REB 20. Control of Renal Circulation, Glomerular Filtration Flashcards
What is the filtration rate in the glomerulus dependent on?
Glomerular Blood Flow
Is there any extrinsic regulation to control the renal circulation?
No - only autoregulation (self-regulation)
How does autoregulation of the renal circulation work? What are the basic mechanisms involved?
within NORMAL blood pressure ranges, there are variations in AFFERENT ARTERIOLAR RESISTANCE to ensure CONSTANT blood flow
What is the main goal of autoregulation of the renal circulation?
to ensure CONSTANT blood supply to the afferent arterioles and glomerular capillaries
What is autoregulation (definition)?
It is the term for LOCAL ARTERIOLAR MECHANISMS that keep blood flow CONSTANT despite wider variations in mean arterial (systemic) blood pressure
Different tissues have different autoregulatory abilities. How is the autoregulatory abilities in:
Brain?
Kidney?
Skeletal Muscle?
Brain - excellent
Kidney - good
Skeletal Muscle - poor
What range of blood pressures does autoregulation of the renal circulation occur at?
Mean Arterial Pressure: 80 to 180 mmHg
- this is the autoregulatory range
- it does not occur outside of this range
What is the autoregulatory range?
Mean Arterial Pressure: 80 to 180 mmHg
List the 2 mechanisms of the autoregulation.
[1] Myogenic Response
[2] Tubuloglomerular Feedback
Explain the general overview the myogenic response.
- “muscle-produced”
- increase in pressure in afferent arteriole
- stretch in the wall of the vessel
- causes reflex contraction of its smooth muscle
- increases resistance of the vessel
What are the steps involved in myogenic response to increased pressure?
[1] increased arterial pressure
[2] pressure in afferent arteriole increases
[3] stretch of afferent arteriolar wall
[4] reflex contraction of muscle in wall of afferent arteriole
[5] afferent arteriole resistance increases
[6] renal blood flow kept constant
How does the stretch of the wall of the afferent arteriole cause reflex contraction?
[1] stretch of afferent arteriolar wall
[2] activates stretch-activated non-selective cation channels in smooth muscle
[3] depolarizes cell, Ca2+ influx
[4] muscle contraction
What is the Macula Densa? Where are the Macula Densa cells located?
- region of specialized epithelial cells at point where the thick ascending limb loop of Henle meets distal convoluted tubule
- at the junction of the ascending limb of the loop of Henle and the distal convoluted tubule
Explain the general overview the tubuloglomerular feedback response.
- change in (a) renal blood flow and (b) glomerular filtration rate leads to the change in rate of fluid flow through the tubules
- a signal from the macula densa cells causes a change in the afferent arteriolar tone
What are the steps involved in the tubuloglomerular feedback response to increased pressure?
[1] pressure in the afferent arteriole increases
[2] the glomerular filtration rate increases
[3] the tubular flow rate increases
[4] increased delivery of Na+/Cl- to macula densa
[5] increased NaCl reabsorption by macula densa cells
[6] Na/Cl uptake activates a non-selective cation channel which gates calcium entry that causes macula densa cells to release a PARACRINE AGENT (such as adenosine or ATP)
[7] Adenosine diffuses to afferent arteriole
[8] Afferent ateriolar constriction (renin release is also reduced)
[9] (a) Renal Blood Flow and (b) Glomerular Flow Rate returns to normal
If the tubular flow/salt content is LOW, what happens in the tubuloglomerular feedback response?
Other mediators (PGE2 and NP) are released which stimulate renin and vasodilation
What is the reason for maintaining RBF constant within the MAP range of 80 to 180 mmHg?
- glomerular filtration rate (GFR) is dependent on the glomerular blood flow (GBF)
- the glomerular blood flow (GBF) is dependent on the renal blood flow (RBF)
- therefore, by maintaining RBF you are keeping GFR constant
What are the advantages of autoregulating GFR and RBF over the range of 80 to 180 mmHg? [2]
[1] ensures that small fluctuations in blood pressure which normally occur do not result in corresponding fluctuations in RBF (renal blood flow) and GFR (glomerular filtration rate) [!!]
— e.g. changes in posture, light to moderate exercise
[2] protects fragile glomerular capillaries against increases in perfusion pressure
Does the RBF (renal blood flow) and GFR (glomerular filtration rate) ever change?
They do change under certain conditions - brought about by extrinsic control mechanisms mediated by NERVES and HORMONES
What are the 2 categories of extrinsic control that may lead to changes in the RBF and GFR?
[1] Nervous Control
[2] Hormonal Control
Explain the role of the nervous extrinsic control in the control of RBF and GFR.
[1] afferent and efferent arterioles richly innervated by SYMPATHETIC fibres
[2] there is increased sympathetic nervous system activity
[3] NA causes contraction of the smooth muscle in vessel walls
[4] afferent + efferent arteriole vasoconstriction causes a reduction in RBF and GFR
Explain the role of the hormonal extrinsic control in the control of RBF and GFR.
[1] vascular smooth muscle in the walls of interlobular arteries and afferent + efferent arterioles is sensitive to certain circulating compounds
[2] sensitive to (a) Adrenaline and (b) Angiotensin 2
[3] leads to vascular smooth muscle contraction
[4] leads to vessel constriction
What is the function of the bradykinin?
it leads to the dilation of blood vessels
Explain the role of nerves and hormones (extrinsic control) in:
a person at rest with normal circulating blood volume
[1] activity in sympathetic nervous system fibres supplying the renal vessels is ZERO
[2] RBF and GFR maintained CONSTANT by auto-regulation
Explain the role of nerves and hormones (extrinsic control) in:
severe exercise, pain, severe emotional stimuli on RBF and GFR
[1] sympathetic nervous system activity in renal vessels
[2] adrenaline released from adrenal medulla
[3] vascular smooth muscle contraction
[4] vessel constriction
[5] GFR decreases
Explain the role of nerves and hormones (extrinsic control) in:
effect of crisis situation (e.g. haemorrhage) on RBF and GFR
[1] high degree of sympathetic nervous system activity may be detected in renal vessels
[2] also, adrenaline is released and circulating levels of angiotensin 2 increase
[3] vessel constriction
[4] GFR decreases
What is the benefit of reducing RBF (renal blood flow) during severe exercise?
- helps direct more blood to muscles
What is the benefit of reducing RBF (renal blood flow) during haemorrhage?
- reduced urine production
- helps combat fluid loss
Could a decrease in Renal Blood Flow (RBF) after haemorrhage result in renal ischaemia?
- a severe decrease in RBF can lead to TUBULAR NECROSIS and RENAL FAILURE, but…
- Prostaglandins (PGE2 and PGI2) dampen the vasoconstrictior effects on the afferent arterioles of sympathetic nervous system and angiotensin 2
- are produced WITHIN the kidneys; synthesis stimulated by ischaemia, sympathetic nervous system and angiotensin 2
- balance between PG activity and that of SNS and angiotensin 2 will determine the extent of decrease in RBF
What is the major driving force for glomerular filtration?
- glomerular capillary blood pressure
- large diameter of afferent vs. efferent arteriole generates pressure pushing out plasma through (leaky) capillaries
What passes through the filtration barrier to form the tubular filtrate?
- ALL components of plasma, except cells and proteins, pass through the barrier
Passage through the barrier is influenced by…
- molecular size
- charge (negatively charged molecules are restricted by barrier)
- molecule shape - deformable molecules pass better than rigid ones
What are the 3 factors that influence the passage through the tubular filtrate?
[1] Molecular Size
[2] Charge
- negatively charged molecules are restricted by barrier
[3] Molecule Shape
- deformable molecules pass better than rigid ones
What is the normal Glomerular Filtration Rate (GFR) in males and females? (numerical values)
Males: GFR = 125 mL/min
Females: GFR = 115 mL/min
GFR is normally constant but would decrease in what condition?
renal disease
What does the Glomerular Capillary Blood Pressure have an effect on?
favours filtration
What does the Plasma-Colloid Osmotic Pressure have an effect on?
opposes filtration
What does the Bowman’s Capsule Hydrostatic Pressure have an effect on?
opposes filtration
What does the Net Filtration Pressure have an effect on?
favours filtration
What are 3 layers of the Glomerular Filtration Barrier?
[1] Endothelium of Glomerular Capillaries (very capillaries)
[2] Basement Membrane
- colalgen, glycoproteins
- provide structure and barrier to small proteins
[3] Epithelial Cells of Bownmans Capsulse
What are some of the conditions that will change the GFR?
[1] Alterations in any of the Forces Underlying GFR affect GFR
[2] Physiological Mechanisms Regulating GFR (both act at level or arteriole calibre/resistance)
- – autoregulation (inherent response to stretch of smooth muscle
- – extrinsic sympathetic control (e.g. during haemorrhage)
[3] Other (Unregulated) Influence son GFR
- – decrease in plasma protein reduces force opposing filtration so this increases GFR
- – urinary tract blockage - increase pressure in Bowman’s capsule (decreases GFR
- – plasma-colloid pressure increases in dehydrating diarrhoea so GFR is decreased
How many litres of filtrate is formed per day?
180 L
How many litres of urine (filtrate) is excreted?
1.5 L
How much filtrate is reabsorbed per day?
178.5 L
