Gastroenterology Flashcards
At birth, the fetal supply of glucose is abruptly interrupted. How do neonates meet their glucose needs?
1) glucose intake (feeding)
2) gluconeogenesis
3) glycogenolysis
How does the liver of term infants compare to the adult in terms of glycogen stores?
The term infant has a greater store of glycogen than the adult. Preterm infants have less glycogen stores and are predisposed to hypoglycemia.
When is gluconeogenesis active in the fetal liver?
Gluconeogensis is NOT active in the fetal liver but hepatic enzymes that are involved such as glucose-6-phosphatase undergo rapid development after birth.
What are normal glucose levels for a neonate?
40 - 60 mg/dL
Below what glucose level defines hypoglycemia in a neonate?
Below 40 mg/dL
What infusion rate of glucose in terms of mg/kg/min maintains normoglycemia in both full-term and pre-term infants?
4 to 7 mg/kg/min
What are symptoms of hypoglycemia in a neonate?
Nonspecific symptoms such as jitteriness, cyanosis, apnea, lethargy, seizures and hypotonia
What are three common causes of hypoglycemia in neonates?
1) hypoxemia
2) sepsis
3) high levels of circulating insulin
What is Phase I liver biotransformation?
oxidation-reduction and hydrolysis performed by cytochrome p450 enzymes
What is Phase II liver biotransformation?
conjugation with glucoronic acid, glycine, acetate, or sulfate to form a more water soluble conjugate. Decreasing the lipid solubility facilitates excretion
What is Phase III liver biotransformation?
Transport from liver
How does the neonatal capacity for the various phases of liver metabolism compare to that of the adult or more mature child?
Neonates have a reduced capacity for Phase I and 2 reactions.
Which CYP family is responsible for approximately 50% of all drug metabolism?
CYP3A
Which CYP is present in utero but is negligibly expressed one week after birth?
CYP3A7
Describe the expression of CYP3A4 in the fetus, neonate and infant.
CYP3A4 levels are very low during fetal life but reach 50% of adult levels by 6 months of age.
Which CYP has a multitude of polymorphisms that are of particular relevance in the metabolis of psychotropic and anesthetic drugs?
CYP2D6
What enzyme is associated with Phase II biotransformation in the liver?
UGT (aka, uridine-5-diphosphate-glucoronyltransferase)
How does glucoronidation activity in the neonate/infant compare to that of the adult?
Glucoronidation is a Phase II biotransformation process in the liver facilitated by UGTs. UGT levels are low in neonates and infants, thus glucoronidation is not fully active. At 3 months of age UGT levels are 25% that of adults. This places infants at risk for toxic drug accumulation.
What phase of liver biotransformation is responsible for the metabolism of many opioids?
Phase II - Conjugation. The responsible enzyme is UGT.
What liver enzyme metabolizes acetaminophen?
UGT1A6 (phase II conjugation)
What liver enzyme metabolizes naproxen?
UGT1A6 (phase II conjugation)
Describe the expression of UGT1A6 in neonates and infants are compared to adult levels.
UGT1A6 has 10% of adult expression in the fetus and only 50% of adult activity by 6 months of age.
What liver enzyme metabolizes naloxone?
UGT2B7
What liver enzyme metabolizes codeine?
UGT2B7
What liver enzyme metabolizes lorazepam?
UGT2B7
Describe the expression of UGT2B7 in neonates and infants are compared to adult levels.
Fetal activity approaches 10% - 20% of adult levels with a rapid increase to adult levels by 2 months of age.
Where do fetal circulating coagulation factors come from?
They are made by the fetus because they inefficiently cross the placenta.
How do plasma concentrations of vitamin K derived factors in the fetus compare to the adult?
They are about 50% lower than adult levels.
How do the concentrations of fibrinogen, factor V, and factor VIII compare to those of adults?
They are similar (i.e., about the same).
What type of cell is responsible for producing the factors that affect PT?
Hepatocytes synthesize factors 1 (fibrinogen), II (prothrombin), V, VII, IX, and X and abnormal production of these factors is reflected in a prolonged PT. PT mostly reflects availability of factor VII.
How do neonatal thrombin levels compare to those of adults?
Neonatal thrombin levels are about 50% those of adults.
What coagulation study reflects the amount of generated thrombin?
aPTT
How do infections or asphyxia affect coagulation in the newborn?
In the newborn, both of these can cause DIC.
How might rapid infusion of FFP affect neonatal blood pressure?
Because FFP contains high concentrations of histamine and citrate, rapid infusion can cause histamine-related hypotension as well as hypotension from citrate toxicity (i.e., hypocalcemia)
What is the primary parent source of bilirubin?
Hemoglobin (but cytochromes, catalases and myoglobin also contribute as they also contain heme)
Would you expect a neonate who suffered significant hemolysis in utero to be jaundiced?
No because the normal placenta efficiently clears bilirubin.
Would you expect a neonate who suffered significant hemolysis at birth to be jaundiced?
Yes.
When should neonatal jaundice be considered abnormal?
It is abnormal if any of the following conditions are true:
1) present in the first 36 hours of life
2) persists beyond 10 days of life
3) is greater than 12 mg/dL and the direct (conjugated) bilirubin is greater than 2mg/dL or more than 30% of the total bilirubin concentration
What type of bilirubin is responsible for the physiologic jaundice of the newborn?
Indirect (unconjugated) bilirubin
What is the predominant feature of kernicterus?
Neuronal necrosis which occurs mostly in the basal ganglia, brainstem, oculomotor nuclei, and cochlear nuclei.
What type of bilirubin contributes to the hyperbilirubinemia of sepsis?
Direct (conjugated) bilirubin
What is the “anti-insulin effect of anesthesia?”
It is the inhibition of glucose uptake by hepatocytes caused by anesthetics. Halothane has the greatest impact on serum glucose with iso and sevo having lesser effects.
What is the effect of 1 to 2 MAC of an inhalational anesthetic on glucose uptake by hepatocytes?
Glucose uptake is INHIBITED by up to 50%!
Why are glucose-containing IV fluids no longer recommended for most healthy children undergoing elective surgery?
Because the combination of anti-insulin effect of anesthesia and the stress from surgery or trauma increase the serum glucose concentration.
How do inhaled anesthetics affect protein synthesis?
Halothane and enflurane block protein synthesis in a dose dependent manner.
Halothane, sevoflurane, and enflurane inhibit protein synthesis and secretion.
What sort of normal changes are expected in serum aminotransferase concentrations and bilirubin levels in the postoperative period?
Increases in serum aminotransferase concentrations and bilirubin up to two times the upper limit of normal occur commonly in the postoperative period and are typically self-limited and inconsequential.
What LFT changes would you expect with hepatocellular injury?
Predominantly increased ALT and AST levels
What LFT changes would you expect with cholestatic hepatotoxicity?
increases in alkaline phosphatase, GGT, and bilirubin
Is perioperative mortality greater in those with acute hepatitis or those with chronic liver disease?
Those with acute hepatitis.
When would you expect the development of parenteral nutrition-associated liver disease to occur?
After 60 days of parenteral nutrition use
How does exposure to TPN affect perioperative glucose control?
Those exposed to TPN are at increased risk of perioperative glucose derangements and frequent perioperative glucose monitoring with adjustment of dextrose infusion is standard of care.
When does a child with biliary atresia typically present to the hospital?
1 - 6 weeks of age
What abnormalities are associated with biliary atresia?
In 10 - 15% of those patients: Absent IVC intestinal malrotation Polysplenia Preduodenal portal vein
What is another name for the Kasai procedure?
Hepatic portoenterostomy
At what age is the Kasai procedure most successful?
The success rate is 80% in those operated on before 2 months of age and 50% in those operated on before 4 months of age
What percentage of patients who have undergone a Kasai procedure go on to becoming liver transplant candidates?
80%
What volatile agent is preferred for a Kasai procedure?
Isoflurane anesthesia maintains better hepatic blood flow and oxygen supply.
What is adriamycin?
Adriamycin is an anthrcycline chemotherapeutic agent that causes a dosage-dependent irreversible cardiomyopathy.
What causes the vast majority of death in fulminant hepatic failure?
Increased ICP with cerebral herniation is responsible for 80% of death in fulminant hepatic failure.
Cerebral perfusion pressure should be maintained above what value?
Greater than 50 mmHg
Define portopulmonary hypertension.
Portal hypertension with pulmonary systolic pressure > 25 mmHg with normal PCWP.
Where is vWF produced?
The endothelium
All factor levels are decreased in liver disease except for which factor(s)?
Fibrinogen and Factor VIII
What are the primary etiologies of liver disease that require liver transplantion in children?
Biliary atresia (50% of infantile transplants)
Cholestatic liver disease (e.g. TPN cholestasis)
Liver failure 2/2 toxins or tumors
Metabolic diseases
What are the notable differences in patients with metabolic diseases presenting for liver transplantation as compared to other patients?
Metabolic disease patients generally do NOT have liver dysfunction (i.e., no coagulopathy, no cirrhosis, no collateral vessels) and may be susceptible to metabolic crises.
What is the pathophysiology of maple syrup urine disease?
Leucine accumulation as a result of metabolic error for branched-chain amino acids (leucine, isoleucine, valine).
What is the normal action of Alpha-1 Antitrypsin?
A1AT inhibits neutrophil protease in setting of inflammation, this when A1AT levels are low there is excessive tissue injury during inflammation.
What are the anesthetic concerns during the anhepatic phase of liver transplantation?
Hypothermia Hypoglycemia Hypocalcemia/Citrate toxicity Metabolic Acidosis Loss of venous return Decreased renal perfusion due to renal venous obstruction
What does the term “physiologic GERD” in the pediatric population refer to?
GERD that is 2/2 immature lower esophageal sphincter mechanism that generally resolves by 15 months of age.
