Post on 30-Apr-2020
Portal HypertensionJohn F. Reinus, M.D.
The screen versions of these slides have full details of copyright and acknowledgements 1
Portal Hypertension
John F. Reinus, M.D.Chief of Clinical Hepatology
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Chief of Clinical HepatologyMontefiore Medical Center
Professor of Clinical MedicineThe Albert Einstein College of Medicine
Thesis
• Portal hypertension causes multiple regional circulatory derangements that result in extra- and intra-vascular volume overload
d d f ti
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and organ dysfunction
• Vascular smooth muscle tension locally controlled by chemical mediators, autonomic innervation
Regional circulatory regulation
A t i
Cerebral cortex
Mechanoreceptors
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Autonomicinput
Osmoreceptors
Chemoreceptors
Thermoreceptors
Endothelialrelease
NO
COProstacyclin
Endothelin
Portal HypertensionJohn F. Reinus, M.D.
The screen versions of these slides have full details of copyright and acknowledgements 2
• The liver is a metabolically active filter
Normal liver function
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When the liver is sick
Ac te hepatitis
Metabolicdysfunction
X
Portalhypertension
O
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Acute hepatitis
Chronic hepatitis
Liver failure
X
O
X
O
X
X
Normal liver
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Portal HypertensionJohn F. Reinus, M.D.
The screen versions of these slides have full details of copyright and acknowledgements 3
Cirrhotic liver
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Portal pressure
P = Q x R
P ≡ Pressure
P = Q x R
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P ≡ Pressure
Q ≡ Blood flow
R ≡ Resistance
• Flow is determined by venous return from splanchnic organs
• Not effectively limited by changes in portal venous pressure
Portal pressure (2)
P = Q x R
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• Resistance (R) is proportional to 1/r4
(where r is the vascular radius)
• Normal portal vessels are highly compliant because of shear-induced eNOS upregulation
Portal HypertensionJohn F. Reinus, M.D.
The screen versions of these slides have full details of copyright and acknowledgements 4
Cirrhosis and portal pressure
P ∝Q/r4
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• Decreased vascular radius (r)
• Decreased vascular compliance
Increasedportal
pressure
Q/
• Reflex SMA vasoconstriction causes intestinal hypoxia, VEGF and eNOS upregulation
P i h i d i
Initial circulatory effects of portal hypertension
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• Portosystemic shunting causes endotoxemia, iNOS upregulation
Effects of portal hypertension on regional circulations: gut and kidney
VasodilationPortal
hypertension
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Increased intra-vascularvolume and flow
Renal salt and waterretention
Decreased “effective”plasma volume
Portal HypertensionJohn F. Reinus, M.D.
The screen versions of these slides have full details of copyright and acknowledgements 5
Ve ≡ Vp/C
a (normal)
Effective plasma volume
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Vea >Veb
b (portal hypertension)
Effects on renal circulation
Renin
Blood pressure
Epinephrine secretion
Water retentionADH secretion
Sympatheticstimulation
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(kidney)
Angiotensinogen(liver) Angiotensin I Angiotensin II
ACE(lungs) Aldosterone secretion
Vasoconstriction
Na+ retention
The arteriolar vasodilation hypothesis of volume expansion in cirrhosis
VasodilationPortal
hypertension
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Increased intra-vascularvolume and flow
Renal salt and water retention
Decreased “Effective”Plasma Volume
Portal HypertensionJohn F. Reinus, M.D.
The screen versions of these slides have full details of copyright and acknowledgements 6
Cirrhosis and portal pressure
P ∝Q/r4
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• Decreased vascular radius (r)
• Decreased vascular compliance
• Increased portal blood flow
Increasedportal
pressure
The cardiac output at rest in Laennec’s cirrhosisHenry J Kowalski and Walter H. Abelmann, J Clin Invest 1953; 32: 1025-1033
DiagnosisSubjects
(n)Mean CI
(L/min x m2)Mean PVR*
(dynes x sec x cm-5)
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* Normal ranges: CI = 2.6-4.2 L/min x m2; PVR = 900-1200 dynes x sec x cm-5
Fatty Liver
Cirrhosis only
Cirrhosis + ascites
3
11
8
4.76
4.27
5.34
1047
1077
752
The cardiac output at rest in Laennec’s cirrhosis (2)Henry J Kowalski and Walter H. Abelmann, J Clin Invest 1953; 32: 1025-1033
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“The hyperdynamic circulation”
• Increased cardiac output
• Decreased arterial pressure
Portal HypertensionJohn F. Reinus, M.D.
The screen versions of these slides have full details of copyright and acknowledgements 7
Shunting of portal blood flow
Esophagus
LiverCoronary v.
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Spleen
Splenic vein
Kidney
Left renal veinInferior vena cava
Superior mesenteric
vein
Inferior mesenteric
vein
Portal vein
Esophageal varices
• Varices develop in 8% of cirrhotics per year (HPVG > 10mm Hg)
• Bleeding in 5-15% of patients with varices per year
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with varices per year
CPT class E. varices G. varices
A 40% ?C 85% ?
A-C 50% 5-33%
Ascites (liver sweat)
• SOB
• Pain
• Infection (SBP)
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Infection (SBP)
• Umbilical hernia
• Flood syndrome
Portal HypertensionJohn F. Reinus, M.D.
The screen versions of these slides have full details of copyright and acknowledgements 8
Vp/CNormal
P l
Renal function and decreasedeffective plasma volume (v/c)
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Renal function
Oliguria
PrerenalAzotemia
Diuresis
Mortality after decompensation
• Variceal bleeding: 20% six-week mortality
• Ascites: 50% two-year mortality
• SBP: 30% in-hospital mortality
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• HRS-I: 80% two-week mortality
Hepatic vein
TIPS procedure
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Portal vein
Portal HypertensionJohn F. Reinus, M.D.
The screen versions of these slides have full details of copyright and acknowledgements 9
Shunting of portal blood flow
ShuntCoronary v.
Esophagus
Liver
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Portal veinSuperior
mesenteric vein
Inferiormesenteric
veinInferior vena cava
Left renal vein
Kidney
Splenic vein
Spleen
MELD score as a predictor of early death in patients undergoing elective TIPS procedures
Montgomery A, Ferral H, Vasan R, Postoak DW
Cardiovasc Intervent Radiol 2005; 28: 307-312
MELD = 10 {0.957 Ln(Cr) + 0.378 Ln(Bilirubin) + 1.12 Ln(INR) + 0.643}
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MELD as a predictor of 30-day mortality after elective TIPS in 119 patients (death rate = 10.9%)
MELD score TIPS survivors Early mortality1-10 (n=27) 26 1 (4%)11-17 (n=63) 58 5 (8%)18-24 (n=24) 20 4 (17%)>24 (n=5) 2 3 (60%)
Patient Pre-TIPS MELD Cause of death Survival (days)1 13 Sepsis 5
Table 2: Causes of death
MELD score as a predictor of early death in patients undergoing elective TIPS procedures (2)
Montgomery A, Ferral H, Vasan R, Postoak DW,
Cardiovasc Intervent Radiol 2005; 28: 307-312
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p2 29 Multiorgan failure 53 17 Liver failure 74 22 Unknown 275 24 Liver failure 106 11 Unknown 247 34 Multiorgan failure 28 13 Liver failure 169 8 Liver failure 11
Portal HypertensionJohn F. Reinus, M.D.
The screen versions of these slides have full details of copyright and acknowledgements 10
Cardiac hemodynamics in alcoholic patients with chronic liver disease and a presystolic gallop
Gould L, Shariff M, Zahir M, Di Lieto M, J Clin Invest 1969; 48: 860-868
• 10 male cirrhotic patients, ages 41-58 years
• Cardiac catheterization to measure pressures
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to measure pressures, cardiac output at rest and with exercise
• MPAPs, LVEDPs rose while stroke index remained the same or fell
• Conclude that heart demonstratesblunted response to stress
Cirrhotic cardiomyopathy
• Contractile, electrophysiological, chamber-structure abnormalities
Cli i l i t i ti l
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• Clinical signs, symptoms require stimulus
• May contribute to HRS, complications post-TIPS and OLT
gAMP InhibitionCholinergicreceptor Gi protein+
PVR = X 80MPAP - PAOP
CO
PVR ≡ Pulmonary vascular resistance (<240 dynes x sec x cm-5)
MPAP Mean pulmonary artery pressure (15mm Hg)
Pulmonary hypertension
218 = X 8038 - 14
8.8218 = X 80
38 - 148.8
218 = X 8038 - 14
8.8
Volume overload
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MPAP ≡ Mean pulmonary artery pressure (15mm Hg)
PAOP ≡ Pulmonary artery occlusion pressure (8-10mm Hg)
CO ≡ Cardiac output (5-8 L/min)
MPAPMild hypertension
25-35mm hgModerate hypertension
35-50mm hgSevere hypertension
>50mm hg
Portal HypertensionJohn F. Reinus, M.D.
The screen versions of these slides have full details of copyright and acknowledgements 11
Portopulmonary hypertension
• Elevated mean pulmonary artery pressure secondary to increased pulmonary vascular resistance in patients with portal hypertension with or without liver disease
MPAP 25 H t t
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– MPAP > 25mm Hg at rest
– PVR > 240 dynes x sec x cm-5
– Absence of significant volume overload
Portopulmonary hypertension (2)
• Intimal hyperplasia
• Smooth muscle hypertrophy
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• Thrombosis
• Plexiform lesions
Portopulmonary hypertension (3)
• 0.25-4.0% of patients with cirrhosis
• 16.1% of patients with refractory ascites
• Severity of portal hypertension does not correlate with severity of pulmonary hypertension
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with severity of pulmonary hypertension
• Caused by imbalance of mediators favoring constriction, leading to endothelial injury (endothelial dysfunction)
• Doppler echocardiography detects moderate to severe disease with 97% sensitivity, 77% specificity
Portal HypertensionJohn F. Reinus, M.D.
The screen versions of these slides have full details of copyright and acknowledgements 12
Hepatopulmonary syndrome
• Widened age-corrected alveolar-arteriolar O2 gradient on room air in patients with liver disease with or without portal hypertension
– 50-70% of patients with chronic liver disease
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complain of shortness of breath
– 50% of OLT candidates have HPS
– 15-30% of HPS patients have hypoxemia
– No connection with severity of liver disease
Hepatopulmonary syndrome (2)
NO
ET-1(liver)
eNOSupregulation
ETR-B(lung)
Macrophage iNOS (lung)
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Angiogenesis
Dilation of pre-capillary arterioles
CO
( g)
Macrophage HO-1 (lung)
Macrophages(lung)
VEGF-AAngiotensin II
Initiation by shear forces and changes
in blood pressure
Hepatopulmonary syndrome (3)
• 60% of cirrhotics have HPS by saline-contrast TTE
• SpO2 ≤ 95% reliably detects patients with HPS and PaO2< 70mm Hg, 100% sensitivity, 88% specificity
I t ft li t l t i > 85%
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• Improvement after liver transplant in > 85%
PaO2
Mild HPS≥ 80mm Hg
Moderate HPS≥ 60 < 80mm Hg
Severe HPS< 60mm Hg
Portal HypertensionJohn F. Reinus, M.D.
The screen versions of these slides have full details of copyright and acknowledgements 13
Consequences of portal hypertension
Vasodilation
Renal salt, t t ti
Secondarypulmonary
hypertension
Ascites
Cardiomyopathy
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Hyperdynamiccirculation
water retention
Renal failure
Portopulmonaryhypertension
Varices
Hepatopulmonarysyndrome
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Portal Hypertension
John F. Reinus, M.D.
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Chief of Clinical HepatologyMontefiore Medical Center
Professor of Clinical Medicine The Albert Einstein College of Medicine
Portal HypertensionJohn F. Reinus, M.D.
The screen versions of these slides have full details of copyright and acknowledgements 14
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