Kelly's Liver Guide Exam III PDF

- Gross Anatomy - 2nd largest organ (largest in abdomen) - Glisson's Capsule - layer of connective tissue that surrounds all the ducts and arteries / protects hepatic structures - Allows the liver to fluctuate in size - Innervated - if the liver becomes...

- Gross Anatomy - 2nd largest organ (largest in abdomen) - Glisson's Capsule - layer of connective tissue that surrounds all the ducts and arteries / protects hepatic structures - Allows the liver to fluctuate in size - Innervated - if the liver becomes diseased or swollen → distention of capsule is painful - 4 lobes - right (larger), left, quadrate (bottom, near gallbladder), and caudate (top near inferior vena cava) - Right and left lobes are divided by falciform ligament - Round ligament (Ligamentum Teres) and Ligamentum Venosum are remnants of fetal circulation - Also separated into Couinaud Classification - 8 functionally independent segments - Each segment has its own vascular supply and biliary drainage → own branch of portal vein, hepatic artery, and bile duct - Cell Types - **4 main types of liver cells**: hepatocytes, kupffer cells, hepatic stellate cells, and liver sinusoidal endothelial cells - **Hepatocytes** - Most prevalent - The 'workhorses' of the liver ("responsible for many of the key functions") - Specialized, polygonal-shaped epithelial (parenchymal) cells - Make up 80% of total liver mass - Store glycogen, vitamin B12, and iron - Participate in lipid turnover and transport - Synthesize plasma proteins (albumin, prothrombin, fibrinogen) - Metabolize and detoxify fat - Turnover of steroid hormones - Regulate cholesterol - Secrete bile (up to 1 L/day) - "Specific hepatocyte function in different zones" - Apex: hepatocytes produces all clotting factors that are made in the liver (except for 8) - Myeloid cells (has to do with or resembles bone marrow): kupffer cells, dendritic cells, and suppressor cells - **Kupffer Cells** - Critical role in detoxification → they are macrophages - Constitute 80% of all tissue macrophages - Remove bacteria, viruses, proteins, and particulate matter from the blood by phagocytosis - Located in portal and lobular liver sinusoids - Dendritic cells - promote tolerance to phagocytosed particles - Suppressor cells - suppress the immune response in the liver - **Hepatic Stellate Cells** - 8-10% of liver cells - Reside in the Space of Disse - Store vitamin A and regulate sinusoidal circulation - In liver injury these cells can proliferate → myofibroblasts → hepatic inflammation and fibrosis - "Portal vein is 8-10 and exiting vein is 4-8 → increase in resistance (inflammation, etc.) → blood finds another way to go → shunting → stops the normal functions due to blood flow not reaching important areas → then fibrosis worsens → blood backs up into hepatic circulation (lower pressure) → varices, etc. " - **Liver Sinusoidal Endothelial Cells** - Interface between blood cells on one side - hepatocytes and stellate cells on the other - Represent a permeable barrier - Regulate hepatic vascular tone - Lobules - anatomic unit of the liver - Liver consists of 50,000 - 100,000 tubules - Each lobule is composed of: - Portal triad: - Branch of hepatic artery - Branch of portal vein - Bile ducts - Plate of Hepatocytes - Central Vein (CV) - Each lobule is constructed around a central vein and consists of cellular plates that radiate from a central vein like spokes in a wheel - Cellular plates surround bile canaliculi → empty into bile duct - Blood comes in from aorta (HA) and gi tract (PV) → flow into sinusoids (here the blood mixes) → the lining of the sinusoids have large pores that allow plasma and proteins the flow through into → Space of Disse - where blood is cleaned/filtered, excess fluid and waste products are drained via lymphatic duct → empties into central vein → hepatic vein → IVC → RA - Space of Disse: between sinusoidal capillaries and hepatocytes - Nutrient exchange (contains stellate cells with vitamin A) - Kupffer cells (filter) - Acinus - functional unit of the liver - Zone 1: periportal - Hepatocytes closest to blood supply (well oxygenated) / closest to portal triad - Responsible for 'high' oxidative activities - gluconeogenesis, oxidation of fatty acids, cholesterol synthesis, bile formation - Zone 2: midzone - Centrally-located hepatocytes - Zone 3: perivenous or pericentral - Hepatocytes are the furthest away from blood supply (closer to central veins) - MOST susceptible to ischemic injury - Responsible for glycolysis, lipogenesis, detoxification, "and biotransformation of drugs" - Hepatic Blood Flow / Hepatic Circulation - 25% of resting cardiac output (800-1200 ml/min) - Total hepatic blood flow = portal vein blood flow + hepatic artery blood flow - Hepatic blood flow serves two distinct purposes: - 1\. Supply the organ itself with necessary oxygen and nutrients (HA \> PV) - 2\. Provide all the services to the rest of the body (PV \> HA) - Dual afferent blood supply - Hepatic artery - Arises from celiac artery (80% of the time) or SMA (20% of the time) - Pressure = aortic pressure (90 mmHg) - 25 - 30% of blood supply - 50 - 70% oxygen requirements - How is this different from other organs? - most organ receive all oxygen from arterial supply - Why? - because not all of the blood going to the liver is there to provide oxygen / nutrients to the organ itself - Portal Vein - "drains from GI tract - rich in nutrients and bacteria" - Arises from SMA, IMA, and aorta - Pressure is lower (6 - 10 mmHg) - 70 - 75% of blood supply - 30 - 50% of oxygen requirements - This blood is lower in oxygen content, but high in stuff that needs to be transformed into a usable form or eliminated - How does blood exit the liver? Hepatic veins → IVC - Sympathetic stimulation (hypoxemia, catecholamines, hypercarbia) → increases hepatic artery vasoconstriction AND vasoconstriction of splanchnic circulation → end result: decreased hepatic blood flow - Beta-2 stimulation → vasodilation, relaxation of smooth muscle - relaxation of GI smooth muscle → increases liver's ability to make glucose and increases hepatic blood flow via vasodilation of hepatic artery - Beta receptors are only in the hepatic artery (not portal vein) → beta-2 stimulation doesn't change portal venous supply - Beta blockers → reduce hepatic artery blood flow and decrease portal pressure - Vasopressin → reduces splanchnic blood flow and decreases portal venous pressure - Intrinsic determinants of hepatic blood flow - hepatic artery buffer response - "Take home: one sided, adenosine, can adjust to 100%, stopped by volatiles" - In addition to "classic arterial autoregulation" where changes in blood pressure causes constriction or dilation of hepatic artery, the liver can regulate its own blood supply via the hepatic artery with the hepatic artery buffer response - "second form of intrinsic regulation" - Hepatic artery tone adjusts to changes in portal flow - mediated by adenosine - Hepatic artery flow can increase as much as 100% to maintain oxygen delivery to the liver - Decrease in portal vein flow → low pH, low CO2, elevated CO2 → increased adenosine → hepatic artery vasodilates - "Great protective response → but our meds mess it up → another reason why MAP is important" - Volatiles and cirrhosis interfere with this response (but it does work during laparoscopic cases) - Portal vein does NOT compensate for changes in hepatic artery supply - Why does this matter? - 1\. Maintains oxygen supply to the liver - 2\. Portal venous changes don't really affect the liver's ability to do its job - metabolic homeostasis is maintained - Extrinsic determinants of hepatic blood flow: - Hepatic perfusion pressure - MAP - Hepatic Vein Pressure - OR - Splanchnic Vascular Resistance - Splanchnic vessels are innervated by the SNS - SNS stimulation increases splanchnic vascular resistance → decreases hepatic blood flow - Hepatic Blood Flow is reduced with - "anything that stimulates the SNS" - Pain and/or surgical stimulation - Hypoxia - Increased catecholamines - Volatile anesthetics and regional anesthesia - Positive pressure ventilation - Excess fluid administration - Insufflation - Functions of the Liver - The liver is the body's "chemical factory" - estimated 500 separate functions to maintain homeostasis - The liver has substantial reserves, you could lose 80% of the organ and still maintain normal function AND it can regenerate - "If you have altered liver function tests, this would likely be late in the disease process due to its reserves" - Filtration and Storage of Blood - Liver normally stores approx. 450 ml of blood - Liver is expandable and store up to 1 L → reservoir in hypervolemia (excess IVFs, renal and heart failure) - This explains why we see hepatomegaly in CHF - Moderates hypotensive response to hemorrhage/hypovolemia - Forms approx. 50% of body's lymph - Kupffer cells are effective phagocytic macrophages - Liver is our "Mr. Clean" - filters 99% of bacteria entering portal circulation - Metabolism of Carbohydrates, Proteins, Fats, and Drugs - Carbohydrate Metabolism - "know these terms" - Carbohydrates - storage and release of glucose (glucose buffer function) - GlycoGENESIS: converts glucose → glycogen to store in liver for later use - Approximately 75-100 gram - still not the body's biggest store of glycogen (skeletal muscle is) - "Important for long distance runners - beforehand you carb load so that you have a bigger storage of glycogen → now think about NPO patients and those with nutritional issues" - Glycogen stores can be depleted 24-48 hours of starvation - GlycoGENOLYSIS: breaks down glycogen stores → glucose when needed - Epi, glucagon, thyroid hormone, and glucocorticoids enhance glycogenolysis - Lipogenesis: converts excess glucose into fat → can be used for fuel or be stored in adipose tissue or liver for later - Gluconeogenesis: conversion of lactate, glycerol, and amino acids → glucose when glycogen stores are depleted - "from non-carbohydrate sources" - Conversion of galactose and fructose to glucose - Makes glucose from fat and proteins → helps maintain normal glucose levels - "Ammonia (from the deamination of proteins into energy) - if we can't clear ammonia → hepatic encephalopathy" - "Probably be a question: does ammonia level correlate with the level of hepatic encephalopathy? No it doesn't!!" - "Ammonia in the brain causes an increase of water into the cells → increased ICP → decreased CPP" - Fat Metabolism - Liver produces bile - needed for digestion of fat and production of cholesterol - Oxidation of fatty acids to CoA (acetyl coenzyme-A); excellent energy source - Synthesis of cholesterol, phospholipids and most lipoproteins - Synthesis of fat from proteins and carbohydrates to be stored in adipose tissue - "What you need to know: liver is responsible for a major part of fat metabolism" - Protein Metabolism: - Deamination of amino acids to carbohydrates or fat; formation of urea for removal of ammonia - Liver produces ALBUMIN, ANGIOTENSINOGEN, THROMBOPOIETIN, PLASMA CHOLINESTERASE - ALL plasma proteins except gamma globulins & factors III, IV and VIII - Liver produces albumin 10-15 g/day accounts for over 50% of total plasma protein - Transports lipids and hormones, maintains blood volume, normal = 3.5-5.5 g/dl - "maintains intravascular volume and binds our drugs" - Low albumin means less is available to bind to our drugs → more unbound/active medication levels in the body → increased Vd and increased sensitivity - Half time of albumin in the body is about 23 days - "is the liver issue is being evaluated, if the albumin is normal its likely an acute problem, but if its low it\'s likely chronic" - VITAMIN K is required for synthesis of prothrombin (II) and factors VII, IX, and X - Amino acid synthesis - (glutamate, glutamine, alanine, asparagine, aspartate, glycine, serine, homoarginine) - Liver enzymes convert ammonia into urea → excreted in the urine - "Liver patients you take care of - impaired clotting except for... the ones not made in liver - VIII will be high" - Drug Metabolism: - Biotransformation of drugs into inactive H2O-soluble substances that can be excreted in urine or bile - Phase I Reactions: mediated by cytochrome p-450 (oxidation, reduction, hydrolysis) - "Convert lipophilic → hydrophilic" - Phase II Reactions: conjugation (glucuronidation, acylation, sulfate, glycine) - "Combines molecules with something hydrophilic to make it able to be excreted" - Intrinsic metabolic clearance: fraction of drug that is metabolized/extracted on a single-pass through the liver - High clearance drugs are readily cleared; hepatic blood flow WILL affect clearance - "will have significant difference between the PO and IV dose" - Low clearance drugs are not readily cleared: hepatic blood flow WILL NOT affect clearance - High clearance drugs = lidocaine, diphenhydramine, metoprolol, labetalol, meperidine, morphine, warfarin - Low clearance drugs = diazepam, acetaminophen, ASA, - Synthesis and Metabolism of Hormones - The liver is responsible for the production of several hormones - 25-hydroxyvitamin D - Insulin-like growth factor - Angiotensinogen (RAAS) - Thrombopoietin (regulates platelet production) - The liver also regulates the balance of/inactivates other hormones: thyroxine, estrogen, cortisol, and aldosterone - If the endocrine system is overactive, the liver can increase it's inactivation and removal to maintain balance - Liver disease is often associated with thyroid dysfunction, hypothyroidism, issues with glucose regulation, inadequate glucocorticoid production, and systemic inflammation - Elimination of Foreign Chemicals and Toxins - Bacteria / Viruses / Cellular Debris - Kupffer cells (macrophages) \ Iso (0.2%) \> Des (0.01%) - Halothane is not longer available in the US - still used in developing countries - Two distinct suspected manifestations: - Elevated LFTs without evidence of liver failure - due to combination of halothane and hypoxia? - Severe ALF - immune mediated process? - Infection (presumably Hepatitis A and B) - Alcoholic hepatitis - Pregnancy-related - Hyperemesis Gravidarum - 1st trimester, emesis that warrants IVFs; elevated liver enzymes in up to 50% - Intrahepatic Cholestasis - 2md or 3rd trimester; impaired bile acid transport in lobule; high-risk pregnancy - Preeclampsia (HTN, Edema and Proteinuria) - 3rd trimester; "treatment is to deliver the baby" - Elevated aminotransferases = severe preeclampsia - HELLP syndrome: Hemolysis, Elevated Liver Enzymes, Low Platelet Count; treatment is to deliver the baby - AFLP: Acute Fatty Liver of Pregnancy - 3rd trimester; fatty infiltration of the liver that causes portal HTN and hepatic encephalopathy; treatment is to deliver the baby - Chronic: - Alcoholic liver disease - Non-alcoholic fatty liver disease - Caused by excessive fatty deposits in the liver - Ranges in severity from steatosis (simple fat deposits) → steatohepatitis/NASH (hepatocellular necrosis) - Associated with metabolic syndrome - Insulin resistance - Obesity - Central Adiposity - Type-II Diabetes - HTN - Elevated triglycerides - Most common cause of elevated liver enzymes in adults - NASH: Liver biopsy shows steatosis with inflammation and fibrosis - Treatment: weight loss (bariatric surgery) - Acute vs Chronic Hepatitis: - Acute Hepatitis - - Hepatocellular injury due to viral infection, drug reaction or exposure to hepatotoxin - Acetaminophen - Alcohol - Mushrooms - Chronic Hepatitis - - Lasting \>6 months - Lab values do not correlate with disease severity - Liver biopsy -\> classification into one of three types - Chronic Persistent Hepatitis - Chronic Lobular Hepatitis - Chronic Active Hepatitis- \*assume cirrhosis - "Hepatitis C - most likely to develop into chronic liver failure" - Hepatocellular Carcinoma - Most common primary liver malignancy - 3rd most common cause of death globally - Men \> women - Risk: - Treatment: - Treatment for non surgical patients: - "Typically have an ultrasound every 6 months" - Cholestatic / Post-Hepatic (increased conjugated bilirubin; AST/ALT if late dx; AP, GGTP, and 5'-NT; decreased albumin late dx) - Biliary disease - affects \> 20 million in the U.S. - Causes: - Biliary obstruction - Cholestatic disease - Chronic: - Impaired bile flow increases biliary pressure and backflow into liver → hepatocyte destruction - If bacteria in bile → ascending cholangitis, hepatic abscess, sepsis, and acute kidney injury can occur - Deficiencies in Vitamin K-dependent clotting factors (II, VII, IX, X) - Hypercoagulability - S&S: fatigue, pruritus, dark urine, pale stools - Diagnosis: Abdominal US to determine extrahepatic vs. intrahepatic cause - Extrahepatic causes: bile duct obstruction by stone, stricture, mass - Intrahepatic causes: immune-mediated, infectious, drug-induced, paraneoplastic, ischemic - Labs: Elevated serum AP and GT; may have elevated bilirubin - Check AMA (antimicrobial antibody) titers to rule out Primary Biliary Cholangitis - Treatment: Endoscopic Retrograde Pancreatography (ERCP) - Primary biliary cholangitis (PBC) - autoimmune "no test questions" - Primary sclerosing cholangitis (PSC) - autoimmune "no test questions" - Sepsis - Cirrhosis - **End-result** of chronic liver diseases - Lobules are replaced with fibrosis and regenerative nodules - "What zone cells are most susceptible to ischemia? Zone 3 → these are responsible for glycolysis, lipogenesis, and detoxification / biotransformation" - Disrupts blood flow thru liver → leading to shunt formation → "blood backs up into portal venous circulation" → Portal HTN, Esophageal Varices, Ascites Hepato-renal syndrome (HRS), Pulm HTN - Increased hepatic resistance and intrahepatic vasoconstriction- portal pressure continues to increase → portal HTN - Body responds with splanchnic vasodilation → causes a decreased effective arterial circulation - Now the SNS and RAAS get activated → leads to sodium and water retention, hypervolemia, increased CO - viscous cycle - S&S: - Jaundice, thrombocytopenia, bleeding, endocrine abnormalities, diabetes, hepatocellular carcinoma - Labs: - Increased ALT, AST, AP, GGT, bilirubin, PT, - Decreased albumin - Causes: - Alcoholic Liver Disease - Chronic Hepatitis - Nonalcoholic Steatohepatitis Hemochromatosis - Wilson's Disease - Primary Biliary Cirrhosis - Primary Sclerosing Cholangitis - Alpha-1 Antitrypsin Deficiency Prolonged Cholestasis - Toxins / Drugs - Hepatic Venous Outflow Obstruction - Cystic Fibrosis - Treatment: depends on disease severity - Multiple Systems are affected: - Coagulation - Hemostasis - mechanisms at play affecting both intrinsic and extrinsic pathways - \*\*\*Leads to disrupted balance between bleeding and clotting\*\*\* - Decreased synthesis of both clotting and inhibiting factors - Decreased synthesis of Vitamin-K dependent clotting factors (II, VII, IX, X) - Especially in cholestatic diseases (bile salts are needed for absorption of Vitamin K) - Liver synthesizes all procoagulant and anticoagulant factors EXCEPT: III (thromboplastin), IV (calcium), and VIII (VWB) - Liver is also how activated clotting factors are cleared from the body - Vitamin K administration can correct this - Decreased synthesis of thrombopoietin → leads to thrombocytopenia → low and dysfunctional platelets - Decreased synthesis of inhibiting factors (protein C, protein S, antithrombin III,) - Increased consumption of platelets and clotting factors - Decreased clearance of activated factors - Hyperfibrinolysis - Accelerated intravascular coagulation/DIC - Renal dysfunction / Hepatorenal Syndrome - Sodium and water retention - Renal hypoperfusion and decreased GFR - Increased prostaglandin levels help maintain renal perfusion - "caution w/ meds that affect prostaglandins - no NSAIDS" - Increased sensitivity to nephrotoxic drugs: - Aminoglycosides - ACE-Inhibitors - ARBs - Definitive treatment: Transplant (in severe cases - combined liver and kidney transplants) - Hepatic encephalopathy - Seen with both acute and chronic liver disease - Result of accumulated neurotoxins (commonly ammonia, but can occur without it) - Neuropsychologic and neuromotor symptoms - Neuropsychological Symptoms: - Impaired LOC and attention - Impaired ability to follow commands - Altered affect - Neuromotor Symptoms: - Hyper-reflexiveness (Asterixis, Clonus, Babinski) - Nystagmus - Decerebrate posturing - Cirrhotic cardiomyopathy - Liver disease patients (cirrhosis) have hyperdynamic circulation - "take home message" - High cardiac output - Low BP (systolic and diastolic dysfunction) - "especially post induction" - Low SVR (from release of nitric oxide) - Increased overall fluid volume with decreased circulating volume - Decreased responsiveness to beta-adrenergic stimulation - Prolonged Q-T interval - Dr. Schlesinger's Notes: portal HTN causes release of vasodilators (esp. NITRIC OXIDE)... "overproduction of vasodilators" means sympathetic responsiveness is less effective - Pulmonary complications - Hepatopulmonary Syndrome (HPS) - Affects up to 20% of liver transplant patients - **Triad** of liver dysfunction, unexplained hypoxemia and intrapulmonary vascular dilation - Intrapulmonary vascular dilation (IPVD) - Type I lesions: precapillary dilations = functional shunts - Type II lesions: larger dilations in central lungs = anatomic shunts - Post Pulmonary HTN - Affects 4-6% of liver transplant patients - Pulmonary HTN in a patient with portal HTN - Increased risk in female patients and autoimmune hepatitis - Hepatic Hydrothorax (HH) - Ascites fluid passes from peritoneal cavity into pleural space thru defects in the diaphragm - Dr. Schlesinger's Notes: - Other causes: **Cystic fibrosis and A1 Antitrypsin Disease -** metabolic syndrome (Lung and Liver consequences) - Ascites - "Remember they are 'puff balls' and seem fluid overloaded but are intravascularly dry" - Associated with a 50% mortality within 3 years - Infections common - Treatment: - Paracentesis + slow correction of hyponatremia - Needed with serum Na+ is \< 120-125 - If corrected too quickly: central pontine myelinolysis - Sodium restriction - Diuretics - Albumin replacement if \> 6-8 L drained by paracentesis - Varices - End result of portal HTN - Treated with beta-blockers to decrease portal pressure and endoscopic ligation - Decrease portal pressure by: decreasing CO and decreasing splanchnic vasoconstriction - Pre Op Assessment - Risk factor assessment: alcohol and/or illicit drug use, herbal medication use, transfusion history, tattoos, sexual promiscuity, consumption of raw seafood, travel to endemic areas - "looking to diagnose, don't ask your patients all of this" - Signs & Symptoms: jaundice, fatigue, anorexia, weight loss, N/V, easy bruising, dark-colored urine, biliary colic, abdominal distention, GI bleeding, loss of appetite, fatigue, malaise, difficulty sleeping, subtle cognitive changes, pruritus, easy bruising, changes in color of urine or stool - "this is what you should look for if you know your pt has liver dx" - Physical Exam Findings: Jaundice, Scleral Icterus, Ascites, Spider Angiomas, Xanthelasma, Asterixis, Palmar Erythema - Spider Angiomas: vascular lesions just beneath the skin that result from abnormal dilatation of vasculature - Isolated ones are benign, but multiple ones are characteristic of chronic liver disease (95% specificity) - Also suggest a high likelihood of varices and HPS - Xanthelasma: sharply demarcated yellowish cholesterol deposits under the skin - Considered an ocular manifestation of liver disease - Believed to be due to inflammation - Asterixis: floppy hands or "liver flap" or "hepatic flap" - Lab values: Routine screening LFTs not indicated, Avoid testing in asymptomatic patients - Preop LFTs: - Elevated ALT and AST in asymptomatic patient: proceed if \< 2x normal and normal alk phos, bilirubin, INR - Transaminases \> 2x normal → workup prior to elective surgery (US, CT, liver biopsy) - Both transaminases and INR abnormal → workup prior to elective surgery (US, CT, liver biopsy) - Elevated alk phos and elevated transaminases → suspect biliary disease and workup indicated - Child-Pugh Risk Assessment - "only know what it is, not specifics" - Scoring criteria to assess the severity of liver disease - Based on 5 factors: encephalopathy, ascites, bilirubin, albumin, and INR - Patients can be scored an A, B, or C (C being the worst) - MELD: Model for End-Stage Liver Disease - "just know it's objective, and that it doesn't include the cause of liver disease" - Creatinine, Bilirubin, INR, and Sodium - now whether they're on dialysis or not is included as well - Used to predict 3 month survival in liver disease patients - used to allocated transplants - Optimize Preoperative Status - Least invasive surgical options are preferred! - "the more you're in the abdomen the more you affect your bf to the liver" - Optimize nutritional, renal and cardiac function - Treat ascites - Optimize albumin levels - Correct coagulation and electrolyte disturbances - Treat encephalopathy (lactulose and oral antibiotics) - Maintain cardiac output (to maintain hepatic blood flow!) - Be vigilant for alcohol withdrawal in patients with alcoholic liver disease - Perioperative Management - Altered Pharmacokinetic Considerations - Altered protein binding - reduced albumin levels and other drug-binding proteins - Altered volume of distribution associated with ascites and increased TBW - Reduced metabolism - "decreases doses of systemic medications" - Potentiation of anticoagulants (decreased production of clotting factors) - Altered drug elimination - Altered enzymatic activity - Altered hepatic extraction - Low albumin - Impaired oxidative metabolism - Conjugation relatively unaffected - Biliary excretion depends on degree of intrahepatic shunting - Overall: decrease the doses (50%) in systemic meds - Patients with liver disease commonly have an increased volume of distribution, necessitating an increase in initial dose - However, because the drug metabolism may be reduced, smaller doses are subsequently administered at longer intervals - General - Induction of General Anesthesia - Monitoring (AL, PAC, TEE, TEG or thromboelastography) - Thromboelastography (TEG): evaluating actual function not just specific levels of individual factors - Anticipate increased aspiration risk, rapid desaturation and hypoxemia - preoxygenate and RSI - Propofol, Etomidate and Midazolam do not alter hepatic artery perfusion when given for short procedures - Anticipate increased susceptibility to CNS-depressant effects. - Prolonged infusions of propofol have been associated with (rare) syndrome of lactic acidosis, lipemia, rhabdomyolysis, hyperkalemia, cardiac failure and death - Increased susceptibility to CNS-depressant effects - Induction Agents - Methohexital / Ketamine / Etomidate / Propofol: - Highly lipid-soluble and high hepatic extraction ratios → expect decreased clearance in liver disease - BUT clearance is mostly unaltered in cirrhosis - Increased VD may prolong elimination - Recovery times after propofol infusion in cirrhotic patients may be prolonged - Dexmedetomidine - Liver metabolism primarily with little renal clearance - Decreased clearance and prolonged half-life - Midazolam - Reduced clearance prolongs elimination half-life - Infusion is a bad choice due to prolonged elimination - Benzodiazepines are metabolized in the liver by microsomal oxidation and glucuronidation - Should be used with caution in the elderly - "Use extreme caution in these patients as well" - The potency, onset, and duration of action of benzodiazepines depend on their lipid solubility - Lorazepam undergoes phase II glucuronidation - normal metabolism with liver disease - Propofol, ketamine, and etomidate - high hepatic extraction ratio, pharmacokinetics are unchanged in mild-mod cirrhosis - Although pseudocholinesterase levels are decreased in patients with liver disease, the clinical prolongation of succinylcholine is not significant - still avoid if patient is hyperkalemic - Maintenance of General Anesthesia - Monitoring and IV access - depends on preexisting disease, surgical procedure - Maintain cardiac output and hepatic blood flow - Avoid hypocapnia - Hematologic considerations - perioperative bleeding - Meticulous fluid management (albumin!) - Avoid hypothermia - "increase workload on the heart" - Increased susceptibility to CNS-depressant effects - Nitrous oxide - appears ok as long as not used in the setting of impaired hepatic oxygenation - Vitamin K? Do they need vitamin k administration to help improve their clotting factors? - Platelets? Goal \> 50k - Fibrinogen? - Opioids - "over all cautious dosing, risk of prolonged effect" - Morphine: prolonged half-life in advanced liver disease; exaggerated sedative effects, resp. depression - Meperidine: reduced clearance, half-life is doubled, reduced clearance of normeperidine (active metabolite) - Hydromorphone: prolonged half-life, exaggerated sedative effects and respiratory depression - Fentanyl: Good choice for patients with hepatic disease, elimination not significantly altered in cirrhosis - High lipid solubility with short duration of action; repeated dosing/ infusion may see prolonged effects - Sufentanil: high lipophilicity, highly protein-bound, extensively metabolized by liver, pharmacokinetics not appreciably altered in cirrhosis - Alfentanil: higher free fractions in cirrhosis can prolong action and exaggerate effects - Clearance unaffected by hepatic function - Remifentanil: Ester linkage; metabolism by hydrolysis (tissue and blood esterases), unaffected by hepatic function - Remember to dose long-acting drugs prior to discontinuation of infusion - Antibiotics are low extraction drugs (not affected by hepatic blood flow) - may be affected by decreased protein binding - Additional Considerations: - Maintain hepatic blood flow - Anything that decreases CO will decrease hepatic blood flow - Not just meds and low bp → think PPV, high airway pressure, insufflation, positioning (steep t-berg) - VAs: Decrease MAP = decrease portal blood flow → MAINTAIN MAP! \*\* "was an issue last semester" - assuming this means its a test question\*\* - ISO may actually increase HA blood flow and is preferred vs. Sevo? - Induction agents: Propofol, Thiopental, Etomidate, Methohexital do NOT adversely affect the liver beyond decreased HBF - Benzodiazepines: Prolonged ½ life; reduce dosages! - NMBAs: Prolonged DOA with vecuronium and rocuronium- monitor TOF - Succinylcholine DOA may be prolonged due to decreased plasma cholinesterase (earlier in her notes she says it's not enough to care) - Vec and roc may be prolonged with extrahepatic biliary obstruction - Opioids: Morphine, Meperidine, Alfentanil metabolism is decreased - Effects can be prolonged and contribute to post op respiratory depression - Vasopressors: Reduced responsiveness to pressors and catecholamines - Extraction ratio is the amount of drug that is eliminated during a single pass through the liver. - If no drug is eliminated on the first pass, the extraction ratio is 0 - If all of the drug is eliminated on the first pass, extraction rate is 1 - What factors do you think determine the hepatic extraction ratio? - Hepatic blood flow, Fraction of unbound (free) drug, and ability of hepatocytes to metabolize a drug - Drugs with high extraction ratios are rapidly cleared and **clearance is highly dependent on hepatic blood flow** (Propofol, Fentanyl, Morphine, Labetalol, Propranolol) → reduce dose but not frequency - Neuraxial - May be contraindicated due to existing coagulopathy and/or thrombocytopenia - Reduce doses in advanced liver disease - Epidural anesthesia can be used in lower abdominal and limb surgeries - Avoid hypotension - need to maintain hepatic perfusion - Avoid high neuraxial block (T-5) - associated with decreased hepatic blood flow - Peripheral Nerve Blockade - No negative effects on HBF or liver function - Remember some LAs are metabolized by the liver - Esters - hydrolysis by pseudocholinesterase in plasma - Amides - biotransformation in the liver - Procedural Considerations - **Liver biopsy** is the method of choice to determine whether liver damage is due to necrosis, inflammation, steatosis, or fibrosis - Coagulopathy or thrombocytopenia contraindicates percutaneous liver biopsy - TIPS: Transjugular Intrahepatic Portosystemic Shunt Procedure - [she read the name like 3x so idk what that means] - Interventional encephalopathy procedure - Hepatic vein is accessed via internal jugular vein and shunt is placed between hepatic vein and portal vein (bypasses liver) - Used primarily to treat bleeding esophageal varices and refractory ascites - Risks: hemoperitoneum, inadvertent formation of shunt between hepatic artery or bile ducts and portal vein, worsening encephalopathy - Dr. Schlesinger's Notes: - TIPS is done for patients with ascites and esophageal varices - SHUNT PLACED to bypass the liver (portal vein to hepatic vein) - Hepatic Resection - Major hepatectomy : resection of 3 or more segments - Complications: - Bleeding - Vasopressors can decrease blood loss (by decreasing splanchnic pressure) - Portal triad clamping of afferent vessels - Total vascular occlusion (portal triad plus IVC) - Ischemic preconditioning (occlusion, reperfusion, clamping) - Air Embolism - Increased risk if tumor is near vena cava or involves portal vessels - Postop: Pleural Effusions, Biliary leakage, Wound dehiscence, Ascites, Abdominal abscess - Alcoholism and Anesthesia - Malnutrition and dehydration - Decreased resistance to infection, delayed wound healing - Liver Damage: Monitor labs to assess severity, use scoring systems - Pulmonary Complications: many alcohol abusers also smoke, may have COPD or HPS - Cardiomyopathy: arrhythmias common - Renal disease: may have glomerulonephritis or HRS - Neurological disease: neuropathy, DTs, or acute intoxication - **Cross tolerance to medications is common!** - Benzodiazepines and other sedatives stimulate the same receptors as many of our anesthetics - Patients with ESLD may be more sensitive to our medications if the liver is not able to eliminate the medication - Chronic alcoholics may have cardiomyopathy and dysrhythmias, may be predisposed to aspiration, and may have diminished pulmonary function - They may have impaired synthetic liver function - important screening tests are albumin and prothrombin time - Alcohol withdrawal may cause seizures - "may start as tachycardia then lead to seizures" - Acute ETOH Intoxication - Acutely intoxicated - Decreased MAC - Aspiration d/t decreased gastric emptying and decreased LES tone - Alcoholic (not acutely intoxicated) - Increased MAC - Alcohol withdrawal syndrome - Tachycardia, agitation, increased SNS tone 48-72 hours after last alcohol intake - Tremulousness and hallucinations, hyperpyrexia, cardiac dysrhythmias - grand mal seizures - Severe withdrawal (Delirium Tremens) is a medical emergency - Porphyrias - Rare genetic aberrations in heme production - Heme production required 8 different enzymes - genetic deficiency in one of these results in porphyria - Accumulation of porphyrins in tissues leads to porphyrias - Due to a buildup of naturally occurring chemicals that are necessary for the function of hemoglobin - Acute Intermittent Porphyria: - Incidence: 1:10,1000 in general population (most common) - S&S: recurrent serious neurologic reactions, abdominal pain, dark urine, HTN - Can be life-threatening - Triggers: barbiturates, sex hormones, glucocorticoids, cigarettes, other meds (ketorolac, phenytoin, birth control pills, sulfonamides, benzodiazepines (possibly), ketamine (possibly)) - Cutaneous Porphyria: porphyrins build up in skin - Symptoms occur skin is exposed to sunlight