Physiology of Micturition & Assessment of Renal Function, Urea, Creatinine and GFR Flashcards
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?
- 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
- 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
how do you measure GFR?
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
what is the calculation used for plasma clearance?
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)
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
125.4
Substances filtered and reabsorbed will have a lower clearance than inulin, why is this?
because [UX] will be less than if only filtered and [PX] higher. Substances filtered and secreted will have a higher clearance than inulin because [UX] will be higher and [PX] lower
what is the normal GFR?
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
is inukin used in clinical practice?
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
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?
Creatinine clearance: routinely used to estimate GFR
Creatinine is endogenous (breakdown produce of muscle creatine). Good agreement with inulin clearance
GFR = CIN = CCR
CCR = [UCR] V/ [PCR]
Therefore GFR = 1/[PCR], so plasma creatinine can be used to estimate GFR
what are factors tht may affect serum creatinine?
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
what is the clearance of glucose?
what is the clearance of urea?
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?
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
summary showing renal handling of solutes
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
peristaltic
oblique
change
Bladder is a bag of smooth muscle, arranged in spiral, longitudinal and circular bundles
what is the msucle called?
detrusor muscle
What is the detrusor muscle responsible for?
Contraction of this muscle is mainly responsible for emptying the bladder during micturition
WHat are the true and not true sphincters of the urethra?
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
Describe the anatomy of the bladder
- Overlain with peritoneum
- Lies in midline posterior to pubic bones
- Lies anterior to reproductive system and rectum
- Smooth muscle (Detrusor muscle)
- Lined transitional epithelium
what is found in the trigone of the bladder?
2 vesicoureteric openings
Urethral opening
what does urethral obstructions lead to?
what does ureter obstructions lead to?
Urethral obstructions = bilateral renal problems
Ureter obstruction = unilateral renal problems
Describe the pressure volume curve of the bladder
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
contorl of mituration - what is the motor innervation?
- Rich parasympathetic supply (pelvic nerves) increase activity = increased contraction of detrusor muscle = increased Pressure within the bladder, S2-S4
- 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
- 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
what si the sensory innervation of the bladder?
- 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.
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
stretch
paraympathetic
external
How are babies micturition reflex different?
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
In an adult the volume of urine in the bladder required to initiate the spinal reflex is what?
around 300- 350mls
Delay is accomplished by descending pathways from many brain centres, including cortex and brainstem, which do what?
inhibit the parasympathetic and:
stimulate the somatic nerves to the external sphincter, thus over-ridding the input from the bladder stretch receptors
Voluntary initiation involves descending pathways which do what?
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
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
detrusor muscle
what muscles can be contractd voluntarily, preventing urine flow flowing down the urethra or interrupting the flow once urination begins
Perineal muscles and external sphincter
after urinated in females, what happens to the urethra?
empties by gravity
Urine remaining in the male urethra is expelled by contractions of the _____________ muscle
bulbocavernosus
Abnormalities of Micturition:
3 major types due to neural lesions, waht are they?
- Interruption of afferent nerves
- interruption of both afferent and efferent nerves
- 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
The following values were obtained from a 30 year old male patient of normal build:
PCR = 0.2 mmoles/l
UCR = 4 mmoles/l
Urine flow rate = 2.5 mls/min
Identify which of the following statements are True or False:
- Creatinine clearance is 50 mls/min
- Creatinine clearance is within normal limits
- Urine flow rate is above normal
- Plasma creatinine concentration would be expected to increase if creatinine clearance increased
F
F
F
F
