Physiology of Micturition & Assessment of Renal Function, Urea, Creatinine and GFR Flashcards
Why is ability to measure GFR particularly useful in patients with renal disease?
Total GFR = sum of all filtration by functioning nephrons so progression of disease would be indicated by the reduction in GFR
Why is measuring GFR particularly useful in drug dosing?
Many drugs e.g. digitalis and many abx 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
What do plasma clearance tests measure?
The ability of the kidney to clear the plasma of various substances (it is the plasma that is important NOT the urine)
What does clearance relate to?
A volume of plasma cleared
(NOT a quantity of substance removed from the plasma)
Give the equation used to work out plasma clearance of X
CX = [UX] V/[PX]
units mls/min
Give the meaning for each of the components of CX = [UX] V/[PX]
UX = urine concentration of X
V = urine flow rate
PX = plasma concentration of X
What is the gold standard for clearance? What is`the process of testing?
INULIN CLEARANCE (polyfructose)
Loading IV dose of inulin, allow time to equilibriate, then sample simultaneously plasma and urine (during a timed urine sample)
Diagram of 100% inulin clearance
How is inulin a good measure of GFR?
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
= MEASURE OF GFR
What happens to substances that have a LOWER clearance than inulin?
Substances are filtered and reabsorbed
Because [UX] will be less than if only filtered and [PX] higher
What happens to substances that have a HIGHER clearance than inulin?
They will be filtered and secreted
Because [UX] will be higher and [PX] lower
What is the GFR in a normal man?
125ml/min
Magnitude of GFR correlates with surface area; even with correction for surface area, are GFR values in women equal or different to men?
Values in women are ~10% lower
(~112.5)
After the age of 30 how much does GFR decline by per year?
~1ml/min/year
Work out the GFR in a 21 yr old male with UIN = 285mg/dl, V = 1.1ml/min, PIN = 2.5mg/dl
125.4 GFR
Diagram showing: insulin and normal GFR; lower clearance substances reabsorbed; higher clearance substances secreted
In clinical practice inulin is no longer used, because too cumbersome, so what is used instead?
51Cr-EDTA
What is 51Cr-EDTA?
A radioactive substance that is handled by the kidney in the same way as inulin
GFR is now considered too complex and expensive to measure - takes several hrs and requires 51Cr-EDTA injection - what is now routinely used to estimate GFR instead?
CREATININE CLEARANCE !
Give the rationale for using creatinine instead of insulin to measure GFR
GFR = CIN = CCR
CCR = [UCR] V/ [PCR]
therefore GFR inversely proportional to 1/ [PCR]
so plasma creatinine can be used to estimate GFR
Is the relationship between GFR and creatinine described as linear?
NO!
GFR can halve before PCR elevates (if it was linear - halving of GFR would cause doubling of PCR)
Give 3 factors affecting serum creatinine
What does this mean for the measurement of GFR?
Muscle mass: athletes vs malnutrition
Dietary intake: creatinine supplements vs vegetarians
Drugs: some lead to spurious increases as does ketoacidosis
Flawed measurement but nevertheless useful
What is approximate normal GFR in mls/min/1.73m2?
100
(i.e. across range of adults and sexes, for kidney function and size, so may be expressed as a percentage of normal)
There are formulae using serum creatinine value which can take into account confounding variables; what can we find with these formulae?
estimated GFR (eGFR)
What is the clearance of glucose?
ZERO ! (all is normally reabsorbed)
What is the clearance of urea compared to that of inulin? Why?
Clearance of urea is less than that of inulin because some urea is reabsorbed
What is PAH?
An organic anion
Para-amino-hippuric acid (PAH)
What is PAH used to measure?
Renal plasma flow (RPF)
How is PAH filtered? How much of plasma is cleared of its PAH content in one transit of the kidney?
It 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
PAH clearance is therefore a measure of all the plasma flowing through the kidneys in a given time; what is the approximate normal renal plasma flow?
~660mls/min
What is the clearance of penicillin compared with inulin?
Penicillin has a greater clearance than inulin because filtered and secreted
Table summarising renal handling of solutes for any molecule X that is freely filtered at the glomerulus
How does urine flow from the kidneys to the ureters?
Via peristaltic contraction of the smooth muscle of the ureters
(then enters bladder at an oblique angle to prevent reflux of urine)
Does the composition of urine change once it leaves the kidneys?
Nope
How is the structure of the bladder described?
‘A bag of smooth muscle’, arranged in spiral, longitudinal and circular bundles = detrusor muscle
What is the detrusor muscle mainly responsible for?
The emptying of the bladder during micturition
The internal urethral sphincter is NOT a true sphincter, what is it?
Where the smooth muscle at the start of the urethra acts as a sphincter when the smooth muscle is relaxed
Is the external urethral sphincter a true sphincter?
YES; made up of skeletal muscle under voluntary somatic control
Describe the anatomical position of the bladder
- Lies in midline posterior to pubic bones
- Lies anterior to reproductive system and rectum
What type of muscle and epithelium is the bladder made up of?
Smooth muscle (detrusor muscle)
Lined transitiona epithelium
What are the 1-2cm oblique passages through the muscular wall of bladder form ureter called?
Vesicoureteric openings
What is the ‘trigone’ of the bladder?
- 2 vesicoureteric openings
- Urethral opening
Does urethral obstruction lead to unilateral or bilateral renal problems?
Bilateral renal problems
Does ureter obstruction lead to bilateral or unilateral renal problems?
Unilateral renal problems
What is the characteristic shape of the pressure-volume curve of the bladder?
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
Graph of cystometrogram showing pressure-volume curve
Motor supply of bladder consists of:
- Rich parasympathetic supply - pelvic nerves S2-S4
- Sparse sympathetic supply - hypogastric nerves L1-L3
- Somatic motoneurones - pudendal nerves S2-S4
Describe the function of the parasympathetic supply to the bladder
When activity is increase = contraction of detrusor muscle (starts of micturition process) = increases pressure within bladder
Describe the function of the sympathetic supply to the bladder
Inhibits bladder contraction and closes the internal urethral ‘sphincter’
(not v important for bladder function but if u cut the hypogastric nerve = increased frequency of micturition; main function is to prevent reflux of semen into bladder during ejaculation)
Describe the function of the somatic motoneurones innervating the bladder
Innervate the skeletal muscle that forms the external urethral sphincter, keeps the sphincter closed, even against storng bladder contractions
What is the sensory innervation to the bladder wall?
Stretch receptor afferents from the bladder wall
Describe the function of the sensory innervation of the bladder via stretch receptors
As bladder fills = increased dischage in afferent nerves to spinal cord -> via interneurones:
- Excitation of parasympathetic flow
- Inhibition of sympathetic flow
- Inhibition of somatic motoneurones to external sphincter
- Pathways to sensory cortex -> sensation of fullness
(micturition is basically a spinal reflex which may or may not be influenced by higher centres)
Bladder at rest
Bladder during micturition
Describe operation of the local spinal reflex
As bladder fills, it becomes distended and stretch receptors are increasingly stimulated until their output becomes great enough to cause bladder contraction via stimulation of parasympathetic and relax the external sphincter by inhibiting somatic motoneurones
In ‘leaky’ babies, why does the micturition reflex operate at the level of the local spinal reflex?
Because the higher brain connections still have to be established
Also the case in adult patients with spinal cord transection after the initial period of spinal shock
In an adult what is the volume of urine in the bladder required to initiate the spinal reflex?
~300-350mls
Summary control of micturition
How is delay of micturition accomplished?
By descending pathways from many brain centres, inc cortex and brainstem
What do the descending pathways from e.g. cortex and brainstem do to accomplish delay of micturition?
Inhibit the parasympathetic and stimulate somatic nerves of external sphincter = overrides input from bladder strecth receptors
How is volunatary initiation of micturition accomplished?
Involves descending pathways which stimulate the parasymaptehtic and inhibit somatic motor neurones thus summating the stretch receptor effects
(potty training = setting up these pathways)
How do the muscles of the pelvic floor play a role in voluntary urination?
Relaxation of muscle of pelvic floor is one of the initial events of voluntary initiation - this may cause a sufficient downward tug on detrusor muscle to initiate its contraction
What can be contracted voluntarily to prevent urine flow down the urethra/interrupt flow once urination begins?
Perineal muscles and external sphincter
How is remaining urine expelled in males vs females after urination?
Female urethra empties by gravity
Urine remaining in male urethra is expelled by contractions of the bulbocavernosus muscle
What are the 3 major types of abnormality of micturition due to neural lesions?
- 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 of micturition abnormalities due to neural lesions, what happens?
The bladder contracts but the contractions are generally insufficient to empty the bladder completely and urine is left in the bladder
Control of micturition diagram w delay and initiation
What is the mild mass reflex?
Used in some paraplegic patients to train themselves to initiate voiding by pinching or stroking their thighs
