physiology note - cirrhosis.pdf

7/29/2019 Physiology note - cirrhosis.pdf

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Physiology notePathophysiology of cirrhosisIntensive Care Training Program

Radboud University Nijmegen Medical Centre

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Important issues

Volume resuscitation / ascites management

Hepatorenal syndrome

Hepatopulmonary syndrome

Cardiomyopathy and right heart failure

Hepatic encephalopathy

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High cardiac outputLow blood pressure

Low vascular resistance

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Body fluid distribution

Splanchnic blood volume increased (> 20%

of total blood volume)

Central effective blood volume decreased

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Monitoring the effect of

fluid expansion

N = 50 (severe liver cirrhosis - AKI)Umgelter A. BMC Gastroenterol 2008;8:39

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Monitoring the effect of

fluid ex ansion

Umgelter A. BMC Gastroenterol 2008;8:396


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Role of albumin in

cirrhosis

Prevention of paracentesis-induced

circulatory dysfunction

Prevention of renal failure during SBP

Treatment of hepatorenal syndrome in

combination with vasoconstrictors

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Paracentesis induced

circulatory collaps Up to 75% after large volume paracentesis

Caused by rapid reaccumulation of fluid inperitoneal cavity and decrease in SVR due

to an increase in CO

With large volume paracentesis (> 4 - 5 L)

6 - 8 g of albumin per litre of removed fluid

should be given

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Prevention of renal

failure during SBP One-third of these patients develop AKI

Cytokines and circulating vasodilatorsinduce hypovolemia and functional kidney

injury

In those patients developing AKI albumin

1.5 g/kg and on the third day 1 g/kg should

be infused

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Hepatorenal syndrome

Induced by splanchnic vasodilatation and

reduced central arterial blood volume

resulting in extreme renal vasoconstriction

Hepatic failure and ascites

Creatinine > 133 mol/l

No shock, ongoing infection, nephrotoxic agents or fluid loss

No improvement after diuretic withdrawal and fluid resuscitation

Proteinuria < 0.5 g/day and normal renal sonography

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Subtypes of HRS

Type I - within 2 weeks doubling of sCr to

more than 220 mol/l or a 50% decrease in

clearance to less than 20 ml/min - usuallyinpatient with precipitating event - median

survival 2 - 4 weeks

Type II - steady and slowly increasing sCr inoutpatient with ascites - median survival 5 -

6 months

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Treatment

Transjugular intrahepatic portosystemic

shunt (TIPS) and liver transplantation

Vasoconstrictors to reduce splanchnic

vasodilatation - most effective terlipressin

but associated with more cardiovascular

complications and no increase in longtermmortality - combine with albumin

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Hepatopulmonary

s ndrome

Liver disease

Pulmonary vascular dilatation

Defect in oxygenation

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Pulmonary vascular

dilatation Dilatation of pre-capillary and capillary

vessels to 15 - 100 m (normal 7 - 15 m)

Less frequent pleural and A-V

communication and portopulmonary

venous anastomoses

30% impairment in HPV (together with

shunt orthodeoxia and platypnea)

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Intrapulmonary

dilatation

Contrast echocardiography

Pulmonary angiography

Chest CT

Lung perfusion scanning

No effective treatment except transplantation17


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Portopulmonary

hypertension mPAP > 25 mm Hg in rest and > 30 mm Hg

with exercise with PCWP < 15 mm Hg in

the presence of portal hypertension

Overall prevalence 8.5%

No association between severity ESLD and

PHT

Histology identical to primary pulmonary

hypertension

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Important considerations

Therefore PVR > 240

dyn.s.cm-5 important for

diagnosis

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Treatment

Consider for LTx only with adequate res-

ponse to vasodilators

No RCTs for this specific condition

Epoprostenol-treprostinil-iloprost/

bosentan/sildenafil

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Hepatic hydrothorax

2 - 10%, 85% right-sided, transudate

Ascitic fluid > 500 ml in the pleural cavity ina patient with cirrhosis and no other cause

Movement of ascites fluid through small

defects in diaphragm

13% develop spontaneous infection

Liver transplant / TIPS / VATS repair of defects21


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Hepatic encephalopathy

Type A - rapidly progressive associated with

ALF

Type B - chronic periodic or persistent

associated with portosystemic bypass in

the absence of intrinsic liver disease

Type C - idem in the presence of liver

cirrhosis and portal hypertension

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Detry O. World J Gastroenterol 2006;12:7405-7412

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Ammonia-glutamine

hypothesis

Tofteng F. J Cereb Blood Flow Metab 2006;26:21-2725


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Ammonia-glutamine

hypothesis

Tofteng F. J Cereb Blood Flow Metab 2006;26:21-2726


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Lactulose leads to gut acidification with suppression

of ammoniagenic bacteria27


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Brain edema with ALF

Grade I and II - low, Grade III 25 - 35% and

Grade IV 65 - 75%

Usual therapy including hypothermia

Liver transplantation only definitive therapy

but significantly higher morbidity and

mortality if high grade encephalopathy

present

physiology note - cirrhosis.pdf

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