Download Renal Physiology 4

Control mechanisms
Renal Physiology 4
1. Renal Blood Flow and GFR
2. Na+ and water
Control of renal function
Class evaluation
Tutorial – test from last term
1. Control of renal blood flow
and GFR
1. Autoregulation
• Autoregulation
a) Myogenic
b) Tubular feedback
2. Sympathetic nervous system
3. Hormonal
a) Angiotensin II
b) Atrial natriuretic peptide
Renal blood flow
Flow
rate
GFR
Arterial blood pressure
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Tubular Feedback
• Autoregulation
1a. Myogenic – same as discussed in
cardiovascular section
•
As flow ↑, stretches arterioles and the smooth
muscles contract, ↑ resistance leads to ↓ flow
• Autoregulation
1b. Tubular feedback
4. Contraction of afferent arteriole- ↓GFR
1. If GFR is High
?
Distal tubule
3. High Na, Cl detected by signal
generated by macula densa
Proximal tubule
? The exact signal in this
autoregulatory system is not knownadenosine and ATP are candidates
2. ↑ NaCl in tubule
Loop of Henle
Collecting duct
2. Sympathetic nervous
system
•
innervates afferent
arteriole
– therefore SNS activity
↓GFR by ↓ blood flow
into glomerular
capillaries
– Circulating epinephrine
also preferentially
constricts afferent
arteriole
2
Angiotensin II
• 3. Hormonal
– Angiotensin II
– Atrial Natriuretic Peptide
renin
Angiotensinogen
Angiotensin
converting
enzyme
Angiotensin I
Angiotensin II
•General vasoconstriction
•Efferent arteriole more sensitive the
afferent arteriole
Low AngII → efferent constriction > afferent
High AngII → both constrict, ↓ Renal blood flow & ↓ GFR
Atrial Naturietic Peptide
Eg. you drink 1 liter of water
↑ Blood volume → ↑ atrial stretch
↑ ANP released from atria
Renal arterioles
1. Afferent dilation
2.Efferent constriction
• Summary for renal Blood Flow and GFR
– Renal blood flow is the main determinant of
GFR
– Autoregulation helps maintain GFR over a
range of arterial blood pressure
– SNS, AngII major regulators of renal blood
flow
– In major crisis (bleeding) renal blood flow can
be shut down to preserve arterial pressure
↑ GFR, without changing blood flow
3
Na+ & Water reabsorption
Since Na+ is the main ion which generates osmotic
forces, regulation of Na and water are directly
linked
Examples,
• if blood volume is low, Na+ reabsorption is
increased to draw water back into the system
– Concentrated urine
• If Na+ concentration is low, extra water is
allowed to be excreted to return Na+ to normal
Main factors controlling Na+ and water
1.
2.
3.
4.
Sympathetic nervous system
Renin-Angiotensin-Aldosterone
Atrial Natriuretic peptide
Anti-diuretic hormone/vasopression
– Dilute urine
Control of Na+ and water
Control of Na+ and water
2. Renin-Angiotensin II-Aldosterone
1. SNS
a) Vasoconstriction of afferent arteriole ↓ GFR,
therefore ↓ filtration
b) ↑ SNS activity → ↑ Renin secretion
Angiotensin
converting
enzyme
renin
Angiotensinogen
Angiotensin I
vasoconstriction
↓ Renal blood
flow & ↓ GFR
Angiotensin II
↑ ADH secretion from
Pituitary
↑ Aldosterone secretion
from adrenal cortex
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Renin-Angiotensin II-Aldosterone
2. Renin-Angiotensin II-Aldosterone
Blood
vessels
esp. Lung
Stimuli for renin secretion
Low Pressure in the
afferent arteriole
↑ SNS
activity
Angiotensin I
Pituitary
Angiotensin II
Low [NaCl] at
macula densa
vasoconstriction
Angiotensin
converting
enzyme
↑ renin
Angiotensinogen
Angiotensin I
ADH
Adrenal Cortex
Angiotensinogen
aldosterone
Angiotensin II
Liver
renin
Kidney
aldosterone
• Angiotensin II is the major factor
controlling Aldosterone secretion from
adrenal cortex
nucleus
• Effects of Aldosterone
– Increase of Na+ channels on apical
membrane of tubular epithelial cells
– Increase ability to reabsorb sodium
Na
Na
Na
K
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3. Atrial Natriuretic Peptide
Stimulus for secretion is atrial stretch (i.e. ↑
blood volume)
1. Dilation of afferent arterioles,
constriction of efferent arterioles
5. Inhibits ADH release
4. Inhibits NaCl
reabsorption by
collecting duct
2. Reduces renin secretion
• Since the stimulus for ANP is high blood
volume/atrial stretch
– The effect of ANP is to increase GFR and
allow more water to be excreted
ANP
3. Inhibits aldosterone
secretion
Direct effect
Indirect effect
4. ADH/vasopressin
ADH is secreted by hypothalamic neurons at the posterior
pituitary
Factors regulating ADH secretion
Osmoreceptors (cells of the hypothalamus)
Normal Physiological Control:
a) Osmoreceptors in the hypothalamus
Respond to osmolarity changes
occurring due to gain or loss of water
Big Changes in Blood Pressure (bleeding)
b) Cardiovascular baroreceptors
Recall changes in water volume redistribute both
intra- and extracellular fluid
Other:
c) Angiotensin II stimulates ADH release
d) ANP inhibits ADH release
6
ADH secretion, osmolarity, and blood
pressure
So what does ADH/vasopressin do?
Aquaporin-3/4
SNARE-dependent
Plasma
[ADH]
H2O
Aquaporin-2 –
H2O channel
270
280 290
Plasma osmolarity
(mOsm)
-20 -10
0
PKA
cAMP
AC
10
% change in blood pressure
vasopressin
Thirst
• AQP-2 channels are constantly cycling to and
from the apical cell surface of collecting duct
epithelial.
• AQP-3/4 normally present on baso-lateral
membrane
• The activity of the ADH/vasopressin receptor
leads to phosphorylation of AQP-2
– Increases rate of exocytosis, reduces the rate of
endocytosis, or both
• Therefore more AQP-2 remains at the cell
surface, increasing H2O permeability
• Thirst center is in the hypothalamus
↓ Plasma volume
↑ Osmolarity
Dry mouth
baroreceptors
osmoreceptors
Angiotensin II
Thirst center
Regulate fluid intake
7
K+ regulation
Summary
Water only moves by osmosis, so regulating
the reabsorption or excretion of Na+ is
the key factor in water volume regulation
– SNS and hormones are major factors by
controlling GFR and permeability
• Normally, almost all filtered K+ is
reabsorbed,
• But K+ can be secreted mainly by the
collecting duct
• Normal intake: 100, normal excretion, 9095
• K+ the major intracellular cation
• Changes in extracellular [K+] have major
impact on nerve and muscle function by
altering resting membrane potential
[ECF]
4 mM Normal
>5mM hyperkalemia
<3.5 mM hypokalemia
K+ distribution
Main factors controlling K+ uptake into cells:
1. Hormonal
a) Insulin
b) Aldosterone
c) Epinephrine
2. [K+] in extracellular fluid
Occurs in collecting duct
All can upregulate Na/K pump ability to move K into cells
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K+ secretion
K+ secretion
ald
Main factors controlling K+ secretion in
collecting duct
1. Aldosterone
2. [K+] in extracellular fluid
Tubular Fluid
nucleus
Na
Na
Na
K
K
K
K channels particularly
abundant in collecting
duct, allowing K to be
secreted in tubular
fluid
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