regulation of extracellular volume and blood pressure · blood pressure water balance salt balance...
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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