NA 731 Hepatic Pathophysiology Fall 2022 PDF

# NA 731 Pathophysiology for Nurse Anesthesia II Fall 2022 ## Hepatic Pathophysiology ### Epidemiology - 4.5 million 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 nonalc...

# NA 731 Pathophysiology for Nurse Anesthesia II Fall 2022 ## Hepatic Pathophysiology ### Epidemiology - 4.5 million 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 #### 1. Metabolic Functions - CHO metabolism: moderates gluconeogenesis and glycogenolysis - Protein synthesis: including plasma proteins that bind drugs 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 duration of action - Protein metabolism - Bilirubin metabolism: bilirubin is conjugated so it can be incorporated into bile - Bile production: produced by each lobule continuously, stored in the gallbladder, released in response to cholecystokinin (CCK) which is required for metabolism of fat-soluble vitamins and minerals (A, D, E, & K) - increased risk for bleeding secondary to decreased amounts of vitamin K dependent factors - Insulin clearance: 50% removed with the first portal pass - Drug metabolism: Phase 1 and Phase 2 reactions, cytochrome P450 system is crucial #### 2. 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 superior mesenteric vein (SMV), 75% of flow, with 50% of oxygen supply - Hepatic artery: only 25% of blood flow, but supplies 50% of oxygen - Regulated by intrinsic and extrinsic mediators - If portal flow decreases, hepatic artery flow increases but only in 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 - Each of these can be surgically removed - Eight total, indicated on image to the right - Gallbladder is posterior to segments 5 and 8 ### Liver Assessment - History/Physical: risk factors for liver disease, severity of findings, and comorbidities - Risk factors: family history, alcohol use, diabetes mellitus, obesity, intravenous drug use, tattoos, transfusions, hepatotoxic drugs - Assess for: fatigue, pruritus, bleeding/bruising, volume overload, weight change (especially 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 has an AST:ALT ratio of at least 2:1, whereas nonalcoholic steatohepatitis has an AST:ALT ratio of 1:1 - Alkaline Phosphatase, gamma-glutamyltransferase (GGT), and bilirubin are useful to determine cholestasis - Complete blood count & coagulation studies - Assess synthetic function: - Complete blood count: focus on formed blood elements (red blood cells, hemoglobin, hematocrit) - International normalized ratio (INR): Less than 1.5 for regional - Imaging: ultrasound (U/S), computed tomography (CT), magnetic resonance imaging (MRI) ### Causes of Hepatic Dysfunction Based on Liver Chemistry Test | Hepatic Dysfunction | Bilirubin | Aminotransferase 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 Tones/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 the gallbladder - Risk factors: obesity, hypercholesterolemia, family history, diabetes, pregnancy, female gender - 80% are asymptomatic, common symptoms are pain, nausea, vomiting, and indigestion - Right shoulder referred pain - Can develop sepsis - Anesthetic implications: - Consider the use of opioids within the context of the sphincter of Oddi: can antagonize a spasm with naloxone, glucagon, or a nitrate - 0.25 mg glucagon: increases cyclic adenosine monophosphate (cAMP) and inotropy (this would be undesirable for hypertrophic obstructive cardiomyopathy patients) - It is likely a laparoscopic case - Consider aspiration risk secondary to nausea and vomiting #### Choledocholithiasis - Complication of cholelithiasis where a stone blocks the common bile duct - Presentation is often as biliary colic: pain in the right upper quadrant with intermittent nausea and vomiting - Can lead to cholangitis: associated with fever, rigors, and jaundice in addition to previously identified symptoms - Treatment: - Endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy - Exploratory laparoscopy/laparotomy, with or without intraoperative cholangiography #### Hyperbilirubinemia - **Unconjugated (indirect) Hyperbilirubinemia:** result from imbalance between the synthesis and breakdown of bilirubin - **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-Najjar Syndrome - Severe, very rare inherited disorder that can result in brain damage if untreated - Treatment: transfusions and phototherapy - Signs and Symptoms: 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 - Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are associated with chronic disease states, both of which commonly result in a need for hepatic transplantation ### Hepatic Transplantation - HCV is the most common viral agent that leads to hepatic transplantation in the US. - New therapies result in a clearance of up to 99% of viral loads for 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 are often asymptomatic with alcohol-related liver disease (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 anesthesia. What are your concerns now? ### Steatohepatitis - Chronic: greatly increases minimum alveolar concentration (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, such as alcohol - Associated with obesity, diabetes mellitus, insulin resistance, and metabolic syndrome - Outcomes include: hepatic fibrosis, cirrhosis, and hepatocellular carcinoma - Diagnosis: Liver biopsy is required for definitive diagnosis - Treatment: Lifestyle changes can decrease the severity, but there is no medication to treat this. Liver 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 - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) may surpass 10-20 times normal values - Treatment: - Prednisone - Azathioprine - Remission rate is 60-80% - May require immunosuppression: maintain sterile technique (especially with spinal anesthesia) - May require transplantation ### Cardiac-related Liver Disease - Can result in: - Ischemic hepatitis: often results from shock, appears after 2-24 hourslatency - 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 right upper quadrant pain ### Miscellaneous - COVID-19: 14-53% have acute liver injury, possibly related to a cytokine storm - Appears to affect prognosis - Drug-induced Liver Injury: can require transplantation - Acetaminophen is the #1 cause of drug-induced liver injury - Symptoms are similar to other liver disease, with the exception of rash, fever, and eosinophilia - Wilson Disease: impaired copper metabolism - Can include psychiatric symptoms - A1-antitrypsin Deficiency: leads to cirrhosis, but will also cause chronic obstructive pulmonary disease/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 due to acetaminophen - Viral: most commonly due to Hepatitis A, B, and E - Other causes: HELLP syndrome, heat stroke, mushroom ingestion - Presentation includes rapid onset elevation of aminotransferases, altered mental status, and coagulation abnormalities - Early: jaundice, nausea, right upper quadrant pain - Late: encephalopathy, cerebral edema, multiorgan failure - Management: treat etiology, supportive care; manage complications ### Cirrhosis - Final stage of chronic liver disease characterized by the pathological replacement of hepatic tissue with scar tissue. - Signs and Symptoms: - Early: asymptomatic. - Progressive: jaundice, ascites, bruising, encephalopathy, and variceal hemorrhage - Etiology: Alcohol-related liver disease, Nonalcoholic fatty liver disease, Hepatitis C Virus, and Hepatitis B Virus - Diagnosis: - Gold Standard: liver biopsy. - Laboratory values: elevated aminotransferases, bilirubin, alkaline phosphatase, and international normalized ratio/prothrombin time with thrombocytopenia. - Treatment: Transplantation is the only curative option. ### Ascites - Most common complication of cirrhosis. - In decompensated cirrhosis, portal hypertension results in an increased blood volume and transudative accumulation of fluid in the peritoneal cavity. - Signs and Symptoms: increased abdominal girth, discomfort, weight gain, and dyspnea - Treatment: low sodium diet, diuretics, paracentesis, and albumin replacement. - Surgical placement of a portosystemic shunt is a possibility ### Varices - 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 - Treatment: - Medically managed with nonselective beta-blockers - 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 - Treatment: 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. - Child-Turcotte-Pugh (CTP): point-based system that emphasizes the complications of portal hypertension using total bilirubin, albumin, prothrombin time, encephalopathy, and ascites. - Model for End Stage Liver Disease (MELD): uses serum bilirubin, international normalized ratio, creatinine, and sodium to calculate a score. **Table: MELD Scores compared to 90 Day Mortality** | MELD Score | 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 **Table: Reported Surgery Risk in Patients with Liver Disease** | Liver Disease | Type of Surgery | Mortality | Prognostic Factors | |---|---|---|---| | Cirrhosis | Non-laparoscopic biliary surgery | 20% | Ascites, prothrombin time, albumin | | Cirrhosis | Peptic ulcer disease | 54% | Prothrombin time, systolic blood pressure, hemoglobin| | Cirrhosis | Umbilical herniorrhaphy| 13%| Urgency| | Cirrhosis | Colectomy | 24% | Encephalopathy. ascites, hemoglobin| | Cirrhosis | Abdominal trauma surgery | 47% | | | Cirrhosis | Emergency abdominal surgery | 57% | Child-Pugh class, urgency | | Cirrhosis | Lap chole | 1-6% | | | Cirrhosis | Emergency cardiac surgery | 80% | Child-Pugh class | | Cirrhosis | Elective cardiac surgery | 3-46% | Child-Pugh class | | Cirrhosis| Knee replacement | 0% | | | Cirrhosis| Transurethral Resection of the Prostate (TURP)| 6.7% | | | Chronic Hepatitis | Various | 0% | | | Hepatitis C | Lap chole | 0% | | | Acute Hepatitis | Ex lap | Up to 100% | | | Obstructive Jaundice | Abdominal Surgery | 5-60% | Hemoglobin, bilirubin, malignancy| ### Preoperative Preparation - Risk Assessment: - All liver disease patients should have a complete blood count, metabolic panel, and prothrombin time/international normalized ratio. - Preoperative placement of an arterial line to allow blood pressure monitoring and frequent sampling of blood. - Preoperative placement of a central venous pressure 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: isoflurane, desflurane, and sevoflurane are acceptable - Nitrous oxide should be avoided when the expansion of hollow organs is possible - Propofol is safe - Action of benzodiazepines will be prolonged: - Duration of action of steroidal agents may be prolonged. - Onset is delayed in cirrhosis patients due to increased volume of distribution (increased total body water). - Opioids should be used judiciously; recall that remifentanil is metabolized even during the anhepatic phase of liver transplantation. - Rapid sequence intubation may be prudent due to cirrhosis. - Regional: Be mindful of risk of hemorrhage due to anticoagulation. 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