Hepatobiliary Flashcards
What Laboratory Tests Are Helpful in Screening for Undiagnosed Liver Disease Preoperatively?
○ Bilirubin is a product of the normal catabolism of heme during the clearance of senescent or abnormal red blood cells.
○ Albumin-bound bilirubin (unconjugated bilirubin sometimes termed indirect-reacting) is transported to the liver, conjugated by the liver, and rapidly excreted into bile.
○ The excretion process in a healthy individual is very efficient so that normally <10% of measured total bilirubin in the plasma will be in the conjugated (sometimes termed direct-reacting) form.
In liver disease, conjugated bilirubin will be elevated and unconjugated bilirubin may be elevated or normal.
○ In hemolysis, conjugated bilirubin will be normal and unconjugated will be elevated.
○ In Gilberts syndrome, conjugated bilirubin will normal and unconjugated bilirubin will be elevated.
- Gilberts syndrome in an inherited disorder of disrupted ability to conjugate bilirubin. It is a relatively benign condition.
- Gilberts syndrome is found in about 5% of the population.
○ Jaundice is not uncommon particularly at times of stress or during an illness.
- A sub-set of Gilberts syndrome patients are at increased risk of paracetamol toxicity.
- The commonly measured enzymes are alanine amino-transferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP).
○ ALT is present primarily in the liver and is a more specific marker of liver injury than AST which can be elevated in the absence of hepatic damage.
○ Isolated AST elevations may be reflection of cardiac/skeletal muscle damage, kidney, brain, or lung injury.
○ ALP is found in all tissues but especially in the liver and bone.
○ ALP may be elevated in hepatic-related disease including biliary obstruction and hepatitis and in bone-related pathology including osteoporosis, osteoblastic bone lesions, and osteomalacia.
○ If the AST and ALT are higher of than the ALP, this is typical of hepatocellular injury.
○ If the ALP is higher than the AST and ALT, this is typical of cholestatic disease.
○ If the ALP is elevated and the AST and ALT are near normal, this is typical of cholestatic/infiltrative liver disease.
○ Further reading on this subject is available in an excellent guide to liver test interpretation [1].
○ Tests of liver function include albumin and prothrombin time (PT).
○ In the setting of preoperative assessment, a history indicative of the potential for liver injury and/or symptoms should prompt a requisition for liver enzymes and indices of liver function.
○ Mild elevations of ALT and AST (<5X upper limit of normal) in the absence of symptoms of liver dysfunction are common, being present in up to 10% of the adult population of the United States [2]. Most are caused by non-alcoholic fatty liver (a non-aggressive subtype of non-alcoholic fatty
liver disease [NAFLD]) and chronic alcohol intake. These transaminase elevations are not a reason to postpone an elective surgical procedure.
What Commonly Used Drugs Can Be Associated with Elevated Liver Transaminases?
○ Clincally significant drug-induced liver injury is uncommon.
○ Many commonly used drugs, including acetaminophen in therapeutic doses, can cause elevated transaminases.
○ Other medications that can have a similar effect on hepatic transaminases include lisinopril, losartan, ciprofloxacin, methotrexate, allopurinol, NSAIDs, bupropion, risperidone, SSRIs, and herbal medications.
What Is Cirrhosis?
○ Chronic liver inflammation leads to replacement of functioning hepatocytes with fibrotic tissue, the latter leading to portal hypertension and eventually the development of collateral portosystemic shunts in the form of varices.
○ The progression and consequences of the chronic liver inflammation are highly variable among individuals
○ Cirrhosis is the late stage of this process and is diagnosed definitively by
liver biopsy
What Are the Common Causes of Cirrhosis?
○ North America and Europe, by far the most common causes of cirrhosis are alcoholic liver disease, chronic viral hepatitis, and non-alcoholic steatohepatitis (NASH), the aggressive subtype of NAFLD.
○ Less common causes include drug-induced liver damage, autoimmune hepatitis, primary and secondary biliary cirrhosis, and right-sided heart failure
How Important Is It to Identify the Cirrhotic
Patient Prior to Elective Surgery?
Cirrhosis markedly increases the risk of elective surgery. In a
review of over 400,000 open aortic valvular procedures
included in the U.S. National Inpatient Sample Healthcare
Cost Utilization Project database, Steffen et al. [4] found in a
propensity matched analysis that the presence of cirrhosis
more than tripled the mortality rate, doubled the rate of acute
renal failure postoperatively, and prolonged the risk-adjusted length of stay. A similar effect has been observed in much
less invasive procedures. Querying the American College of
Surgeons National Surgical Quality Improvement database
of over 21,000 patients undergoing surgery for degenerative
disease of the spine between 2006 and 2015, Goel et al. [5]
found that, based on preoperative laboratory values, mild and
severe liver disease was present in 2.2% and 1.6% of patients,
respectively. The 30-day mortality rates in those with mild
and severe liver disease was 1.7% and 5.1%, respectively,
whereas it was 0.6% in those without liver disease.
Are There Any Simple Non-invasive Scoring Systems to Assist in Reaching a Probable Diagnosis of Cirrhosis?
The modified Bonacini cirrhosis discriminant score (BDS) is calculated using the platelet count, the ALT:AST ratio, and INR. A higher score makes cirrhosis more likely (Table 22.1) [6].r
How Is the Severity of Cirrhosis Estimated?
A validated tool in estimating cirrhosis severity in chronic
liver disease is the Child-Turcotte-Pugh (CTP) score. The
Model for End-Stage Liver Disease (MELD) score stratifies
severity of end-stage liver disease for transplant planning
(Table 22.2) [7] .
Can Perioperative Mortality Risk in Cirrhotic Patients Be Predicted?
○ The data derived from the CTP and MELD scores are helpful in risk estimation but may overestimate risk for individual surgical procedures such as umbilical hernia repair.
○ In general, it appears that the laparoscopic approach is preferable in cirrhotic patients if feasible.
○ Patients at very high risk (CTP Class C; MELD >20) are often on a liver transplant list, and elective surgery should be postponed if possible, pending this intervention.
○ The latest clinical practice update from the American Society of
Gastroenterology emphasizes the paucity of data available to support definitive individual surgical risk stratification in patients with cirrhosis and stresses the importance of referral to, and management by, teams skilled in treating patients with advanced liver disease
What Was the Etiology of Liver Dysfunction in This Case?
- Congestive hepatopathy is a relatively uncommon complication of right heart failure and occurs because of decreased liver blood flow, arterial oxygen desaturation, and increased hepatic venous pressures.
- Tricuspid valve dysfunction/damage is increasingly being recognized as a serious complication of pacemaker or AICD lead insertion into the right ventricle [10].
- Management options include lead extraction and/or valve repair or replacement
- Elevated liver transaminases are indicative of
(a) Subsequent surgical morbidity
(b) Hepatocellular injury if AST elevation is
predominant
(c) Cholestatic injury if ALP elevation is predominant
(d) Recent alcohol intake
(e) Poor liver function
- Cirrhosis
(a) Is a consequence of chronic liver inflammation
(b) Involves replacement of liver cells with fat cells
(c) Is easy to diagnose
(d) If present, increases the risk of elective surgery
(e) Is associated with renal failure
2a. T 2b. F 2c. F 2d. T 2e. T
What Are the Common Reasons for Transplantation?
○ Hepatocellular carcinoma and hepatitis C virus cirrhosis are the most common diseases leading to liver transplantation, followed by patients with alcoholic cirrhosis and non-alcoholic steatohepatitis
○ Other causes of cirrhosis that may require transplantation include hepatitis B, hemochromatosis, Wilson disease, and autoimmune hepatitis.
○ Diseases of the bile ducts—primary biliary cirrhosis, primary sclerosing cholangitis, and biliary atresia (in children)—are also conditions that can lead to transplantation.
○ Acute liver failure is an indication in less than 10% of liver transplants.
- This is a decline in liver function with encephalopathy within 26 weeks of jaundice in a patient with no prior liver disease.
- Etiologies are mostly viral (hepatitis A, B) or drug-induced (acetaminophen overdose)
What Is a MELD Score?
○ With the diverse range of causes of liver diseases, a way to prioritize patients for transplantation was developed based on laboratory data.
○ Model for End-stage Liver Disease (MELD) is a prognostic model that in its original form was a scoring system to predict 3-month mortality in patients with chronic liver disease undergoing transjugular intrahepatic
portosystemic shunt (TIPS).
○ Variables used to calculate the original MELD score were serum bilirubin, serum creatinine, INR, and cause of the liver disease.
○ It was later modified (MELD-Na) to include serum sodium; the etiology
contribution was dropped.
○ Serum sodium is a predictor of mortality in end-stage liver disease. MELD-Na is used to allocate donor organs to the sickest patient.
○ In patient populations where there is no, or little liver cirrhosis,
MELD-Na will not predict the un-transplanted mortality rate.
-These conditions—called MELD exceptions—are awarded additional points.
- They include hepatocellular carcinoma, portopulmonary hypertension, hepatopulmonary syndrome, and hepatic artery thrombosis within 14 days of hepatic surgery.
Is This Patient’s Hyponatremia a Concern?
○ About 20% of prospective liver transplant patients are hyponatremic (serum sodium ≤130 mmol/L) [9].
○ A number of factors contribute to hyponatremia, the most prominent
being the systemic vasodilation of ESLD and subsequent release of antidiuretic hormone, resulting in excessive renal water retention relative to sodium.
○ Some medications (e.g., beta-blockade used for the treatment of variceal hemorrhage and some anti-hypertensive medications) are also contributing factors.
○ Serum sodium as a predictor of mortality in the pre-transplantation population is well established.
○ It is also a concern during the intra- and postoperative setting.
○ Patients with severe hyponatremia (<125 mmol/l) have a longer ICU
stay compared to those with normal levels [11].
○ Rapid shifts (>10 mmol/l rise in 24 h) in serum sodium are associated
with worse outcomes, including neurological deficits and increased 6-month mortality [12].
- Central pontine myelinolysis is an obvious concern, but increased risk of infectious complications, transfusion, and renal impairment have also
been demonstrated.
○ Intraoperative sodium <130 mmol/L is independently associated with a significantly higher 1-year mortality.
○ Liver transplantation can involve significant blood loss with massive transfusion, hemodynamic derangements, fluid shifts, and administration
of large volumes of colloid and crystalloid solutions.
○ For the anesthesia practitioner, preventing rapid intraoperative sodium changes can be challenging.
○ Having a normal or close-to-normal serum sodium at the time of transplantation is an advantage.
What Can Be Done to Correct the Hyponatremia?
○ There are two windows of opportunity available to the practitioner where correction can be attempted—in the few weeks or months prior to transplantation, and also in the few hours available after hospital admission when an organ becomes available.
○ In the outpatient setting, the aim is to remove contributory factors where possible, e.g., beta-blockers, antihypertensive medication.
○ Water restriction (1–1.5 L/day) should be considered [10].
○ Hypokalemia should be addressed, as potassium will raise the serum sodium concentration when corrected
○ Vasopressin receptor antagonists produce a solute-free increase in urine production.
○ Thirst is a major side effect that can limit the serum sodium rise. Where the ESLD vasodilatation causes hypotension, midodrine (an alpha-1-antagonist) can be used to maintain blood pressure and reduce water retention [17].
○ In the hospital setting, there may be sufficient time following admission for a slow controlled correction of low sodium levels prior to transplantation. Strategies include use of hypertonic saline, albumin infusion, and hemodialysis if there is significant renal impairment.
○ Expert advice should be sought, as these actions if improperly executed can cause more harm than good, i.e., when a rapid rise in sodium level
occurs [18]
