Regulation of Extracellular Volume and Blood Pressure. Věra Čertíková Chábová Department of Nephrology, 1st Medical Faculty, Charles University

Transcription

1 Regulation of Extracellular Volume and Blood Pressure Věra Čertíková Chábová Department of Nephrology, 1st Medical Faculty, Charles University

2 BP = heart output x resistance Blood pressure Input/output Water balance Salt balance Input/output Osmolality Osmolality = total osmoles/volume

3 Extracellular fluid volume regulation

4 OVLT organum vasculosum laminae terminalis SFO subfornical organ PVN periventricular nucleus SON supraoptic nucleus Osmolality regulation

5 setpoint Short term baroreceptor reflex Long term water /salt output Intermediate term RAS BP regulation

6 afferent arteriole pressure NaCl delivery to macula densa β1 adrenergic receptors Renin AA afferent arteriole EA - efferent arteriole EGM - extraglomerular mezangial cells GC granular cells MD - macula densa N nerve

7 ?? Renin production 1)Decreased 2)Normal 3)Increased

8 ?? Renin production 1)Decreased 2)Normal 3)Increased Renin production 1)Decreased 2)Normal 3)Increased

9 1 Reabsorbed 67% 3 Reabsorbed 5% 33% left 8% left 2 Reabsorbed 25% 3% left 4 Reabsorbed 3% 0,4% left

10 Osmotic diuretics acetazolamide Cl - Hydrochlorothiazide H + Aldosterone amiloride K + 2 Cl - Furosemide

11 ECV ECV BP = urine Pressure natriuresis

12 Lumen PROXIMAL TUBULE Intersticial space BP 20-HETE Angiotensin II 3 2 K + ATP H + Pressure natriuresis

13 renal sympathetic acivity renal ang II plasma ang II renal prostaglandins relaxation contraction Autoregulation

14 ? GF = 90 ml/min Filtered load 12.6 mmol/min GF = 120 ml/min Filtered load 16.8 mmol/min end of proximal tubule 1) 4,2 mmol/min 2) 5,6 mmol/min 4,2 mmol/min 3) 8,4 mmol/min?

15 GFR Prox. tubule 35% filtered Glomerulotubular balance

16 Lumen PROXIMAL TUBULE Starling forces Krev from glomerulus norm. FF Intersticial space Blood 1 Active transport 2 P PC = 20 Passive backleak 3a 3b π PC = 33

17 Lumen PROXIMAL TUBULE Starling forces Krev From glomerulus FF Intersticiální prostor Blood 1 Acctive transport 2 P PC = 17 Passive backleak 3a 3b π PC = 40

18 SMC Tubuloglomerular feedback contraction Ca + ATP adenosin 2 Cl - K + AA GC renin MD contraction MC

19 renal arterial pressure glomerular pressure renal blood flow GFR rate of flow through macula densa Vasoconstrictive signal Afferent arteriolar constriction Tubuloglomerular feedback

20 Lumen - PRINCIPAL CELL OF THE CONNECTING TUBULE Interstitial space Renin ANG II plasma K + K + K + ACTH Aldosterone ENAC 3 2 K + ATP Aldosterone effect

21 Lumen - PRINCIPAL CELL OF THE CONNECTING TUBULE Aldosteron e proteins mrna MR MR nucleus ENAC ATP 3 2 K + ATP Intersticial space Aldosterone effect

22 BP renal ang II Hypertension afferent arteriolar pressure glomerular capillary pressure peritubular capillary pressure GFR renal interstitial pressure proximal tubule fluid/salt reabsorption diuresis/natriuresis ECF BP

23 Hypertension Renin ACE polymorphisms 3 2 K + ATP α-adducin polymorphism AT 1 receptor aldosterone Cl - Gordon s syndrome glucocorticoid remediable aldosteronism activated mineralocorticoid receptor Apparent mineralocorticoid excess 11β-hydroxylase deficiency Liddle s syndrome SGK activation SGK serum and glucocorticoid-regulated kinase

24 ADH SNS RAS endothelin ANF Hemodynamic changes Impaired autoregulation Salt & water retention Congestive heart failure

25 Portal hypertension Liver cirrhosis NO Splanchnic + periferal vasodilation lymph production Efective circulating volume cadiac output ADH SNS RAS & H 2 0 retention Renal vasoconstriction ascites renal blood flow

26 Nephrotic syndrome α β γ α β γ α β γ plasmin * * * ENaC * inhibitory peptide

27 Nephrotic syndrome Urokinase Plazminogen Plazmin * * * ENaC * inhibitory peptide

28 On the basis of preceding two slides, the diuretic regimen of a patient with nephrotic syndrome should include: 1)Furosemide 2)Hydrochlorothiazide 3)Amiloride??

29 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.

30 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.

31 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,