Now would be the time to make sure you have coffee in hand.

 Understand hepatic anatomy and physiology  Understand liver’s role in metabolism  Review liver functions tests  Describe the effects of anesthesia on the liver

Dr. Lindsay Higgins will be presenting Chapter 34: Anesthesia for Patients with Liver Disease Hopefully, she will provide cookies.

 Centrilobular vein surrounded by cylinder of hepatocytes  Portal triads surround lobule Hepatic arteriole Bile duct Portal venule

 Defined by blood supply  Portal Tract at the center  Centrilobular veins at periphery  Zone 1: Near portal tract—well- oxygenated  Zone 3: Near vein— susceptible to injury

 Normal hepatic blood flow 1500cc/min 25-30% from hepatic artery 70-75% from portal vein  Oxygenation requirements supplied by both 45-50% from hepatic artery 50-55% from portal vein  Liver can act as a reservoir Normally 450 cc Can hold up to 1 Liter in cases of CHF  Portal Vein flow not regulated—susceptible to systemic hypotension

 Blood-cleansing  Metabolism of carbohydrates, fats, proteins, and drugs  Synthesis of proteins, enzymes, clotting factors

 Kupffer cells line sinusoids  Part of monocyte- macrophage system  Involved in phagocytosis, antigen processing, and release of mediators  Removes bacteria and endotoxin leaving portal circulation

 Main organ for storage and release of glucose  Glycogenesis converts glucose to glycogen Big Meal  Increased insulin  glycogenesis  Glycogenolysis breaks down glycogen to glucose Initiated by starvation, stress, or sympathetic activation  Epi or  Glucagon  glyconeolysis  Glycogen stores depleted after 24 hours

 If carbohydrate stores are saturated, carbs converted to triglycerides.  Fatty acids can be used immediately or stored for winter. Of note, RBCs only use glucose for fuel Neurons only utilize glucose except during starvation  ketone bodies  Fatty acids converted to Acetyl-CoA which then enters…

 The Citric Acid Cycle!  ATP produced  Acetyl CoA : converts to ketone bodies Utilized in cholesterol and phospholipid production

 Without the liver’s role in protein metabolism death would occur within several days  Deamination of excess amino acids  carbohydrates and fats  All plasma proteins except immunoglobulins synthesized in the liver  Nonessential amino acids synthesized

 Answer: Ammonia accumulation  Urea Cycle converts ammonia and CO 2 to Urea  excretion by kidney

 All plasma proteins except immunoglobulins  Coagulation factors Unfortunately will talk more about this  Bile formation Absorption of fat soluble vitamins

 Most drugs undergo hepatic biotransformation  Two (or three) pathways Phase I: modification of active groups by cytochrome P- 450 or mixed-function oxidases Phase II: conjugation of metabolites to water-soluble substrates  elimination via urine or bile Phase III (Baby Miller): energy dependent excretion into bile  Metabolism of certain drugs dependent on hepatic bloodflow LidocaineMorphineVerapamil LabetalolPropranolol

 Key point of drug interactions  Inducers of note: barbituates, ketamine, ethanol, phenytoin, rifampin, omeprazole, isoniazid Induction increases action  increased metabolism Patient exhibits increased tolerance to medications  Inhibitors of note: anti-retrovirals, cimetidine, chloramphenicol, fluconazole, bupropion Inhibition decreases action  decreased clearance Prolonged duration of action

 AST (SGOT)  ALT (SGPT)  Alk Phos  Albumin  Prothrombin Time  Bilirubin  INR  AST, ALT, Alk Phos measure hepatocellular integrity  Albumin, PT, INR measure synthetic function

 Bilirubin T bili (N 3 Direct (conjugated) may reflect hepatocellular dysfunction, cholestasis, or biliary obstruction Indirect (unconjugated) seen with hemolysis or defects in bilirubin conjugation Direct bilirubin is toxic to cells  Alkaline Phosphatase Produced by liver, bone, small bowel, kidneys, and placenta Majority derived from bone High levels indicate intrahepatic cholestasis or biliary obstruction

 ALT Primarily in liver  AST Present in liver, heart, skeletal muscle, kidneys AST elevating to greater extent  EtOH  Albumin Normal Half-life 2-3 weeks <2.5  chronic liver disease, acute stress, or severe malnutrition

 Measures activity of fibrinogen, prothrobin, and factors V, VII, X  Half-life 4-6 hours  Normal seconds  Prolongation of 3-4 s ~ INR of 1.5  Reflects Severe liver disease Vitamin K deficiency

 Both general and regional anesthsia Volatiles reduce portal flow (Halothane > sevo > iso) Isoflurane causes direct arterial vasodilation Neuraxial techniques decrease via lowering arterial BP General anesthesia decreases via lowering BP, reducing cardiac output, and reducing sympathetic stimulation  Positive pressure ventilation decrease blood flow through decrease in venous return  Hypoxemia reduces flow  Beta-Blockers, Alpha-1 agonists, H 2 Blockers, Vasopressin

 Levels of catecholamines, glucagon, and cortisol increase  Results in Glycogenolysis  Hyperglycemia Negative nitrogen balance  Stress response can be blunted by regional techniques, deep general anesthesia, or sympathetic blockade

 Halothane directly inhibits metabolism Phenytoin Warfarin Ketamine  Decreased hepatic blood flow decreases metabolism of other drugs Fentanyl, verapamil, propranolol

 All opioids potentially cause spasm and increase biliary pressure  Fentanyl > morphine > meperidine  Relieved by naloxone or glucagon

 May be due to reduction in blood flow, sympathetic stimulation, or surgery its self  Elevation of LFTs postoperatively usually secondary to surgery or pre-existing disease  Most common cause of post-operative jaundice is resorption of hematoma

 Halothane Hepatitis also seen with methoxyflurane, enflurane, and isoflurane Range from asymptomatic increase in LFTs (1:5) to fulminant hepatic necrosis (1:35,000)  Risk factors include Middle age Obesity Female species Repeat exposure to halothane (> if within 28 days)  Diagnosis of exclusion Eliminate pre-existing disease Viral hepatitis, CMV, herpes, etc

 I hate my life  Three processes Vascular spasm Platelet plug (primary hemostasis) Coagulation (secondary hemostasis)

 Prolonged bleeding in liver disease? Vitamin K deficiency Impaired hepatic synthesis Splenic sequestration of platelets  Normal PT, PTT, prolonged bleeding time? Platelet disorder Quantitative  thrombocytopenia Qualitative  Normal platelet count

 Most common inherited bleeding disorder? von Willebrand’s (1:800) Most heterozygous  only apparent during major bleeding Treatment  DDAVP is mild  Cryoprecipitate or factor VIII if no response  Hemophilia A Factor VIII deficiency X-linked (1:10,000 males) Prolonged aPTT, normal PT Symptomatic if < 5% activity, raise level to 50% prior to surgery  Hemophilia B (Christmas disease) Factor IX X-linked (1:100,000 males)

 Vitamin K dependent factors? II, VII, IX, X  Heparin mode of action? Promotes Antithrombin III  What’s different about LMWHs? Inhibits Xa preferentially

 Cutest kid?