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