NA 731 Hepatic Pathophysiology Fall 2022 PDF

# NA 731 Pathophysiology for Nurse Anesthesia II Fall 2022 ## Hepatic Pathophysiology ### Epidemiology - 4.5M Americans live with liver disease - 40,000 deaths/year due to liver disease in the US - Viral infectious hepatic disease has decreased with modern therapy - Both alcohol and nonalcohol-rel...

# NA 731 Pathophysiology for Nurse Anesthesia II Fall 2022 ## Hepatic Pathophysiology ### Epidemiology - 4.5M Americans live with liver disease - 40,000 deaths/year due to liver disease in the US - Viral infectious hepatic disease has decreased with modern therapy - Both alcohol and nonalcohol-related liver disease have increased ### Liver functions - Central to numerous metabolic and physiologic processes - Patients with liver dysfunction are at an increased risk for perioperative morbidity and/or mortality due to failure of one of the liver's essential functions - **Metabolic functions:** - CHO metabolism → moderates gluconeogenesis and glycogenolysis - Protein synthesis, including plasma proteins that bind drugs as well as proteins as well as proteins like plasma cholinesterase (this is NOT referring to atypical plasma cholinesterase) - Drugs like succinylcholine and ester local anesthetics will have a longer DOA - Protein metabolism - Bilirubin metabolism – bilirubin is conjugated so it can be incorporated into bile - Bile production - produced by each lobule continuously, stored in GB, released in response to CCK → required for metabolism of fat-soluble vitamins and minerals (A, D, E, & K) - Increased risk for bleeding 2/2 decreased amounts of Vitamin K dependent factors - Insulin clearance - removed with first portal pass - Drug metabolism - Phase 1 and Phase 2 reactions → CP450 system is crucial - **Hemostasis** - synthesizes coagulation factors and other proteins involved in hemostasis ### Liver Blood flow - 25% of cardiac output when portal and hepatic flow are considered - **Portal vein** - confluence of splenic vein and SMV → 75% of flow, with 50% of O2 supply - **Hepatic artery** - only 25% of blood flow, but supplies 50% of O2 - Regulated by intrinsic and extrinsic mediators - If portal flow decreases, hepatic artery flow increases only works one direction - Portal vein flow will not change if hepatic artery flow decreases - With elevated portal pressure, portosystemic shunts form, which lead to the development of varices ### Liver Anatomy - **Lobe:** portion of the liver - **Right | Quadrate | Caudate | Left** - **Segment:** a further subdivision of the lobe ### Liver Assessment - **History/Physical:** RF for liver disease, severity of findings, and comorbidities - RF: family history, alcohol use, DM obesity, IV drug use, tattoos (2/2 HepC risk), transfusions, hepatotoxic drugs - Assess for fatigue, pruritis, bleeding/bruising, volume overload, weight change (esp weight gain), dark urine - **Lab Data:** - Comparison will result in identifying the type of dysfunction present - **Liver Chemistry:** - **Aspartate aminotransferase (AST): Alanine aminotransferase (ALT):** Acute liver dysfunction will have an AST:ALT ratio of at least 2:1, while it is 1:1 with nonalcoholic steatohepatitis - **Alkaline Phosphatase, gamma-glutamyltransferase (GGT), and bilirubin levels are useful to determine cholestasis o CBC & Coagulation studies** ### Causes of Hepatic Dysfunction Based on Liver Chemistry Test | Hepatic Dysfxn | Bilirubin | Aminotransfera se Enzymes | Alkaline Phosphatase | Causes | |---|---|---|---|---| | Prehepatic | Increased unconjugated fraction | Normal | Normal | Hemolysis, Hematoma resorption, Bilirubin overload from transfusion | | Intrahepatic (hepatocellular) | Increased conjugated fraction | Markedly increased | Normal to slightly increased | Viral infection, Drugs, Alcohol, Sepsis, Hypoxemia, Cirrhosis | | Posthepatic (cholestatic) | Increased conjugated fraction | Normal to slightly increased | Markedly increased | Biliary stones/tumors, Sepsis | ## Diseases of the Biliary Tract & Bilirubin ### Cholelithiasis - Occurs when substances in bile become hardened within the gallbladder, due to oversecretion of cholesterol, excess bilirubin, or hypomotility of GB - RF: obesity, hypercholesterolemia, family history, diabetes, pregnancy, female gender - 80% are asymptomatic → common symptoms are pain, nausea, vomiting, and indigestion - Can have right shoulder referred pain - Can develop sepsis - **Anesthetic implications:** - Consider opioid use within context of the Sphincter of Oddi → can antagonize a spasm with naloxone, glucagon, or a nitrate ▪ - Will likely be a laparoscopic case - Consider aspiration risk secondary to N/V ### Choledocholithiasis - Complication of cholelithiasis where a stone blocks the common bile duct - Presentation is often as biliary colic → pain in RUQ with intermittent nausea and vomiting - Can lead to cholangitis, with associated fever, rigors, and jaundice in addition to previously identified symptoms • - **Treatment:** - ERCP with endoscopic sphincterotomy - Exploratory laparoscopy/LC, with or without IOC ### Hyperbilirubinemia 1. **Unconjugated (indirect) hyperbilirubinemia** results from imbalance between synthesis and breakdown of bilirubin 2. **Conjugated (direct) hyperbilirubinemia** results from reflex of direct or conjugated bilirubin into the blood following a biliary obstruction ### Gilbert Syndrome - inherited disorder that results in unconjugated hyperbilirubinemia - Experience jaundice, fatigue, pain with dehydration, stress, fasting, or exercise ### Crigler-Naijjar Syndrome - severe, very rare inherited disorder that can result in brain damage if untreated - TX: transfusions and phototherapy - S&S: severe jaundice, fever, and vomiting ## Benign Postoperative Intrahepatic Cholestasis - multifactorial problem that is associated with hypotension, large blood loss, transfusions, or hypoxemia ## Hepatitis ### Viral Hepatitis - Most often caused by hepatitis A, B, C, D, and E, abbreviated as HXV - Each causes an acute infection that can result in significant morbidity - HBV and HCV are associated with chronic disease states, both of which commonly result in a need for hepatic transplantation HCV is the most common viral agent that leads to hepatic transplantation in US | Five Types | Hepatitis | |---|---| | A | RNA | | B | DNA | | C | RNA | | D | RNA | | E | RNA | - New therapies result in a clearance of up to 99% of viral loads certain types of HCV - Harvoni: combination drug made by Gilead Pharmaceuticals ### Alcohol-related liver disease - #1 indication for liver transplantation in the US and world - Patients often asymptomatic with ALD and with early/compensated cirrhosis - Associated with malnutrition, muscle wasting, and parotid gland hypertrophy - Physical exam with advanced disease will reveal jaundice, ascites, hepatosplenomegaly, and peripheral edema . Consider how chronic alcohol abuse will affect your anesthetic → what are your concerns now? ### Steatohepatitis - Chronic: greatly increases MAC requirements → increased risk for recall - Acute intoxication: decreased MAC requirements - AKA Nonalcoholic Fatty Liver Disease - Excessive accumulation of fat in the liver without a clear cause, like alcohol - Associated with obesity, DM, insulin resistance, and metabolic syndrome - Outcomes include hepatic fibrosis, cirrhosis, and hepatocellular carcinoma - DX: Liver biopsy is required for definitive diagnosis - TX: Lifestyle changes can decrease the severity, but there is no medication to treat this - Transplant is the definitive therapy ### Autoimmune Hepatitis - Inflammatory disease that is characterized by autoantibodies and hypergammaglobulinemia - Affects both genders, but favors women - Can range from asymptomatic to fulminant liver failure - ALT and AST may surpass 10-20X normal values - TX: therapy includes prednisone and azathioprine - Remission rate is 60-80% - May require immunosuppression → maintain sterile technique (esp with SAB) - May require transplantation ### Cardiac-related Liver Disease - Can result in - **Ischemic hepatitis** - often results from shock, appears after 2-24h latency - asymptomatic or resembles viral hepatitis - **Congestive hepatopathy** - results from impaired venous outflow secondary to right ventricular failure Cor pulmonale, mitral stenosis, tricuspid regurgitation, constrictive pericarditis, and ischemic cardiomyopathy Typically subclinical, but can have jaundice, malaise, and intermittent RUQ pain ### Miscellaneous - COVID-19: 14-53% have acute liver injury → could be related to cytokine storm - Appears to affect prognosis - **Drug-induced Liver Injury:** can require transplantation - **Acetaminophen** is #1 cause of drug induced liver injury - Symptoms are similar to other liver disease with exception of rash, fever, and eosinophilia - **Wilson Disease:** impaired copper metabolism - Can include psychiatric symptoms - **A1-antitrysin Deficiency:** leads to cirrhosis, but also will cause COPD/emphysema - Only treatment is transplantation - **Hemochromatosis** - excessive systemic iron ### Acute Liver Failure - Critical illness characterized by severe hepatocyte injury that occurs in less than 26 weeks - Massive hepatocyte necrosis ## NA 731 Pathophysiology for Nurse Anesthesia II Fall 2022. Etiology: • Drug-induced: most commonly 2/2 acetaminophen • Viral: most commonly 2/2 Hepatitis A, B, & E • Other causes: HELLP, heat stroke, mushroom ingestion • Presentation includes rapid onset elevation of aminotransferases, altered mental status, and coagulation abnormalities • Early: jaundice, nausea, RUQ pain • Late: encephalopathy, cerebral edema, multiorgan failure • Mgt: treat etiology, supportive care, management of complications ## Cirrhosis - Final stage of chronic liver disease characterized by the pathological replacement of hepatic tissue with scar tissue • S&S: - Early: asymptomatic - Progressive: jaundice, ascites, bruising, encephalopathy, and variceal hemorrhage - Etiology: alcohol-related liver disease, steatohepatitis, HCV, and HBV - DX: - Gold Standard: liver biopsy - Labs: elevated aminotransferases, bilirubin, alk phos, and PT/INR along with thrombocytopenia - TX: transplantation is only curative option ## Ascites - Most common complication of cirrhosis - In decompensated cirrhosis, portal hypertension results in increased blood volume and transudative accumulation of fluid in the peritoneal cavity - S&S: increased abdominal girth, discomfort, weight gain, and dyspnea - TX: low Na diet, diuretics, paracentesis, and albumin replacement ## Varices - Surgical placement of a portosystemic shunt is a possibility - 50% of cirrhosis patients develop varices - Engorged veins in the distal esophagus and/or stomach - Variceal rupture and bleed is an emergent, often fatal outcome with advanced disease - TX: medically managed with nonselective beta-blockers - Will require variceal banding during endoscopy - MAJOR BLEEDING RISK ## Hepatic Encephalopathy - Accumulation of nitrogenous waste (ammonia) due to poor hepatic function leads to neurologic dysfunction that can range from cognitive impairment to coma - Triggers include infection, electrolyte imbalance, and medications like benzodiazepines and antipsychotics • TX: lactulose and rifaximin (antibiotic) - High risk for pneumonia and bacterial peritonitis ## Anesthesia for the Patient with Liver Disease ### Risk Assessment - For acute hepatitis, acute liver failure, and severe chronic hepatitis, the risk of mortality is too high, making elective surgery impossible - With less severe disease, the risk and benefit must be considered - **Severity of disease scores** - **Child-Turcotte-Pugh (CTP)** - point-based system that emphasizes the complications of portal hypertension using total bilirubin, albumin, PT, encephalopathy, and ascites - **Model for End Stage Liver Disease (MELD)** – uses serum bilirubin, INR, creatinine, and sodium to calculate a score - **MELD Score Prediction of 90 Day Mortality** - >40 - 71.3% - 30-39 - 52.6% - 20-29 - 19.6% - 10-19 - 6% - <9 - 1.9% ## NA 731 Pathophysiology for Nurse Anesthesia II Fall 2022 ## Reported Surgery Risk in Patients with Liver Disease | Liver Disease | Type of Surgery | Mortality | Prognostic Factors | |-|-|-|-| | Cirrhosis | Non-laparoscopic biliary surgery | 20% | Ascites, PT, albumin | | | Peptic ulcer disease | 54% | PT, Systolic BP, Hgb | | | Umbilical herniorrhaphy | 13% | Urgency | | | Colectomy | 24% | Encephalopathy, ascites, Hbg | | | Abdominal trauma surgery | 47% | | | | Emergency abdominal surgery | 57% | Child-Pugh class, urgency | | | Lap chole | 1-6% | | | | Emergency cardiac surgery | 80% | Child-Pugh class | | | Elective cardiac surgery | 3-46% | Child-Pugh class | | | Knee replacement | 0% | | | | TURP | 6.7% | | | Chronic hepatitis | Various | 0% | | | Hepatitis C | Lap chole | 0% | | | Acute hepatitis | Ex lap | Up to 100% | Hgb, bilirubin, malignancy | | Obstructive jaundice | Abdominal Surgery | 5-60% | Hgb, bilirubin, malignancy | ## Preoperative Preparation - Risk assessment - All liver disease patients should have CBC, metabolic panel, PT/INR - Preop placement of arterial line to allow BP monitoring and frequent sampling of blood - Placement of a CVP line is controversial and should only be used when necessary (vasopressor) ## Intraoperative Management - Standard monitors - Any anesthetic plan must focus on the maintenance of arterial blood pressure and cardiac output - Both general and regional anesthesia are acceptable, but the specific agents chosen matter the most - General - iso, des, and sevoflurane are acceptable - N2O should be avoided when the expansion of hollow organs is possible - Propofol is safe - Action of benzos will be prolonged - NMBAs are selected based on patient status and procedure needs - Duration of action of steroidal agents may be prolonged - Onset is delayed in cirrhosis patients due to the increased VD (increased TBW) - Opioids should be used judiciously, recall that remifentanil is metabolized even during the anhepatic phase of liver transplantation - RSI may be prudent due to cirrhosis - Regional - be mindful of risk of hemorrhage due to anticoagulation