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Aspects Hémodynamiques et Hypertension Portale
DU Réanimation Hépatique 23 novembre 2012 Dr Dominique THABUT UPMC, AP-HP, Hôpital Pitié-Salpêtrière Paris, France
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Histoire Naturelle de l’HTP Augmentation Pression Porte (GPH > 10 mmHg)
Formation de Varices Rétention hydrosodée
Dilatation des varices Ascite
Rupture de varices (GPH > 12 mmHg)
Mortalité à un an: 1%
Mortalité à un an: 3%
Mortalité à un an: 20%
Mortalité à un an: 50%
Pas de Traitement
Mechanisms of Portal Hypertension
Ø Pressure (P) results from the interaction of resistance (R) and flow (F):
P = R x F
Ø Portal hypertension can result from: Ø increase in resistance to portal flow and/or Ø increase in portal venous inflow
MECHANISMS OF PORTAL HYPERTENSION
SINUSOIDAL PORTAL HYPERTENSION
Cirrhotic liver
Portal vein
Sinusoidal Portal Hypertension Portal systemic collaterals
Splenomegaly
1. Increased hepatic vascular resistance
3. Increased splanchnic blood flow
2. Formation of portosystemic collaterals
éR éP éF
P = R x F
SINUSOIDAL PORTAL HYPERTENSION
Cirrhotic liver
Portal vein
Sinusoidal Portal Hypertension Portal systemic collaterals
Splenomegaly
1. Increased hepatic vascular resistance
3. Increased splanchnic blood flow
2. Formation of portosystemic collaterals
éR éP éF
P = R x F
Augmentation de la résistance vasculaire intrahépatique
2 composantes
1.Composante mécanique Remaniements architecturaux Fibrose Oblitération vaisseaux
2.Composante dynamique Dysfonction endothéliale Augmentation du tonus vasculaire
L’augmentation de la résistance vasculaire intrahépatique: une cible thérapeutique ?
Vasodilatateurs NO
Monoxyde de carbone Prostaglantines
Vasoconstricteurs Endothéline Angiotensine
Norépinéphrine Leucotriènes Thromboxane
…
IN THE NORMAL LIVER, NITRIC OXIDE PLAYS AN IMPORTANT ROLE IN THE REGULATION OF INTRAHEPATIC RESISTANCE
Normally Nitric Oxide (NO) Plays A Major Role in Regulating Intrahepatic Resistance
IN CIRRHOSIS, NITRIC OXIDE ACTIVITY IS REDUCED AND THE ACTIVITY OF VASOCONSTRICTORS IS INCREASED In Cirrhosis, Nitric Oxide (NO) Activity is Reduced and Vasoconstrictors (VC) are Increased
SINUSOIDAL PORTAL HYPERTENSION
Cirrhotic liver
Portal vein
Sinusoidal Portal Hypertension Portal systemic collaterals
Splenomegaly
1. Increased hepatic vascular resistance
3. Increased splanchnic blood flow
2. Formation of portosystemic collaterals
éR éP éF
P = R x F
Formation des collatérales Reperméabilisation vaisseaux pré-existants
Formation des collatérales Reperméabilisation vaisseaux pré-existants
Formation nouveaux vaisseaux (angiogenèse)
Portal hypertension
Porto-systemic shunts
Venous return
NO
eNOS activity
Shear stress
Vasodilatation
Cardiac output
Hyperdynamic Circulation in Cirrhosis: Role of Nitric Oxide (eNOS)
Lebrec and Moreau 2000.
Augmentation du débit sanguin splanchnique
Vasodilatation splanchnique
Syndrome hyperkinétique: Augmentation IC Diminution résistances périphériques Hypovolémie effective Activation du SRA, rétention hydrosodée
SINUSOIDAL PORTAL HYPERTENSION
Cirrhotic liver
Portal vein
Sinusoidal Portal Hypertension Portal systemic collaterals
Splenomegaly
1. Increased hepatic vascular resistance
3. Increased splanchnic blood flow
2. Formation of portosystemic collaterals
éR éP éF
P = R x F
Vasodilation and Hyperdynamic Circulation in Cirrhosis - Multiple Organ Involvement
Splanchnic vasodilation
Peripheral vasodilation
Pulmonary vasodilation
Cerebral vasodilation
Vasodilation and Hyperdynamic Circulation in Cirrhosis - Multiple Organ Involvement
Peripheral vasodilation Decrease effective blood volume
Renal vasoconstriction Hepatorenal syndrome
Na / H2O retention
Ascites
Portal venous inflow Variceal growth
Splanchnic vasodilation
Varices and Variceal Hemorrhage
SINUSOIDAL PORTAL HYPERTENSION
Cirrhotic liver
Portal vein
Sinusoidal Portal Hypertension Portal systemic collaterals
Splenomegaly
1. Increased hepatic vascular resistance
3. Increased portal blood flow
2. Formation of portosystemic collaterals
éR éP éF
P = R x F
Donneurs NO Activateurs NOSe Inhibiteurs endothéline
Somatostatine Terlipressine B-Bloquants Anti-angiogéniques
Somatostatine Terlipressine B-Bloquants Anti-angiogéniques
