Question 32

How is delay in micturition achieved?

Answer 32

Descending pathways from many brain centres, including cortex and brainstem, which:

-Inhibit the parasympathetic and stimulate the somatic nerves to the external sphincter, thus overridding the input from the bladder stretch receptors.

Question 33

What is one of the initial events in voluntary urination which may cause a sufficient downwards tug on the detrusor muscle to initiate its contraction?

Answer 33

Relaxation of the muscles of the pelvic floor

Question 34

What muscles can be contracted voluntarily, preventing urine flow flowing down the urethra or interupting the flow once urination begins?

Answer 34

Perineal muscles and external sphincter

Question 35

After urination how does the male and female urethra empty?

Answer 35

After urination, female urethra empties by gravity

Urine remaining in the male urethra is expelled by contractions of the bulbocavernosus muscle

Question 36

What 3 major types of abnormalities of micturition are due to neural lesions?

Answer 36

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

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 37

how can some paraplegic patients train themselves to initiate voiding?

Answer 37

Pinching or stroking their thighs -> mild mass reflex

After spinal section, afferent stimuli irradiate from one reflex centre to another.

When a relatively minor noxious stimulus is applied to the skin it may irradiate to autonomic centres and evoke bladder or rectal voiding.

Returns some measure of “voluntary” control by allowing them to induce an intentional mass reflex