Pediatric Hematology Flashcards
When does liver started being produced?
3-4 weeks of gestation liver start
Fetal liver takes over RBC production at
6 weeks of gestation
BF shunted through______from Placenta to _______via _____
BF shunted through liver from placenta to RA via ductus venosus
• Dual blood source
- Portal vein that drains spleen + intestine
* >70% total BF - Hepatic artery
Blood flow
Blood goes through channels leading to a central vein →L/R hepatic vein → IVC
Kids have________hepatocytes compared to adults
• Cells 1/3 size of adults
20% fewer hepatocytes
STrutural unit of the liver is the
lobule
2 things that go in the opposite direction
Bile and blood
Functional unit of the liver is the
ACINUS
Functional unit = hepatic acinus
• Extends into
• __________most active in oxidative process
three zones; Central zones (1,2)
_________closest to central vein depends on glycolysis and most susceptible to ischemic/toxic injury
Distal zone 3
Hepatic metabolism
Transforms lipid-soluble drugs to water-soluble metabolite compounds that are easily excreted by kidney
•
• Primary liver enzyme =
cytochrome P- 450 (CYP)
Two primary reactions
• Phase 1 = Hydroxylation (via CYP450)
• Prepares drug for conjugation
• Phase 2 = Conjugation (glucuronidation, sulfation,
glutathione, acetylation)
CYP enzymes can be:
Examples
• Inhibited = compete for same enzyme
EXAMPLES: • Grapefruit juice, fluoxetine, quinidine, sulfaphenazole
Induced =
Examples
enhanced expression →faster drug breakdown
• Tobacco smoke, phenytoin, rifampin, CHRONIC ALCOHOLISM (great requirement for anesthesia)
carbamazepine, phenobarbital.
• CYP3A4 = most anesthetics
most abundant in human body, accounts for 50% of metabolism of clinically used pharmaceutical
Inhalation anesthetic metabolism
Undergo oxidative and reductive reactions
• Halothane broken down
(15-20%) to tri-fluoroacetyl →trifluoroacetic
acid (TFA) chloride
• Isoflurane metabolized
0.2% →TFA (Trifluoroacetic acid)
• Desflurane least metabolized
0.02% →TFA
• Sevoflurane metabolized
2-5% to formyl fluoride
Mnemonic to remember Metabolism from LEAST TO MORE METABOLIZED
DISH (0.02%–>0.2%–>2-5% –>15%)
Does not break down to to TFA
Sevoflurane
Liver issue patient
Give Sevoflurane
Anesthetic agents : NMB drugs
Neuromuscular blocking drugs
• Plasma cholinesterase synthesized by liver
• Hepatic elimination depends on
protein binding, hepatic BF, drug extraction
• 75% of administered NMB bound to
plasma proteins
• Volume of distribution________(inc/dec) with liver disease →
increased with ; lower concentrations
• Peds c/cholestatic liver disease such as ________have ____uptake –> ___Plasma clearance + _____effects
(biliary atresia) have ↓uptake → ↓plasma clearance +
prolongs effects
The more to the brain
the more effect it will have
Greater VOLUME OF DISTRIBUTION
Specific one for each drug
Specific one for each patient
Greater Vd give ____and _____maintenance dose
Greater BOLUS
Less maintenance dose.
Obesity patients have
Increase Vd
Sedatives including (3) are lipid soluble
Midazolam
Propofol
Ketamine
Issue with ketamine
Give with something else Like versed
They can have bad dream remember DISSOCIATION
Ketamine metabolized via –>
via methylation → clearance minimally affected by liver
dysfunction
Opioids Clearance
• Hepatic clearance and protein binding determines serum concentration of an opioid
Opioids: Most oxidized in________except (where)
Damaged li
liver (except remifentanil →plasma/tissue cholinesterases
• Damaged liver not as efficient → ↓first-pass effect/drug clearance
First pass effect
Liver remove good majority of drugs for some drugs
Fentanyl may get trapped in the
stomach
(4) highly extracted by liver →
Meperidine, lidocaine, pentazocine, and morphine
perfusion limited clearance
• Conditions that alter hepatic BF:
cirrhosis, portal vein thrombosis, portacaval shunting (blood shunted away from liver TIPS)
• Methadone highly dependent
on enzyme capacity –>↑Half-life and volume of distribution
Pharmacokinetics of ______ _____,______unchanged with significant hepatic dysfunction
fentanyl, remifentanil, and sufentanil
Anesthetic Effects on Hepatic Cellular Function
Carbs
50% of glucose available to liver undergoes glycolysis, 30-40% converted to fat, 10-20% shunted to glycogen
Most glucose production normally occurs in
liver
• Indirectly regulated by insulin
Glycogen breaks down to produce
glucose
Anesthesia inhibits glucose uptake by_________
hepatocytes
- All volatiles do this a little bit but______
* This effect and stress from surgery →
@ 1-2MAC inhibition up to 50%
hyperglycemia
• Protein synthesis
•
May be inhibited (rat studies) by sevoflurane
• May affect albumin
Drug-induced liver injury : Diagnosis
• ↑ alanine aminotransferase (ALT) (MOST ACCURATE for liver) and aspartate aminotransferase (AST) (liver enzymes
↑alkaline phosphatase, bilirubin, gamma-glutamyl transferase (GGT)
Liver enzymes are POOR markers of liver
function, only suggest
drug-induced injury
• Liver functions best detailed by
PT/INR
• Consider also for liver injury?
hypoalbuminemia,
hypoglycemia
AMS too
______ and _______can induce CYP2E1, which may facilitate development of liver injury
• Obesity and hypercholesterolemia
Perioperative considerations for Liver patients
Assess for hepatocellular and bile duct injury, coagulopathy, ascites, and encephalopathy
• Presence of (2) contraindications to elective
surgery
hepatopulmonary syndrome
portopulmonary HTN
• ________ ______results in more death perioperatively than in cirrhosis
Acute hepatitis
• Stress from surgery
↓portal circulation, liver disease can limit compensate via hepatic artery = ischemia
Percentage of blood going to portal
30%
