Metabolic diversity within zones Relatively poor in O2 and nutrients Rich in oxygen and the nutrients Lipolysis Bile salt formation Glycolysis Glycogen snthesis as well as gluconeogenesis Anaerobic/phaseI reaction Oxidative/phaseII reaction More prone for hypoxic & drug induced damage Less prone to hypoxia and drug toxicity Zone 3(pericentral) Zone 1(periportal)
Effect of induction agents on hepatic blood flow
Rapid sequence induction more likely to cause hypotension
than conventional induction.
Slow titrated dose of induction agents cause less hypotension
All iv induction agents (single dose) can be safely given in pt
with liver dysfunction.
Ketamine cause decrease in HBF thru sympathetic stimulation
whereas other thru dose related decrease in C.O & B.P.
Etomidate – least decrease
Thiopentone sodium – moderate decrease
Propofol - maximum decrease ( 17 % )
Effect of hepatic dysfunction on the drug pharmacokinetics Decreased biliary excretion of drugs Obstructive jaundice Metabolism either can be increased or decreased Enzyme content Increased VOD Ascites Increased unbound fraction Hypoalbuminemia First pass metabolism for the oral drug decreased Decreased PBF & fraction of shunt increased Effect on the drug Liver dysfunction
Effect of hepatic dysfunction on drug pharmacodynamics
Aminotransferace(ALT &AST) Zone 3>1 Zone 1>3 Half life is 36hrs Half life is 18hrs N.Value 0 – 35IU/L N.value O – 45 IU/L Cytosol and mitochondria Cytosol Non specific Relatively liver specific Aspartate transaminase Alanine transaminase
In choledocholithisis caused by CBD stone, the bilirubin value rarely
exceeds 10mg/dl.Sepsis or renal failure should be excluded if the bn
exceeds 30mg/dl in patient with CBD stone.
In cholestatic jaundice due to malignancy, the bilirubin value is >10mg but
but less than 30mg/dl.
Common bile duct obstruction if persist for more than 30 days will result in
liver damage and can lead to the development of cirrhosis.
Serum bilirubin will take atleast 1-2 weeks to return to normal following
the relief of obstruction ( half life of delta bn is 2weeks).
Antibodies in liver disease Chronic hep C & Type 11 autoimmune hepatitis Anti LKM 1 Chronic hepatitis D Anti LKM3 Drug induced chr hepatitis Anti LKM2 Type 1 A.I. Hepatitis Antinuclear antibody Prm sclerosing cholangitis P - ANCA Primary biliarycirrhosis Antimitochondrial AB
Ascites increases the risk of aspiration by increasing intra-
abdominal pressure ( also decreased GITmotility & GERD
due to hiatal hernia in the cirrhotics).
PICD can be prevented by concurrent administration of salt
poor albumin or other colloid.
Ascites is said to be refractory if there is no response to the
maximum dose of furosemide and spiranolactone.
TIPS should be considered for patient with refractory ascites
who is listed for OLT.
Tense and refractory ascites should be drained adequately
before surgery ( significant intra and postop comp.).
Anaesthetic consideration regarding ascites
Ascites Anaesthetic consideration Risk for aspiration False high CVP Haemodynamic instability Splinting effect to diaphragm Increased volume of distribution Intraoperative Respiratory distress Hypotension if inadeq replaced after LVP Hepatic hydrothorax Risk for SBP (50% mortality) Preoperative
V.Cholestatic jaundice Absent Present Cirrhosis stigmata Present Absent H/O of surgery Absent Present Prodromal symptom Present Absent Abdominal pain Present Absent Fever Extrahepatic Intrahepatic Diff. Features
Cholestatic jaundice Present Absent Palpable gallbladder Responsive Variable Vit K treatment Needed Not needed ERCP Present Absent B.Dilatation on USG <30mg/dl Variable Total bilirubin Extrahepatic Intrahepatic Diff. Features
Benign vs Malignant surgical jaundice 10-30mg/dl <10mg/dl Total bilirubin Present Absent Palpable gallbladder Absent Present Abdominal pain Absent Present Fever with chills Insidious Acute Mode of onset Malignant Benign Diff.Features
Anaesthetic consideration in obstructive jaundice
Altered drug handling due to cholestasis
Impaired wound healing.
Measures taken to to reduce the renal failure is responsive better in benign rather than malign condition.In malignancy only way to reduce the
incidence of renal failure is to maintain adequate iv volume and
Effect of obstructive jaundice on the cardivascular system
Negative inotropic effect by bile salt.
Negative chronotropic effect by bile salt.
Altered haemodynamic response to haemorrhage.
Blunted vascular response to vasopressor and volume