When is it important to assess renal function?
Renal disease - rate of decline of GFR gives inication of prognosis - renal disease causes damage to nephrons and therefore reduces nephron function
Many drugs are removed by filtration - excretion decreases when GFR decreases meaning drug concentration in the plasma can reach toxic levels
Describe plasma clearance tests
Measure the ability of the plasma to clear various substances
Clearance concerns the volume of plasma cleared and not a quantity of substance removed from the plasma
What is the equation for the plasma clearance of X?
Ux = urine concentration of X
V = Urine flow rate
Px = Plasma concentration of X
What molecule is often used for plasma clearance tests?
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.
What makes inulin an effective measurer of GFR?
Freely filtered at the glomerulus
Not reabsorbed or secreted
Not metabolised by the kidney
Doesn't interfere with normal renal function
How does secretion and reabsorption alter clearance rate?
Reabsorbed - lower clearance rate
Secreted - higher clearance rate
What is GFR in a normal man
GFR in “normal” man = 125mls/min. The magnitude correlates with surface area, but values in women are » 10% lower, even after correction for surface area. GFR declines by »1ml/min/year after 30
GFR is too complex and expensive to measure, it takes several hours and an injection of isotope 51 Cr EDTA - what is the clinical replacement?
Plasma creatinine (a breakdown product of muscle creatine)
What is the big caution associated with using creatinine as a marker of GFR?
Plasma creatinine decreases as GFR increases
It is not a linear equation
The GFR can halve before there is an increase in creatinine
Creatinine plasma concentration is therefore taken into account alongside other variables to make up the estimated GFR
What factors affect serum creatinine?
Muscle mass: athletes vs malnutrition
Dietary intake: creatine supplements vs vegetarians
Drugs: Some lead to spurious increases as does ketoacidosis.
What is normal GFR?
Normal GFR is approximately 100mls/min/1.73m2
What is the clearance of glucose?
0 since it is normally reabsorbed
How much urea is reabsorbed?
What substance is used to measure real plasma flow (RPF)?
PAH - para-amino-hippuric acid - it is freely filtered at the glomerulus and remaining plasma is secreted. Over 90% of the PAH is removed from the plasma in one transmit of the kidney
Renal plasma flow is about 660 mls/min
In this table - when filtration increases reabsorption also increases
When excretion increases - secretion also increases
How does urine pass from the kidneys to the bladder?
Urine flows from the kidneys to the ureters via peristaltic contraction of the smooth muscle of the ureters, they enter the bladder at an oblique angle (prevents reflux of urine).
What is the muscle of the bladder?
Contraction of this muscle is mainly responsible for emptying the bladder during micturition.
Describe the internal urethral sphincter
Not a true sphincter
Where the smooth muscle at the start of the urethra acts as a sphincter when the smooth muscle is relaxed
Describe the muscle found in the external sphincter
The external urethral sphincter is a true sphincter, made up of skeletal muscle under voluntary somatic control.
What is the bladder overlain with?
What type of epithelium is found in the bladder?
What makes up the trigone of the bladder?
2 vesicoureteric openings
What is normal urine production?
Normal daily urine production varies between 750ml-2500mls in temperate climates.
This graph shows the increase in sense of urgency to void as the bladder fills up
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.
Which nerves are responsible for contraction of the detrusor muscle?
S2 - S4
Increases the pressure within the bladder
How does the hypogastric nerve influence micturition?
Inhibit bladder contraction and closes the internal urethral sphincter
Cutting the hypogastric nerve causes increase in frequency of micturition
Main function is to prevent reflux of semen into the bladder during ejaculation
What nerves are associated with the skeletal muscle that forms the external urethral sphincter?
Pudendal nerves - S2 - S4
What happens when stretch receptor afferents start increasing discharge 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
Micturition is basically a spinal reflex which may or may not be influenced by higher centres.
Why do babies wet themselves?
Micturition reflex serves to stimulate parasympathetic contraction and relaxes the external sphincter by inhibiting somatic motoneurones
Higher brain connections have not been established
This is also the case in adult patients with spinal cord transection after the initial period of spinal shock.
What quantitiy of urine in the bladder is enough to initiate the spinal reflex?
300 - 350 mls
Which parts of the brain are involved in delay of voiding?
Descending pathways from many brain centres including the cortex and the brainstem
What is the effect of descending pathways which cause delay?
inhibit the parasympathetic and:
stimulate the somatic nerves to the external sphincter, thus over-ridding the input from the bladder stretch receptors.
What does voluntary inititation involve?
Voluntary initiation involves descending pathways which:
stimulate the parasympathetic and:
inhibit the somatic motor neurones thus summating with the stretch receptor effects.
How are pelvic floor muscles involved in micturition?
Relaxation of pelvic floor muscles can cause sufficient downward tug on the setrusor muscle to initiate its contraction
What parts of the urinary system can be used to prevent urine flow down the urethra/ interrption of urine flow once urination begins
Perineal muscles and external sphincter can be contracted voluntarily, preventing urine flow flowing down the urethra or interrupting the flow once urination begins.
After urination - how does the female and male urethra empty?
Females - by gravity
Males - contractions of the bulbocavernous muscle
What are the abnormalities of micturition?
1.Interruption of afferent nerves
2. interruption of both afferent and efferent nerves
3.interruption of facilitatory and inhibitory descending pathways from the brain.
What is the result of all the abnormalities of micturition?
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.
Paraplegic patients can pinch/stroke their inner thigh to stimulate voiding - the process is called mild mass reflex - what is the mechanism behind mild mass reflex?
Afferent stimuli irradiate from one reflex centre to another
Noxious stimuli may irradiate to autonimc centres and evoke bladder or rectal voiding