Hepatic part 2 Flashcards
Excess bilirubin in the ECF is known as
jaundice
large quantities of unconjugated or conjugated bilirubin
Common causes of jaundice include:
increased destruction of RBCs- hemolytic jaundice
obstruction of bile ducts or damage to hepatocytes preventing bilirubin from being excreted- obstructive jaundice
The toxic form of bilirubin to hepatocytes is
conjugated form
In hemolytic jaundice, RBS are
hemolyzed rapidly
- also have increased production of bilirubin by macrophages
- increased unconjugated bilirubin- hepatocytes cannot process all of the bilirubin
When RBCs are hemolyzed rapidly in hemolytic jaundice, it results in an
increase in unconjugated bilirubin in the blood
-but also a secondary increase in conjugated (direct) bilirubin
In hemolytic jaundice, the excretory function of the liver
is not impaired
In hemolytic jaundice, the rate of formation of urobilinogen
in the intestines increases and urinary excretion increases
Obstructive jaundice can be due to
obstruction of the common bile duct (most common)
damage to hepatic cells
Obstruction of the common bile duct in obstructive jaundice can be due to
gallstone & malignancy
Damage to hepatic cells in obstructive jaundice can be a result of
hepatitis
Describe the formation of bilirubin in obstructive jaundice.
Unconjugated bilirubin enters the hepatocytes and is conjugated in the usual way
- the rate of conjugated bilirubin formation is normal but it cannot pass from the liver into the intestines
- the conjugated bilirubin enters the blood probably by rupture of the bile Canaliculi and direct emptying of bile into the lymph system
In obstructive jaundice, most of the bilirubin in the plasma exists in
the conjugated form
Describe the diagnostic differences between hemolytic & obstructive jaundice.
hemolytic jaundice- almost all bilirubin in the plasma is the unconjugated form (AKA free bilirubin)
obstructive jaundice- bilirubin in the plasma is in the conjugated form
In obstructive jaundice, when there is total obstruction of bile flow,
no conjugated bilirubin can reach the intestines to be converted to urobilinogen
no urobilinogen is reabsorbed into the blood and excreted by the kidney- test for urobilinogen in the urine is completely negative
Generally liver function tests are not
very sensitive or specific
Serum transaminase measurements reflect
hepatocellular integrity as apposed to liver function
Tests that measure the livers synthetic function include:
serum albumin
prothrombin time or INR
cholesterol
& pseudocholinesterase
Due to its large functional reserve, lab tests may be
NORMAL in the presence of cirhossis
In order to assess overall liver function,
we must take tests in total as no one tests reflects overall liver function
Liver abnormalities are typically divided into
parenchymal disorders (hepatocellular dysfunction) obstructive disorders (biliary excretion)
Normal total bilirubin is encompassing of
conjugated + unconjugated
is < 1.5 mg/dL
reflects the balance between production and biliary excretion
Jaundice is usually clinically evident when the total bilirubin is
> 3.0 mg/dL
A predominantly conjugated hyperbilirubinemia is associated with
an increased urobilinogen & may reflect: intrahepatic cholestasis, extrahepatic biliary obstruction
both of these may lead to hepatocellular dysfunction
_________ is toxic to cells
conjugated bilirubin; unconjugated is not
A primary unconjugated hyperbilirubinemia may be seen with
hemolysis, congenital, or acquired defects in bilirubin conjugation
Serum aminotransferases are enzymes released in the circulation as a result of
hepatocellular injury
Two commonly measured serum aminotransferases include
aspartate aminotransferase (AST) Alanine aminotransferase (ALT)
Aspartate aminotransferase is present in
many tissues in addition to the liver (non-specific)
heart, skeletal muscle, & kidneys
Alanine aminotransferase is present in
the liver (more specific than AST)
Normal AST & ALT levels are
below 35 to 45 IU/L
Mild elevations in AST & ALT are seen with
cholestasis or metastatic disease
Absolute levels of AST & ALT are
of value in acute liver disease- drug OD, ischemic injury, fulminant hepatitis
poorly correlate with the degree of hepatic injury in chronic liver disease
Serum alkaline phosphatase is produced in
the liver bone, small bowel, kidneys, and placenta and is excreted into the bile
Most of the circulating alkaline phosphate comes from
bone
In the presence of biliary obstruction, alkaline phosphate
(More of it) is synthesized and released into the circulation
Elevations up to 2x normal of serum alkaline phosphatase are associated with
hepatocellular injury or hepatic metastatic disease
Higher elevations of serum alkaline phosphatase are indicative of
intrahepatic cholestasis & biliary obstruction
Serum albumin half life is
long and therefore its value may initially be normal with acute liver disease
Serum albumin values <2.5 are generally indicative of
chronic liver disease, acute stress, & malnutrition
Hypoalbuminemia can also occur due to increase loss of albumin via the
GI tract (enteropathy with protein loss) in the urine (nephrotic syndrome)
Increased ammonia in the blood usually reflects
disruption of hepatic urea synthesis
Marked elevations of blood ammonia usually reflect
severe hepatocellular damage
A PT of > 3 to 4 seconds from control
is considered significant & corresponds to an INR of 1.5
PT measures the activity of
fibrinogen, Factor II (prothrombin), factor V, factor VII, & factor X
Factor VII has a _____ half-life therefore
short half-life; the PT is useful in evaluating hepatic synthetic function of patients with acute or chronic liver disease
A prolonged PT usually reflects
severe liver disease because only 20-30% of normal factor activity is necessary for NL conjugation
If the PT does not correct following IV administration of Vitamin K, then
severe liver disease is likely present (correct requires 24 hours)
Hepatic blood flow is usually (w/ anesthetics)
decreased during general & regional anesthesia due to direct and indirect effects of:
anesthetic agents themselves, type of ventilation, & surgical procedure
Describe the diagnostic features (include bilirubin, aminotransferase enzymes, alkaline phosphatase, prothrombin time, & albumin) for pre-hepatic liver dysfunction.
Bilirubin- increased (unconjugated fraction) aminotransferase enzymes- no change alkaline phosphatase- no change prothrombin time- no change albumin- no change
Causes of pre-hepatic liver dysfunction include:
hemolysis, hematoma, reabsorption, bilirubin overload from whole blood
Describe the diagnostic features (include bilirubin, aminotransferase enzymes, alkaline phosphatase, prothrombin time, & albumin) for intrahepatic (parenchymal/hepatocellular) liver dysfunction.
Bilirubin- increased (conjugated fraction)
aminotransferase- markedly increased
alkaline phosphatase- no change to slightly increased
prothrombin time- prolonged
albumin- decreased
Causes of intrahepatic liver dysfunction include:
viruses, drugs, sepsis, arterial hypoxemia, CHF, & cirrhosis
Describe the diagnostic features (include bilirubin, aminotransferase enzymes, alkaline phosphatase, prothrombin time, & albumin) for post-hepatic (cholestasis) liver dysfunction
Bilirubin- increased (conjugated fraction)
aminotransferase- normal to slightly increased
alkaline phosphatase- markedly increased
prothrombin time- no change to prolonged
albumin- no change to decreased
Causes of post-hepatic liver dysfunction include:
stones, cancer, & sepsis
Describe the effect that volatile agents has on portal blood flow.
all volatile agents decrease portal blood flow
greatest with halothane/ least with isoflurane
Spinal & epidural anesthesia decrease hepatic blood flow primarily by
decreasing blood pressure
General anesthesia usually decreases hepatic blood flow by
decreasing blood pressure & CO & resulting SNS stimulation
All anesthetic agents cause
indirectly decreased hepatic blood flow in proportion to any decrease in CO or MAP
-decrease in CO also reduces hepatic blood flow by reflex SNS stimulation and vasoconstriction of the arterial and venous sphlanchnic vasculature
Describe the ventilatory effects on hepatic blood flow.
controlled PPV with high mean airway pressures decrease venous return & CO & compromise hepatic blood flow
PEEP accentuates these effects
The most advantageous ventilation for maintaining hepatic blood flow is
spontaneous ventilation
Hypoxemia will produce (in relation to hepatic blood flow)
increase SNS stimulation & decrease hepatic blood flow.
Hypo & hypercapnea/acidosis & alkalosis have
variable effects on hepatic blood flow
Drugs that decrease hepatic blood flow include
beta adrenergic blockers
alpha 1 adrenergic agonist
& vasopression
This drug is though to increase hepatic blood flow:
low dose dopamine
Surgical procedures on or near the liver can reduce hepatic blood flow most likely by:
SNS activation, local vascular reflexes, direct compression of vessels of hepatic circulation
The endocrine stress response may be at least partially blunted by
regional anesthesia, deep general anesthesia, & pharmacological block of the SNS (esmolol & labetalol)
Endocrine stress response secondary to fasting and surgical stress results in increased circulating levels of
catecholamines, glucagon, & cortisol
Carbohydrates & protein stores are mobilized resulting in
hyperglycemia & negative nitrogen balance
In terms of biliary tract function, all opioids can potentially cause
spasm of the sphincter of Oddi and increase biliary pressure
The order of effect of opioids that cause spasm is
fentanyl/alfentanil (short-lived), morphine, meperidine, butorphanol, nalbuphine
IV opioids can induce
biliary colic or result in false positive cholangiograms
-sphincter spasm may be less likely if the opioid is given slowly in small increments
These drugs have been reported to relieve opioid induced sphincter spasm
naloxone & glucagon
Mild postoperative liver dysfunction in healthy patients is not uncommon due to a combination of factors:
decreased hepatic blood flow
SNS stimulation
surgical procedures
Surgical procedures in close proximity to the liver frequently result in
modest elevations in lactate dehydrogenase & transaminases regardless of the anesthetic agent or technique employed
Postoperative elevation of liver function test are usually the result of
the procedure itself or underlying liver disease
Persistent abnormalities in liver function test may be indicative of:
viral hepatitis (usually transfusion related), sepsis, idiosyncratic drug reaction, & surgical complications
The most common cause of postoperative jaundice is
overproduction of bilirubin due to reabsorption of a large hematoma or RBC breakdown following transfusion
Hepatitis has been associated with these volatile anesthetics:
methoxyflurane, enflurane, & isoflurane
Hepatitis has not been associated with these volatile anesthetics:
sevoflurane, desflurane
Potential mechanisms for halothane hepatitis include:
formation of hepatotoxic metabolites & immune hypersensitivty
Risk factors associated with halothane hepatitis include:
middle age, obesity, female gender, repeated exposure particularly within 28 days- most important
Halothane hepatitis is a diagnosis of
exclusion
hepatitis from all viral causes should be excluded
Severity of halothane hepatitis can vary from
asymptomatic elevation of transaminases to fulminant hepatic necrosis
The liver has a great functional
reserve capacity
Clinical manifestations of hepatic disease are often
absent until extensive damage has occurred
In patients with significant liver disease with little reserve, anesthesia & surgery can
precipitate further hepatic injury & overt failure
Acute hepatitis is usually the result of
viral infection, drug reaction, exposure to a hepatotoxin
Clinical manifestation of acute hepatitis depends on
severity of the inflammatory reaction
& amount of cellular necrosis
In acute hepatitis, the severity of the inflammatory reaction may present as
asymptomatic elevations in serum transaminases
In acute hepatitis, the amount of cellular necrosis can lead to ____ & presents as
acute fulminant hepatic failure; presents as rapid, massive necrosis of liver parenchyma and a decrease in liver size
Acute hepatitis viral infections are most commonly due to
hepatitis A, B, or C viruses
Hepatitis A is transmitted by the
oral-fecal route
Hepatitis B & C are transmitted primarily
percutaneously and by contact with body fluids
Other viruses that may cause hepatitis include
D, E, Epstein-Bar, herpes simplex, cytomegalovirus, & coxsackievirsus
The hepatitis A form of viral hepatitis is (severity, recovery, & transmission)
least severe
most recover in weeks to months
transmission through fecal contamination
The hepatitis E form of viral hepatitis is (severity, transmission)
similar to A in terms of severity (least severe & most recover in weeks to months)
occurs in 3rd world countries
transmission through fecal contamination
The hepatitis D form of viral hepatitis does not
produce hepatitis by itself
only occurs as a co-infection with acute hepatitis B or super infection with chronic hepatitis B
severe infection in this setting
transmission through fecal contamination/body fluids
Summarize the Hep B form of viral hepatitis
HBsAg (surface antigen part of the virus)
often anicteric- doesn’t produce jaundice
can lead to fulminant hepatic necrosis or chronic hepatitis
HBsAg disappears with recovery but disease can be diagnosed by presence of hepatitis B antibody
transmission through sexual contact/blood
Summarize the Hep C form of viral hepatitis.
antibodies not present for long period- difficult to diagnose
subclinical nonicteric infection is common
rarely produces fulminant hepatic failure
a significant number of those who are chronically infected will develop cirrhosis or liver cancer- 20% develop cirrhosis/major cause of hepatocellular carcinoma
produces asymptomatic carriers
no effective vaccine currently available
transmission through blood
Patients suffering from acute hepatitis often have a
prodromal illness for 1 to 2 weeks with: fatigue, malaise, low-grade fever, nausea and/or vomiting
The prodromal period of acute hepatitis may or may not be followed by
jaundice- typically lasts 2 to 12 weeks complete recovery (evidenced by normal serum transaminases) usually takes 4 months
Clinical course of acute hepatitis tends to be
complicated and prolonged with hepatitis B & C viruses
Clinical manifestations from the causative agents overlap in acute hepatitis and therefore,
serological testing is necessary to determine the particular offending viral agent
The clinical course of drug-induced hepatitis resembles
viral hepatitis which makes diagnosis difficult
The most common cause of drug-induced acute hepatitis is
alcohol induced
Chronic alcohol ingestion can result in fatty infiltration as a result of:
impaired fatty acid oxidation
increased uptake & esterification of fatty acids
diminished lipoprotein synthesis & secretion
Acute drug-induced hepatitis results from
direct dose-dependent toxicity of a drug or a metabolite
idiosyncratic drug reaction
combination of the two
The incidence of chronic active viral hepatitis is
approx. 3 to 10% following infection with the B virus
at least 50% following infection with the C virus
A small percentage of patients with acute viral hepatitis become
asymptomatic infectious “carriers” of a hepatitis virus
Infectious carriers of hepatitis pose a major health threat to OR personnel:
avoid direct contact with blood & secretions
immunization is highly effective against hepatitis B infection
no vaccine for hep C available and prior infection does not confer immunity upon re-exposure
post-exposure prophylaxis with hyperimmune globulin is effective for hep B but not for C
