Physiology of Micturition and Assessment of Renal Function Urea Creatinine and GFR Flashcards
Why is it important to be able to assess renal function?
It has a central role in homeostasis
What are 2 clinical situations where ability to measure GFR is particularly useful?
- Patients with renal disease, progression of underlying disease leads to nephron destruction and decreased nephron function
- Total GFR = sum of all filtration by functioning nephrons so progression of disease is indicated by reduction in GFR
- Many drugs (such as digitalis and many antibiotics) are removed by excretion by filtration
- When GRF falls excretion falls so [drug] in plasma may rise causing toxicity, therefore may need to adjust disease appropriate to decrease in renal function
What is the total GFR made from?
Sum of all filtration by functioning nephrons
What can happen when GFR falls in terms of drugs?
[Drug] in plasma may rise causing toxicity, therefore may need to adjust disease appropriate to decrease in renal function
What test is done to measure renal function?
Plasma renal tests
What substance is used to measure rnal function in plasma clearance tests?
Various substances, not just one
In plasma clearance tests, what does clearance relate to?
Volume of plasma cleared not the quantity of subtance removed from plasma
What formula describes plasma clearance?
What is the gold standard for performing and plasma clearance test?
- Insulin clearance, polyfructose, loading IV dose of insulin, allow time to equilibrate, then sample simultaneously plasma and urine (during a timed urine sample)
Why is insulin clearance a good measure of GFR?
Insulin if freely filtered at the glomerulus and neither reabsorbed nor secreted, it is not metabolised by the kidney nor does it interfere with normal renal function so insulin clearance is a measure of GFR:
How does the clearance of substances filtered and resborbed compare to insulin?
Lower clearance, because [UX] will be less than if only filtered and [PX] higher
How does the clearance of substances filtered and secreted compare to insulin?
- a higher clearance than because [UX] will be higher and [PX] lower
In the formula for plasma clearance of x, what is Ux?
Urine concentration of x
In the formula for plasma clearance of x, what is V?
Urine flow rate
In the formula for plasma clearance of x, what is Px?
Plasma concentration of x
What is the normal GFR in ml/min?
125ml/min
Why are GFR values in woman lower than in men?
GFR correlates with surface area, which woman generally have less of in their kidneys
How does GFR change with age?
- GFR declines by about 1ml/min/year after 30
How does the GFR of woman compare with men?
About 10% lower
What is used to clinical practice to measure GFR?
51Cr-EDTA
In clinical practice insulin is no longer used because too cumbersome (large and heavy), 51Cr-EDTA is used instead, is a radioactive substances handled by kidney in the same way as insulin:
- Its now considered that GFR is usually too complex and expensive to measure
- Takes several hours and requires injection of isotope 51Cr EDTA
Why is insulin no longer used in clinical practive to measure GFR?
Too cumbersome (large and heavy)
Is GFR often measured clinically?
No, it is now considered to usually be too complex and expensive to measure
eGFR is measured instead
What is usually used to estimate GFR?
Creatinine clearance
What is creatinine the breakdown product of?
Muscle creatine
What is a big caution when using creatinine as an estimate for GFR?
Is not a linear relationship
What is the estimated GFR form creatinine written as?
eGFR
What are some factors affecting serum creatinine?
- Muscle mass
- Athletes vs malnutrition
- Dietary intake
- Creatine supplements vs vegetarians
- Drugs
- Some lead to spurious increases as does ketoacidosis
Why is using creatinine to measure GFR flawed?
There are some other factors that impact serum creatinine, thats why it is an estimate of GFR
What is the universal expression for normal GFR?
About 100ml/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?
0 because all of it is normally reabsorbed
How does the clearance of urea compare to insulin?
Is less than insulin because some of urea is reabsorbed
What does PAH stand for?
Para-amino-hippuric acid
What is para-amino-hippuric acid (PAH)?
An organic anion
What is used to measure real plasma flow?
Para-amino-hippuric acid (PAH)
What does RPF stand for?
Real plasma flow
Why is PAH used to measure RPF?
- Freely filtered a the glomerulus
- Then remaining PAH in plasma is actively secreted into the tubule
- So that >90% of plasma is cleared of its PAH content in one transit of the kidney
What is the normal renal plasma flow?
660mls/min
How does the clearance of penicillin compare to insulin?
Greater clearance than insulin because filtered and secreted
What is the renal handling of x, when for x filtration is greater than excretion?
What is the renal handling of x, when for x excretion is greater than filtration?
What is the renal handling of x, when for x filtration and excretion are the same?
What is the renal handling of x, when for x clearance is less than insulin clearance?
What is the renal handling of x, when for x clearance is equal to insulin clearance?
What is the renal handling of x, when for x clearance is greater than insulin clearance?
What causes urine to flow from the kidneys to the ureters?
Peristaltic contraction of smooth muscle of ureters
At what angle to the ureters enters the bladder?
Oblique angle
Why do the ureters enter the bladder at an oblique angle?
Prevent reflux of urine
Does the composition of urine change once it leaves the kidney?
No, the bladder only stores it
What is the bladder?
Bladder is a bag of smooth muscle, arranged in spiral, longitudinal and circular bundles:
- These muscles are known as detrusor muscle
- Contraction is mainly responsible for emptying the bladder during micturition
What are the muscles of the bladder known as?
Detrusor muscle
What is contraction of the detrusor muscles responsible for?
Mainly responsible for emptying the bladder during micturition
What sphincters are present in the urinary tract?
Two sphincters:
- Internal urethral “sphincter”
- Is not a true sphincter, but is where smooth muscle at the start of urethra acts as a sphincter when the smooth muscle is relaxed
- External urethral sphincter
- Is a true sphincter, made up of skeletal muscle under voluntary somatic control
Which of the 2 sphincters of the urinary tract is not a true sphincter?
- Internal urethral “sphincter”
- Is not a true sphincter, but is where smooth muscle at the start of urethra acts as a sphincter when the smooth muscle is relaxed
Is the smooth muscle relaxed or contracted when the internal urethral sphincter prevents flow of urine?
Relaxed
Is the external urethral sphincter made up of skeletal or smooth muscle?
Skeletal muscle
Is the internal urethral sphincter made up of skeletal or smooth muscle?
Smooth muscle
What is the bladder overlain with?
Peritoneum
What does the bladder lie posterior and anterior to?
- In midline posterior to pubic bones
- Anterior to reproductive system and rectum
Is the bladder formed from skeletal or smooth muscle?
Smooth muscle (Detrusor muscle)
What classification of epithelium is present in the bladder?
Transitional epithelium
What is the trigone of the bladder?
Smooth triangular region formed by two ureteric orifices and internal urethral orifice
Does urethral obstruction cause bilateral or unilateral renal problems?
Bilateral
Does ureter obstruction cause bilateral or unilateral renal problems?
Unilateral
What is the shape of the pressure-volume curve of the bladder?
Pressure-volume curve of the bladder has a characteristic shape:
- Long flat segment as initial increments of urine enter the bladder
- Then sudden sharp rise as the micturition reflex is triggered
What is the pressure-volume curve of the bladder known as?
Cystometrogram
What is normal daily urine production?
Varies between 750ml-2500ml in temperature climates
How is the bladder controlled in a relaxed state?
Tonic CNS input:
- internal sphincter is pasively contracted
- external sphincter stays contracted
Explain the motor innervation for micturation?
- Rich parasympathetic supply (pelvic nerves)
- Increase in activity causes increase in contraction of detrusor muscle
- This increases pressure in bladder
- From S2-S4
- Sparse sympathetic supply
- Hypogastric nerves
- Inhibit bladder contraction and closes internal urethral “sphincter”
- Sympathetic supply is not very important to bladder function but cutting the hypogastric nerve increases frequency of micturition
- Main function is to prevent reflux of semen into the bladder during ejaculation
- Controlled by nerves L1-L3
- Somatic motoneurons
- Pudendal nerves
What does the parasympathetic supply to the bladder cause?
Increase in contraction of detrusor muscles, increasing pressure in the bladder
From what spinal levels does the parasympathetic supply to the bladder come from?
S2-S4
What are the nerves called that give the sympathetic supply to the bladder?
Hypogastric nerves
What is the action of sympathetic supply on the bladder?
Inhibit bladder contraction and closes internal urethral sphincter
What happens when you cut the hypogastric nerve?
Increases frequency of micturition
What is the main function of the sympathetic supply to the bladder?
L1-L3
What spinal levels controls the sympathetic supply to the bladder?
L1-L3
What are the somatic motoneurons to the bladder called?
Pudendal nerves
What do the somatic motoneurons (pudendal nerves) to the bladder do?
- Innervate skeletal muscle that forms external urethral sphincter, keeping the sphincter closed even against strong bladder contracts
What spinal levels control the somatic motoneurons to the bladder?
S2-S4
How is sensory innervation received from the bladder?
- Stretch receptor afferents from bladder wall, as bladder fills discharge in afferent nerves to spinal cord increases via interneurons, this causes
- Excitation of parasympathetic outflow
- Inhibition of sympathetic outflow
- Inhibition of somatic motoneurons to external sphincter
- Pathways to sensory cortex to create sensation of fullness
What does the discharge in afferent nerves from the bladder to the spinal cord via interneurons cause?
- Excitation of parasympathetic outflow
- Inhibition of sympathetic outflow
- Inhibition of somatic motoneurons to external sphincter
- Pathways to sensory cortex to create sensation of fullness
What can micturition be described as in terms of nervous control?
Spinal reflex that may or may not be influenced by higher centres
What happens to nerves as the bladder becomes filled?
As bladder fills becomes distended and stretch receptors are increasingly stimulated until output becomes great enough to cause bladder contraction via:
- Stimulation of parasympathetic
- And relax the external sphincter by inhibiting the somatic motoneurons
Why do babies pee themselves?
In “leaky” babies the micturition reflex operates at this level because higher brain connections have to be established:
- Also the case in adults with spinal transection after initial period of spinal shock
What is the volume of urine required to inititate the spinal reflex for micturition in adults?
About 300-350mls
How is delay of micturition accomplished?
Delay is accomplished by descending pathways from many brain centres, including cortex and brainstem which:
- Inhibit parasympathetic
- And stimulate somatic nerves to external sphincter thus overriding the input from bladder stretch receptors
What odes voluntary initiation of micturition involve?
Voluntary initiation involves descending pathways which:
- Stimulate parasympathetic and inhibit somatic motor neurons thus summating with the stretch receptor affects
What is one of the initial events in micturition that may be sufficient on its own to intiate contraction of the detrusor muscles?
Relaxation of the pelvic floor muscles which may provide sufficient downward tug on the detrusor muscle to intitate its contraction
What can be contracted voluntarily to prevent urine flow once urination has began?
Parineal muscles and external sphincter
What happens to urine left over in males and females after urination?
Female urethra empties by gravity
Urine in male urethra is expelled by contraction of bulbocavernous muscle
What are abnormalities of micturition usually due to?
Neural lesions
What are the 3 major types of abnormalities 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
What happens in all 3 major types of abnormal micturition due to neural lesions?
- 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
What does paraplegic mean?
Impairment in motor or sensory function of lower limbs
How can paraplegic patients initiate voiding themselves?
Some have trained themselves to initate voiding by pinching or stroking their thights, which is a mild mass reflex
