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

Question 1

Important to be able to assess renal function because of its central role in homeostasis. Ability to measure GFR is particularly useful in 2 clinical situations, what are they?

Answer 1

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 indicated by the reduction in GFR

2. Many drugs eg 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 decrease in renal function

Question 2

how do you measure GFR?

Answer 2

Plasma clearance tests are 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 3

what is the calculation used for plasma clearance?

Answer 3

Plasma clearance of X, CX= [UX] V/[PX]

units are mls/min

UX = Urine concentration of X,

V = urine flow rate,

PX = plasma concentration of X

The gold standard is inulin clearance, polyfructose, loading iv dose of inulin, allow time to equilibrate, then sample simultaneously plasma and urine (during a timed urine sample)

Question 4

Inulin is freely filtered at the glomerulus and neither reabsorbed nor secreted. It is not metabolized by the kidney, nor does it interfere with normal renal function so inulin clearance is a measure of GFR

What is the GFR in the following 21 year old male?

UIN = 285 mg/dl

V = 1.1 mls/min

PIN = 2.5 mg/dl

Answer 4

125.4

Question 5

Substances filtered and reabsorbed will have a lower clearance than inulin, why is this?

Answer 5

because [U_X] will be less than if only filtered and [P_X] higher. Substances filtered and secreted will have a higher clearance than inulin because [U_X] will be higher and [P_X] lower

Question 6

what is the normal GFR?

Answer 6

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

Question 7

is inukin used in clinical practice?

Answer 7

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 8

Now considered that GFR is usually too complex and expensive to measure
Takes several hours and requires injection of isotope 51Cr EDTA

what may be used to measure GFR instead?

Answer 8

Creatinine clearance: routinely used to estimate GFR

Creatinine is endogenous (breakdown produce of muscle creatine). Good agreement with inulin clearance

GFR = CIN = CCR

C_CR = [U_CR] V/ [P_CR]

Therefore GFR = 1/[PCR], so plasma creatinine can be used to estimate GFR

Question 9

what are factors tht may affect serum creatinine?

Answer 9

Muscle mass: athletes vs malnutrition

Dietary intake: creatine supplements vs vegetarians

Drugs: Some lead to spurious increases as does ketoacidosis

So: flawed measurement but nevertheless useful

Normal GFR is approximately 100mls/min/1.73m2

ie across range of adults and sexes, for kidney function and size, so may be expressed as a percentage of normal

Question 10

what is the clearance of glucose?

Answer 10

Question 11

what is the clearance of urea?

Answer 11

Question 12

The organic anion para-amino-hippuric acid (PAH) is used to measure real plasma flow (RPF)

it is a carrier of penicillin

what is its clearance?

Answer 12

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 flowing through the kidneys in a given time = renal plasma flow around 660mls/min

Question 13

summary showing renal handling of solutes

Answer 13

Question 14

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

Composition of urine does not _______ once it leaves kidneys

Answer 14

peristaltic

oblique

change

Question 15

Bladder is a bag of smooth muscle, arranged in spiral, longitudinal and circular bundles

what is the msucle called?

Answer 15

detrusor muscle

Question 16

What is the detrusor muscle responsible for?

Answer 16

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

Question 17

WHat are the true and not true sphincters of the urethra?

Answer 17

The internal urethral “sphincter” is 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 18

Describe the anatomy of the bladder

Answer 18

• Overlain with peritoneum
• Lies in midline posterior to pubic bones
• Lies anterior to reproductive system and rectum
• Smooth muscle (Detrusor muscle)
• Lined transitional epithelium

Question 19

what is found in the trigone of the bladder?

Answer 19

2 vesicoureteric openings

Urethral opening

Question 20

what does urethral obstructions lead to?

what does ureter obstructions lead to?

Answer 20

Urethral obstructions = bilateral renal problems

Ureter obstruction = unilateral renal problems

Question 21

Describe the pressure volume curve of the bladder

Answer 21

Pressure-Volume curve of the bladder has a characteristic shape

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

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

Question 22

contorl of mituration - what is the motor innervation?

Answer 22

1. Rich parasympathetic supply (pelvic nerves) ­ increase activity =­ increased contraction of detrusor muscle = increased ­Pressure within the bladder, S2-S4
2. Sparse sympathetic supply (hypogastric nerves), inhibit bladder contraction and closes the internal urethral “sphincter”. (Sympathetic supply is not very important to bladder function but cutting the hypogastric nerve = increased frequency of micturition)

Main function is to prevent reflux of semen into the bladder during ejaculation L1-L3

3. Somatic motoneurones (pudendal nerves), innervate the skeletal muscle that forms the external urethral sphincter, keeps the sphincter closed, even against strong bladder contractions S2-S4

Question 23

what si the sensory innervation of the bladder?

Answer 23

1. Stretch receptor afferents from the bladder wall. As the bladder fills =­ increaed discharge in afferent nerves to spinal cord = via interneurones =
   a) excitation of parasympathetic outflow
   b) inhibition of sympathetic outflow
   c) inhibition of somatic motoneurones to external sphincter
   d) pathways to sensory cortex = sensation of fullness

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

Question 24

Operation of the local spinal reflex:

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

stimulation of the ____________ and:

relax the _________ sphincter by inhibiting the somatic motoneurones

Answer 24

stretch

paraympathetic

external

Question 25

How are babies micturition reflex different?

Answer 25

In “leaky” babies, the micturition reflex operates at this level (spinal cord reflex) because the higher brain connections have to be established. This is also the case in adult patients with spinal cord transection after the initial period of spinal shock

Question 26

In an adult the volume of urine in the bladder required to initiate the spinal reflex is what?

Answer 26

around 300- 350mls

Question 27

Delay is accomplished by descending pathways from many brain centres, including cortex and brainstem, which do what?

Answer 27

inhibit the parasympathetic and:

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

Question 28

Voluntary initiation involves descending pathways which do what?

Answer 28

stimulate the parasympathetic and:

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

Potty training involves the setting up of these controlling pathways

Question 29

One of initial events in voluntary urination is relaxation of the muscles of the pelvic floor and this may cause a sufficient downward tug on the _________ ______ to initiate its contraction

Answer 29

detrusor muscle

Question 30

what muscles can be contractd voluntarily, preventing urine flow flowing down the urethra or interrupting the flow once urination begins

Answer 30

Perineal muscles and external sphincter

Question 31

after urinated in females, what happens to the urethra?

Answer 31

empties by gravity

Question 32

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

Answer 32

bulbocavernosus

Question 33

Abnormalities of Micturition:

3 major types due to neural lesions, waht are they?

Answer 33

1. Interruption of afferent nerves
2. interruption of both afferent and efferent nerves
3. interruption 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 34

The following values were obtained from a 30 year old male patient of normal build:

P_CR = 0.2 mmoles/l

U_CR = 4 mmoles/l

Urine flow rate = 2.5 mls/min

Identify which of the following statements are True or False:

1. Creatinine clearance is 50 mls/min
2. Creatinine clearance is within normal limits
3. Urine flow rate is above normal
4. Plasma creatinine concentration would be expected to increase if creatinine clearance increased

Answer 34

F

F

F

F