Pediatric Hematology

Question 1

When does liver started being produced?

Answer 1

3-4 weeks of gestation liver start

Question 2

Fetal liver takes over RBC production at

Answer 2

6 weeks of gestation

Question 3

BF shunted through______from Placenta to _______via _____

Answer 3

BF shunted through liver from placenta to RA via ductus venosus

Question 4

• Dual blood source

Answer 4

• Portal vein that drains spleen + intestine
  * >70% total BF
• Hepatic artery

Question 5

Blood flow

Answer 5

Blood goes through channels leading to a central vein →L/R hepatic vein → IVC

Question 6

Kids have________hepatocytes compared to adults

• Cells 1/3 size of adults

Answer 6

20% fewer hepatocytes

Question 7

STrutural unit of the liver is the

Answer 7

lobule

Question 8

2 things that go in the opposite direction

Answer 8

Bile and blood

Question 9

Functional unit of the liver is the

Answer 9

ACINUS

Question 10

Functional unit = hepatic acinus
• Extends into
• __________most active in oxidative process

Answer 10

three zones; Central zones (1,2)

Question 11

_________closest to central vein depends on glycolysis and most susceptible to ischemic/toxic injury

Answer 11

Distal zone 3

Question 12

Hepatic metabolism

Answer 12

Transforms lipid-soluble drugs to water-soluble metabolite compounds that are easily excreted by kidney
•

Question 13

• Primary liver enzyme =

Answer 13

cytochrome P- 450 (CYP)

Question 14

Two primary reactions

Answer 14

• Phase 1 = Hydroxylation (via CYP450)
• Prepares drug for conjugation
• Phase 2 = Conjugation (glucuronidation, sulfation,
glutathione, acetylation)

Question 15

CYP enzymes can be:

Examples

Answer 15

• Inhibited = compete for same enzyme

EXAMPLES: • Grapefruit juice, fluoxetine, quinidine, sulfaphenazole

Question 16

Induced =

Examples

Answer 16

enhanced expression →faster drug breakdown
• Tobacco smoke, phenytoin, rifampin, CHRONIC ALCOHOLISM (great requirement for anesthesia)
carbamazepine, phenobarbital.

Question 17

• CYP3A4 = most anesthetics

Answer 17

most abundant in human body, accounts for 50% of metabolism of clinically used pharmaceutical

Question 18

Inhalation anesthetic metabolism

Answer 18

Undergo oxidative and reductive reactions

Question 19

• Halothane broken down

Answer 19

(15-20%) to tri-fluoroacetyl →trifluoroacetic

acid (TFA) chloride

Question 20

• Isoflurane metabolized

Answer 20

0.2% →TFA (Trifluoroacetic acid)

Question 21

• Desflurane least metabolized

Answer 21

0.02% →TFA

Question 22

• Sevoflurane metabolized

Answer 22

2-5% to formyl fluoride

Question 23

Mnemonic to remember Metabolism from LEAST TO MORE METABOLIZED

Answer 23

DISH (0.02%–>0.2%–>2-5% –>15%)

Question 24

Does not break down to to TFA

Answer 24

Sevoflurane

Question 25

Liver issue patient

Answer 25

Give Sevoflurane

Question 26

Anesthetic agents : NMB drugs

Answer 26

Neuromuscular blocking drugs | • Plasma cholinesterase synthesized by liver

Question 27

• Hepatic elimination depends on

Answer 27

protein binding, hepatic BF, drug extraction

Question 28

• 75% of administered NMB bound to

Answer 28

plasma proteins

Question 29

• Volume of distribution________(inc/dec) with liver disease →

Answer 29

increased with ; lower concentrations

Question 30

• Peds c/cholestatic liver disease such as ________have ____uptake --> ___Plasma clearance + _____effects

Answer 30

(biliary atresia) have ↓uptake → ↓plasma clearance + | prolongs effects

Question 31

The more to the brain

Answer 31

the more effect it will have

Question 32

Greater VOLUME OF DISTRIBUTION

Answer 32

Specific one for each drug | Specific one for each patient

Question 33

Greater Vd give ____and _____maintenance dose

Answer 33

Greater BOLUS | Less maintenance dose.

Question 34

Obesity patients have

Answer 34

Increase Vd

Question 35

Sedatives including (3) are lipid soluble

Answer 35

Midazolam Propofol Ketamine

Question 36

Issue with ketamine

Answer 36

Give with something else Like versed | They can have bad dream remember DISSOCIATION

Question 37

Ketamine metabolized via -->

Answer 37

via methylation → clearance minimally affected by liver | dysfunction

Question 38

Opioids Clearance

Answer 38

• Hepatic clearance and protein binding determines serum concentration of an opioid

Question 39

Opioids: Most oxidized in________except (where) | Damaged li

Answer 39

liver (except remifentanil →plasma/tissue cholinesterases | • Damaged liver not as efficient → ↓first-pass effect/drug clearance

Question 40

First pass effect

Answer 40

Liver remove good majority of drugs for some drugs

Question 41

Fentanyl may get trapped in the

Answer 41

stomach

Question 42

(4) highly extracted by liver →

Answer 42

Meperidine, lidocaine, pentazocine, and morphine | perfusion limited clearance

Question 43

• Conditions that alter hepatic BF:

Answer 43

``` cirrhosis, portal vein thrombosis, portacaval shunting (blood shunted away from liver TIPS) ```

Question 44

• Methadone highly dependent

Answer 44

on enzyme capacity -->↑Half-life and volume of distribution

Question 45

Pharmacokinetics of ______ _____,______unchanged with significant hepatic dysfunction

Answer 45

fentanyl, remifentanil, and sufentanil

Question 46

Anesthetic Effects on Hepatic Cellular Function

Answer 46

Carbs | 50% of glucose available to liver undergoes glycolysis, 30-40% converted to fat, 10-20% shunted to glycogen

Question 47

Most glucose production normally occurs in

Answer 47

liver | • Indirectly regulated by insulin

Question 48

Glycogen breaks down to produce

Answer 48

glucose

Question 49

Anesthesia inhibits glucose uptake by_________

Answer 49

hepatocytes

Question 50

* All volatiles do this a little bit but______ | * This effect and stress from surgery →

Answer 50

@ 1-2MAC inhibition up to 50% | hyperglycemia

Question 51

• Protein synthesis | •

Answer 51

May be inhibited (rat studies) by sevoflurane | • May affect albumin

Question 52

Drug-induced liver injury : Diagnosis

Answer 52

• ↑ alanine aminotransferase (ALT) (MOST ACCURATE for liver) and aspartate aminotransferase (AST) (liver enzymes ↑alkaline phosphatase, bilirubin, gamma-glutamyl transferase (GGT)

Question 53

Liver enzymes are POOR markers of liver | function, only suggest

Answer 53

drug-induced injury

Question 54

• Liver functions best detailed by

Answer 54

PT/INR

Question 55

• Consider also for liver injury?

Answer 55

hypoalbuminemia, hypoglycemia AMS too

Question 56

______ and _______can induce CYP2E1, which may facilitate development of liver injury

Answer 56

• Obesity and hypercholesterolemia

Question 57

Perioperative considerations for Liver patients

Answer 57

Assess for hepatocellular and bile duct injury, coagulopathy, ascites, and encephalopathy

Question 58

• Presence of (2) contraindications to elective | surgery

Answer 58

hepatopulmonary syndrome | portopulmonary HTN

Question 59

• ________ ______results in more death perioperatively than in cirrhosis

Answer 59

Acute hepatitis

Question 60

• Stress from surgery

Answer 60

↓portal circulation, liver disease can limit compensate via hepatic artery = ischemia

Question 61

Percentage of blood going to portal

Answer 61

30%