Regulation of Extracellular Volume and Blood Pressure
Transcript of Regulation of Extracellular Volume and Blood Pressure
Regulation of Extracellular Volume
and Blood PressureVěra Čertíková Chábová
Department of Nephrology, 1st Medical Faculty, Charles University
Blood pressureWater balance
Salt balance
BP = heart output x resistance
OsmolalityOsmolality = total osmoles/volume
Input/output
Input/output
Extracellular fluid volume regulation
OVLT – organum vasculosum laminae terminalisSFO – subfornical organPVN – periventricular nucleusSON – supraoptic nucleus
Osmolality regulation
Short term
Intermediate term
setpoint
Long term
BP regulation
baroreceptor reflex
RAS
water /salt output
AA – afferent arteriole EA - efferent arterioleEGM - extraglomerular mezangial cells GC – granular cells MD - macula densa N – nerve
β1 – adrenergic receptors
afferent arteriole pressure NaCl delivery to macula densa
Renin
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Renin production1)Decreased2)Normal3)Increased
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Renin production1)Decreased2)Normal3)Increased
Renin production1)Decreased2)Normal3)Increased
0,4% left
3% left8% left
33% left
Reabsorbed25%
2
Reabsorbed67%
1
Reabsorbed3%
4
Reabsorbed5%
3
Na+
Na+
Na+H+
2 Cl-
Na+
K+
Na+
Cl-
Na+
Osmotic diureticsacetazolamide
Furosemide
Hydrochlorothiazide
Aldosteroneamiloride
Pressure natriuresis
BP
ECV
urine Na+
ECV
=
Na+
Na+
Na+
Na+
Na+
Lumen Intersticialspace
ATP
3 Na+
2 K+
PROXIMAL TUBULE
Na+
H+
Pressure natriuresis
BP
Angiotensin II20-HETE
Autoregulation
↑ renal ang II ↑ plasma ang II↑ renal sympathetic acivity
↑ renal prostaglandins
contraction
relaxation
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Na+ end of proximal tubule
1) 4,2 mmol/min
2) 5,6 mmol/min
3) 8,4 mmol/min
GF = 90 ml/minFiltered Na+ load 12.6 mmol/min
Na+ 4,2 mmol/min
GF = 120 ml/minFiltered Na+ load 16.8 mmol/min
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Glomerulotubular balance
Prox
. tub
ule
GFR
35% filtered Na+
Krev
Intersticialspace
Starling forcesPROXIMAL TUBULE
from glomerulusnorm. FF
Active transport
Passive backleak
PPC = 20
πPC = 33
Lumen
Blood
1
2
3a 3b
Krev
Intersticiálníprostor
PROXIMAL TUBULE
From glomerulus↑FF
Acctive transport
Passive backleak
PPC = 17
πPC = 40
Lumen
Blood
1
2
3a 3b
Starling forces
2 Cl-
Na+K+
MDAA
Ca+
MC
GC
SMC Tubuloglomerular feedback
ATPadenosin
contraction
contraction
renin
↑ renal arterial pressure
↑ rate of flow through macula densa
↑GFR
↑renal blood flow↑ glomerular pressure
Vasoconstrictive signal
Afferent arteriolar constrictionTubuloglomerular feedback
Lumen Interstitialspace-
ATP
3 Na+
2 K+
K+K+
PRINCIPAL CELL OF THE CONNECTING TUBULE
Na+
ENAC
Aldosterone
Aldosterone effect
Renin – ANG II
ACTH
↑plasma K+
Lumen-
ATP
3 Na+
2 K+Na+
ENAC
Aldosterone
ATP
mRNAMR
MR
proteins
Intersticialspace
nucleus
Aldosterone effect
PRINCIPAL CELL OF THE CONNECTING TUBULE
↑ BP↑ afferent arteriolar pressure
↑glomerular capillary pressure
↑ peritubular capillary pressure
↑renal interstitial pressure↑GFR
↓ proximal tubule fluid/salt reabsorption
↑ diuresis/natriuresis
↓ renal ang II
↓ ECF ↓ BP
Hypertension
HypertensionRenin
ACE
AT1 receptor
polymorphisms
aldosterone
activated mineralocorticoid receptor
glucocorticoid remediable aldosteronism
Apparent mineralocorticoid excess11β-hydroxylase deficiency
Na+
Liddle´s syndromeSGK activation
Na+
Cl-
Gordon´s syndrome
ATP
3 Na+
2 K+
α-adducin polymorphism
SGK – serum and glucocorticoid-regulated kinase
Congestive heart failure
Hemodynamic changes
Impaired autoregulation
↑ ADH ↑ SNS ↑ RAS ↑ endothelin ↑ ANF
Salt & water retention
Liver cirrhosisPortal hypertension
Splanchnic + periferal vasodilationNO
↓ Efective circulating volume↑ lymph production
↓ cadiac output
Renal vasoconstriction
↓ renal blood flow
Na+ & H20 retention
ascites
↑ ADH ↑ SNS ↑ RAS
Nephrotic syndrome
α γβ
Na+
α γβ
Na+
*α γβ
Na+
*
plasmin
*
* inhibitory peptideENaC
*
Nephrotic syndrome
ENaC
**
Urokinase
PlazminogenPlazmin
Na+ Na+
* inhibitory peptide
On the basis of preceding two slides, the diuretic regimen of a patient with nephrotic syndrome should include:
1)Furosemide
2)Hydrochlorothiazide
3)Amiloride
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� Sodium and water excretion are controlled by multiple overlaping mechanisms. Most of them are related to blood pressure.� The kidneys have their own mechanisms of
regulating sodium excretion. Key among these are pressure natiuresis and RAS.� The kidneys are the ultimate determinant of
blood pressure in the long term via their control of ECF.
� All the physiological controls in the proximal nephron affect the excretion of sodium and water together.� Aldosterone and AVP in the distal nephron
regulate sodium and water independently. � Long term regulation of sodium excretion
(and blood pressure) centres on the actions of aldosterone.
The figures were adapted from:
Boron & Boulpaep: Medical Physiology, 2nd edition, 2009, Saunders
Eaton DC, Pooler JP: Vander´s Renal Physiology, 6th edition, 2004, McGraw-Hill
Servier Medical Art, www.servier.com