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Questions and Answers
What is the primary cause of unconjugated hyperbilirubinemia?
What is the primary cause of unconjugated hyperbilirubinemia?
Which condition is characterized by severe jaundice, fever, and vomiting, potentially leading to brain damage if untreated?
Which condition is characterized by severe jaundice, fever, and vomiting, potentially leading to brain damage if untreated?
What is the most common viral agent that necessitates hepatic transplantation in the United States?
What is the most common viral agent that necessitates hepatic transplantation in the United States?
What is the primary indication for liver transplantation worldwide?
What is the primary indication for liver transplantation worldwide?
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What factor may contribute to benign postoperative intrahepatic cholestasis?
What factor may contribute to benign postoperative intrahepatic cholestasis?
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What are the primary determinants for the increase in hepatic blood flow in response to decreased portal flow?
What are the primary determinants for the increase in hepatic blood flow in response to decreased portal flow?
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In the context of liver dysfunction, which condition is associated with a significantly elevated AST:ALT ratio?
In the context of liver dysfunction, which condition is associated with a significantly elevated AST:ALT ratio?
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Which metabolic function of the liver can lead to increased risk of bleeding due to impaired production?
Which metabolic function of the liver can lead to increased risk of bleeding due to impaired production?
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What is a primary risk factor for developing cholelithiasis?
What is a primary risk factor for developing cholelithiasis?
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In the case of choledocholithiasis, what acute complication is frequently recognized that indicates a serious condition?
In the case of choledocholithiasis, what acute complication is frequently recognized that indicates a serious condition?
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Which of the following liver anatomy components is specifically involved in the immediate blood supply to the liver?
Which of the following liver anatomy components is specifically involved in the immediate blood supply to the liver?
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Which factor is least likely to be associated with elevated alkaline phosphatase levels in liver function tests?
Which factor is least likely to be associated with elevated alkaline phosphatase levels in liver function tests?
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Which statement best describes the relationship between hepatic dysfunction and drug metabolism?
Which statement best describes the relationship between hepatic dysfunction and drug metabolism?
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Which laboratory test result pattern is indicative of prehepatic hepatic dysfunction?
Which laboratory test result pattern is indicative of prehepatic hepatic dysfunction?
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Which of the following is NOT a metabolic function of the liver?
Which of the following is NOT a metabolic function of the liver?
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What is a common association found in patients with chronic steatohepatitis?
What is a common association found in patients with chronic steatohepatitis?
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Which of the following statements about autoimmune hepatitis is true?
Which of the following statements about autoimmune hepatitis is true?
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Which of the following conditions is characterized primarily by impaired venous outflow?
Which of the following conditions is characterized primarily by impaired venous outflow?
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What is a significant characteristic of drug-induced liver injury caused by acetaminophen?
What is a significant characteristic of drug-induced liver injury caused by acetaminophen?
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What defines acute liver failure?
What defines acute liver failure?
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Which metabolic disorder is associated with psychiatric symptoms due to impaired copper metabolism?
Which metabolic disorder is associated with psychiatric symptoms due to impaired copper metabolism?
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What is the primary treatment option for A1-antitrypsin deficiency?
What is the primary treatment option for A1-antitrypsin deficiency?
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Which of the following conditions can result in an acute liver injury related to COVID-19?
Which of the following conditions can result in an acute liver injury related to COVID-19?
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What is the primary treatment for variceal bleeding in patients with cirrhosis?
What is the primary treatment for variceal bleeding in patients with cirrhosis?
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Which of the following statements regarding ascites in cirrhosis is correct?
Which of the following statements regarding ascites in cirrhosis is correct?
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Which of the following is NOT considered a common trigger for hepatic encephalopathy?
Which of the following is NOT considered a common trigger for hepatic encephalopathy?
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What is the most reliable method for diagnosing cirrhosis?
What is the most reliable method for diagnosing cirrhosis?
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Which MELD score range indicates a significantly high risk of mortality?
Which MELD score range indicates a significantly high risk of mortality?
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In patients with cirrhosis, which anesthetic agent should be avoided when the expansion of hollow organs is possible?
In patients with cirrhosis, which anesthetic agent should be avoided when the expansion of hollow organs is possible?
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Which surgical procedure in patients with cirrhosis has the highest reported mortality?
Which surgical procedure in patients with cirrhosis has the highest reported mortality?
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What is the expected prevalence of varices developing in patients with cirrhosis?
What is the expected prevalence of varices developing in patients with cirrhosis?
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Which method is generally used for the management of hepatic encephalopathy in patients?
Which method is generally used for the management of hepatic encephalopathy in patients?
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What defines the most significant complication associated with acute hepatitis?
What defines the most significant complication associated with acute hepatitis?
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In liver disease patients, which of the following parameters should be assessed preoperatively?
In liver disease patients, which of the following parameters should be assessed preoperatively?
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Which condition is most commonly associated with drug-induced hepatic failure?
Which condition is most commonly associated with drug-induced hepatic failure?
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What is the characteristic appearance of fluid accumulation in patients with ascites?
What is the characteristic appearance of fluid accumulation in patients with ascites?
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Study Notes
Hepatic Pathophysiology
- Liver dysfunction is common, affecting 4.5 million Americans and causing 40,000 deaths/year in the US.
- Modern therapies have reduced viral infectious hepatic disease, but both alcohol and non-alcohol related liver disease have increased.
- The liver plays a critical role in various metabolic and physiologic processes.
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Metabolic functions:
- Regulates glucose metabolism (gluconeogenesis and glycogenolysis).
- Synthesizes proteins including plasma proteins that bind drugs and proteins like plasma cholinesterase.
- Participates in protein metabolism, bilirubin metabolism, and bile production.
- Clears insulin and metabolizes drugs.
- Hemostasis: The liver synthesizes coagulation factors and proteins crucial for hemostasis.
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Metabolic functions:
Liver Blood Flow
- The liver receives 25% of cardiac output.
- The portal vein and hepatic artery supply blood to the liver.
- Portal vein contributes 75% of blood flow and 50% of the oxygen supply.
- Hepatic artery contributes 25% of blood flow but supplies 50% of the oxygen.
- Blood flow is regulated by intrinsic and extrinsic mediators.
- Liver blood flow is altered in liver disease.
- A reduction in portal vein flow causes an increase in hepatic artery flow.
- A reduction in hepatic artery flow does not affect portal vein flow.
- Elevated portal vein pressure contributes to portosystemic shunt formation and variceal development.
Liver Pathology
- Lobes: The liver is composed of four lobes: right, quadrate, caudate, and left.
- Segments: Each lobe is further divided into segments.
Liver Assessment
- Assessment involves history, physical exam, and laboratory testing.
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History and Physical Exam:
- Risk factors: family history, alcohol use, diabetes, obesity, IV drug use, tattoos, blood transfusions, hepatotoxic drugs.
- Symptoms: fatigue, pruritus, bleeding/bruising, volume overload, weight changes, dark urine.
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Laboratory Data:
-
Liver Chemistry:
- AST:ALT ratio: >2:1 in acute liver dysfunction and 1:1 in nonalcoholic steatohepatitis
- Alkaline Phosphatase, gamma-glutamyltransferase (GGT), and bilirubin levels are useful to determine cholestasis.
- Complete Blood Count (CBC) and Coagulation Studies.
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Liver Chemistry:
Causes of Hepatic Dysfunction Based on Liver Chemistry Tests
- Prehepatic (Increased unconjugated bilirubin): Hemolysis, hematoma resorption, bilirubin overload from transfusions.
- **Intrahepatic (Hepatocellular): (Increased conjugated bilirubin) ** Viral infection, drugs, alcohol, sepsis, hypoxemia, cirrhosis.
- Posthepatic (Cholestatic) (Increased conjugated bilirubin): Biliary stones/tumors, sepsis.
Diseases of the Biliary Tract and Bilirubin
Cholelithiasis
- Gallstones occur when substances in bile harden within the gallbladder.
- Risk factors: obesity, hypercholesterolemia, family history, diabetes, pregnancy, female gender.
- 80% are asymptomatic.
- Common symptoms: pain, nausea, vomiting, indigestion.
- Can lead to right shoulder pain.
- Complications include sepsis.
- Anesthetic Implications:
- Be mindful of the sphincter of Oddi and possible spasms. Consider naloxone, glucagon, or nitrates to address spasms.
- Aspiration risk needs to be considered due to nausea and vomiting.
Choledocholithiasis
- Occurs when a stone obstructs the common bile duct.
- Presents as biliary colic: RUQ pain, intermittent nausea and vomiting.
- Can lead to cholangitis: fever, rigors, and jaundice in addition to biliary colic symptoms.
- Treatment: ERCP with endoscopic sphincterotomy or exploratory laparoscopy/LC with or without IOC.
Hyperbilirubinemia
- Unconjugated (indirect) hyperbilirubinemia: imbalance between bilirubin synthesis and breakdown.
- Conjugated (direct) hyperbilirubinemia: reflex of conjugated bilirubin into the blood due to biliary obstruction.
Gilbert Syndrome
- Inherited disorder leading to unconjugated hyperbilirubinemia.
- Jaundice, fatigue, pain with dehydration, stress, fasting, or exercise.
Crigler-Najjar Syndrome
- Severe, rare inherited disorder causing unconjugated hyperbilirubinemia.
- Can lead to brain damage if untreated.
- Treatment: transfusions and phototherapy.
- Symptoms: severe jaundice, fever, and vomiting.
Benign Postoperative Intrahepatic Cholestasis
- Multifactorial problem associated with hypotension, large blood loss, transfusions, or hypoxemia.
Hepatitis
Viral Hepatitis
- Most commonly caused by Hepatitis A, B, C, D, and E (HXV).
- Each causes acute infection and significant morbidity.
- HBV and HCV are associated with chronic disease states, leading to hepatic transplantation.
| Hepatitis Type | RNA or DNA |
|---|---|
| A | RNA |
| B | DNA |
| C | RNA |
| D | RNA |
| E | RNA |
- New therapies can achieve up to 99% clearance of viral loads for certain HCV subtypes.
- Harvoni: combination drug for HCV treatment.
Alcohol-Related Liver Disease (ALD)
- Leading cause of liver transplantation in the US and globally.
- Patients may be asymptomatic, especially with early-stage or compensated cirrhosis.
- Associated with malnutrition, muscle wasting, and parotid gland hypertrophy.
- Advanced ALD presents with jaundice, ascites, hepatosplenomegaly, and peripheral edema.
- Anesthesia considerations:
- Chronic alcohol abuse: increased MAC requirements and risk of recall.
- Acute intoxication: decreased MAC requirements.
Nonalcoholic Fatty Liver Disease (NAFLD)
- Excessive fat accumulation in the liver without a clear cause like alcohol.
- Associated with obesity, diabetes, insulin resistance, and metabolic syndrome.
- Can progress to fibrosis, cirrhosis, and hepatocellular carcinoma.
- Diagnosis: liver biopsy required for definitive diagnosis.
- Treatment: Lifestyle changes can reduce severity, but no specific medications are available.
- Transplantation is the definitive therapy.
Autoimmune Hepatitis
- Inflammatory disease characterized by autoantibodies and hypergammaglobulinemia.
- Affects both genders, but more common in women.
- Can range from asymptomatic to fulminant liver failure.
- ALT and AST levels may be significantly elevated (10-20 times normal).
- Treatment: Prednisone and azathioprine.
- Remission rate: 60-80%.
- May require immunosuppression: maintain sterile technique, especially with spinal anesthesia.
- Transplantation may be required.
Cardiac-Related Liver Disease
- Can manifest as ischemic hepatitis or congestive hepatopathy.
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Ischemic Hepatitis: Often occurs after shock, with 2-24 hours latency.
- Asymptomatic or similar to viral hepatitis.
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Congestive Hepatopathy: Impaired venous outflow due to right ventricular failure.
- Usually subclinical, but may cause jaundice, malaise, and intermittent RUQ pain.
Miscellaneous Liver Diseases
-
COVID-19: Can cause acute liver injury in 14-53% of cases.
- May be related to cytokine storm.
- Affects prognosis.
-
Drug-induced liver injury: Can require transplantation.
- Acetaminophen is the most common cause.
- Symptoms are similar to other liver diseases, except for skin rash, fever, and eosinophilia.
-
Wilson Disease: Impaired copper metabolism.
- Can include psychiatric symptoms.
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Alpha-1 Antitrypsin Deficiency: Leads to cirrhosis and COPD or emphysema.
- Treatment: Transplantation.
- Hemochromatosis: Excessive systemic iron.
Acute Liver Failure
- Critical illness with severe hepatocyte injury within 26 weeks.
- Massive hepatocyte necrosis.
- Causes: drug-induced (acetaminophen), viral (Hepatitis A, B, E), HELLP, heat stroke, mushroom ingestion.
- Symptoms progress from early stage to late stage.
- Early: jaundice, nausea, RUQ pain.
- Late: encephalopathy, cerebral edema, multiorgan failure.
- Management: Treat underlying cause, supportive care, manage complications.
Cirrhosis
- The final stage of chronic liver disease.
- Characterized by the replacement of hepatic tissue with scar tissue.
- Symptoms progress from early to late stages.
- Early: Asymptomatic.
- Progressive: jaundice, ascites, bruising, encephalopathy, variceal hemorrhage.
- Causes: ALD, NAFLD, HCV, HBV.
- Diagnosis: Liver biopsy (gold standard), elevated aminotransferases, bilirubin, alkaline phosphatase, PT/INR, thrombocytopenia.
- Treatment: Transplantation is the only curative option.
Ascites
- Common complication of cirrhosis.
- Increased blood volume and transudative fluid accumulation in the peritoneal cavity due to portal hypertension in decompensated cirrhosis.
- Symptoms: increased abdominal girth, discomfort, weight gain, dyspnea.
- Treatment: low sodium diet, diuretics, paracentesis, albumin replacement.
Varices
- Engorged veins in the distal esophagus and/or stomach.
- Occur in 50% of cirrhosis patients.
- Variceal rupture and bleeding is an emergent, life-threatening complication.
- Treatment: nonselective beta-blockers, variceal banding.
- High bleeding risk.
Hepatic Encephalopathy
- Neurologic dysfunction due to ammonia accumulation in the blood caused by impaired hepatic function.
- Ranges from cognitive impairment to coma.
- Triggers: infection, electrolyte imbalance, medications (benzodiazepines, antipsychotics).
- Treatment: lactulose, rifaximin.
- High risk for pneumonia and bacterial peritonitis.
Anesthesia for the Patient with Liver Disease
Risk Assessment
- Elective surgery is not recommended in cases of acute hepatitis, acute liver failure, or severe chronic hepatitis due to high mortality risk.
- Risk and benefit must be considered for patients with less severe liver disease.
- Severity of disease scores: Child-Turcotte-Pugh (CTP) and Model for End-Stage Liver Disease (MELD) scores are used to assess risk and predict mortality.
Child-Turcotte-Pugh Score
- Point-based system that evaluates complications of portal hypertension using:
- Total bilirubin
- Albumin
- Prothrombin time (PT)
- Encephalopathy
- Ascites
Model for End-Stage Liver Disease (MELD) Score
- Uses:
- Serum bilirubin
- INR
- Creatinine
- Sodium
MELD Score and Mortality
-
40: 71.3% mortality within 90 days
- 30-39: 52.6% mortality within 90 days
- 20-29: 19.6% mortality within 90 days
- 10-19: 6% mortality within 90 days
- < 9: 1.9% mortality within 90 days
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, Hemoglobin (Hgb) | |
| Umbilical herniorrhaphy | 13% | Urgency | |
| Colectomy | 24% | Encephalopathy, ascites, Hgb | |
| Abdominal trauma surgery | 47% | ||
| Emergency abdominal surgery | 57% | Child-Pugh class, urgency | |
| Laparoscopic cholecystectomy (lap chole) | 1-6% | N/A | |
| Emergency cardiac surgery | 80% | Child-Pugh class | |
| Elective cardiac surgery | 3-46% | Child-Pugh class | |
| Knee replacement | 0% | N/A | |
| Transurethral resection of the prostate (TURP) | 6.7% | N/A | |
| Chronic hepatitis | Various | 0% | N/A |
| Hepatitis C | Lap chole | 0% | N/A |
| Acute hepatitis | Exploratory laparotomy (Ex lap) | Up to 100% | Hgb, bilirubin, malignancy |
| Obstructive jaundice | Abdominal surgery | 5-60% | Hgb, bilirubin, malignancy |
Preoperative Preparation
- Risk assessment is crucial.
- All patients with liver disease should have CBC, metabolic panel, and PT/INR.
- Consider pre-operative placement of an arterial line to monitor blood pressure and allow for frequent blood sampling.
- CVP line placement is controversial - only use when medically necessary.
Intraoperative Management
- Monitor standard vitals.
- Maintain arterial blood pressure and cardiac output.
- Both general and regional anesthesia are acceptable, but anesthetic agents should be carefully selected.
General Anesthesia
- Isoflurane, desflurane, and sevoflurane are acceptable.
- Avoid nitrous oxide if possible.
- Propofol is safe.
- Benzodiazepine duration of action may be prolonged.
- Neuromuscular blocking agents (NMBAs) should be selected based on patient status and procedure needs.
- Steroidal NMBAs may have a prolonged duration of action.
- Onset of NMBAs may be delayed in cirrhosis patients due to increased volume of distribution (VD) and total body water (TBW).
- Use opioids judiciously. Remifentanil is metabolized even during the anhepatic phase of liver transplantation.
- Rapid sequence induction (RSI) may be prudent due to cirrhosis.
Regional Anesthesia
- Be mindful of the risk of hemorrhage due to anticoagulation.
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Test your knowledge on various liver diseases and conditions in this quiz. Explore topics such as hyperbilirubinemia, liver transplantation, and the consequences of liver dysfunction. Perfect for medical students and professionals interested in hepatology.
