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

Question 1

What are two cases when testing GFR is particularly useful clinically?

Answer 1

1. In patients with renal disease there can be nephron destruction, total GFR = sum of filtration by all functioning nephrons - disease would lower GFR
2. Many drugs removed by filtration, if filtration (GFR) is decreased plasma [drug] will increase so may need to adjust the dose

Question 2

What does plasma clearance refer to?

Answer 2

Volume of plasma cleared of toxins

not the quantity of urine / quantity of substances removed from plasma

Question 3

What is the formula for plasma clearance?

Answer 3

C = UV / P

C = clearance 
U = urine concentration of substance 
V = Urine flow rate 
P = Plasma concentration of substance

Question 4

What is the gold standard for obtaining the values needed to calculate plasma clearance?

Answer 4

• Inulin (polyfructose) clearance

- Loading dose of IV inulin, time to equilibrate, sample simultaneously plasma and urine

Question 5

Why is inulin the ideal molecule for testing plasma clearance?

Answer 5

Because it is freely filtered at the glomerulus and neither reabsorbed nor secreted

Question 6

How do reabsorption and secretion affect the clearance of a molecule?

Answer 6

• Reabsorption lowers clearance because it lowers U and raises P
• Secretion raises clearance because it increases U and lowers P

Question 7

How does the GFR for men and women compare? What is the normal GFR in man? How does GFR change with age?

Answer 7

• GFR is about 10% lower in women
• GFR = 125 mLs/min
• GFR decreases by about 1mL/min/year after 30

Question 8

Inulin is no longer used in clinical practice to test GFR, what is?

Answer 8

51Cr-EDTA

Question 9

Accurate GFR testing isn’t usually done in practice anymore due to complexity and cost, what is?

Answer 9

• estimated GFR testing (eGFR)
• Uses creatinine
• apparently C = 1 / P for creatinine

Question 10

Is plasma creatinine a good detector of early stage renal disease?

Answer 10

• No because plasma creatinine is not linear with GFR, has a non-linear relationship
• Can halve GFR before seeing plasma creatinine rise
• Apparently there are formulae which take these confounding variables Into account

Question 11

What are some factors that can affect serum creatinine?

Answer 11

• Amount of muscle mass
• Dietary intake (creatine supps vs. vegetarians)
• Drugs / DKA

Question 12

What is measured to determine real plasma flow (RPF) at the kidneys? Why?

Answer 12

• para-amino-hippuric acid (PAH) is used to measure plasma flow
• PAH is freely filtered and actively secreted so that >90% of plasma is cleared of its PAH in one go at the kidney. Therefore good measure of real plasma flow

Question 13

How can you determine if a substance is reabsorbed or secreted in the tubules?

Answer 13

• Clearance, is its clearance higher or lower than that of inulin?

Question 14

Is urine flow from the kidneys to the bladder passive?

Answer 14

No, there is peristaltic action at the smooth muscle of the ureters

Question 15

What is the detrusor muscle? Function?

Answer 15

The smooth muscle found in the wall of the bladder, rranged in spiral, longitudinal and circular bundles

• Contraction of this muscle is empties the bladder during micturition

Question 16

Describe the internal urethral sphincter

Answer 16

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

Question 17

Describe the external urethral sphincter

Answer 17

True sphincter made of skeletal muscle under voluntary control

Question 18

what makes up the trigone of the bladder?

Answer 18

• 2 vesicouteric openings

- 1 Urethral opening

Question 19

How is the pressure-volume curve of the bladder shaped?

Answer 19

Hockey stick shape

• Got a long flat pressure section as the bladder begins to fill, then a sudden sharp increase as a certain volume is reached and the micturition reflex is triggered

Question 20

What nerves innervate the detrusor muscle?

Answer 20

• Parasympathetic pelvic nerves (S2-S4): cause contraction and pressure increase during micturition
• Sympathetic supply from hypogastric nerves: inhibit bladder contraction and close internal sphincter. L1-L3 symp. nerves prevent reflux of semen into bladder

Question 21

What nerve innervates the external urethral sphincter?

Answer 21

Somatic motor neurones: pudendal nerves (S2-S4)

Question 22

Describe the sensory innervation of the bladder as the bladder fills

Answer 22

Stretch afferents send signals to the spinal cord, via interneurones:

• excitation of parasympathetic outflow
• Inhibition of sympathetic outflow
• Inhibition of somatic motoneurones
• Sensation of fullness to sensory cortex

Question 23

Describe the control of micturition

Answer 23

Basically a spinal reflex that may or may not be influenced by higher centres

Question 24

What is the volume of urine needed to activate the spinal reflex in adults?

Answer 24

300-350 mL

Question 25

How is delay of micturition accomplished via innervation?

Answer 25

Higher centres:

• Inhibit parasympathetic input to bladder
• Stimulate somatic nerves to external sphincter

Initiation does the opposite

Question 26

How does the urethra empty?

Answer 26

• Via gravity in females

- Via constriction of the bulbocavernosus muscle in males

Question 27

What are the three major neural lesions that can affect micturition?

Answer 27

1. Interruption of afferent nerves
2. Interruption of afferent and efferent nerves
3. Interruption of descending pathways from the brain

Usually result in contraction that is insufficient at emptying the bladder