Lecture 12: Heme, Bilirubin, Porphyria II

Question 1

Why is neonatal jaundice so common?

Answer 1

Developmental delay in UGT expression; before birth, maternal circulation clears BR

Question 2

Kernicterus

Answer 2

Newborns don’t have a BBB yet, so accumulation of unconjugated BR can become toxic to the NS

Question 3

Treatment of neonatal jaundice

Answer 3

Light cleaves unconjugated BR into non-toxic products and babies have thinner skin + more relative surface area

Question 4

Types of hepatic porphyria

Answer 4

1. Acute intermittent (PBG deaminase)
2. Cutanea tarda (uro’gen III DC)
3. Hereditary coprophyria (copro’gen III DC)
4. Variegate (protogen IX DH)

Question 5

Characteristics of photosensitive porphyrias

Answer 5

PCT, HC, and VP are photosensitive because o’gen intermediates accumulate. Only o’gen intermediates can be oxidized by light to generate free radicals.

Question 6

Why is PCT a chronic porphyria?

Answer 6

PCT can be non-genetic, caused by underlying chronic Hep C, alcohol use, HIV. This makes it the only chronic hepatic porphyria.

Question 7

What makes prophyrias acute?

Answer 7

Genetic prophyria is heterozygous, so 50% enzyme capacity. Usually asymptomatic until a precipitating increase in heme utilization (drugs, hormones, alc., etc.) means no heme is left to autoregulate ALAS, leading to a toxic buildup of ALAS/other intermediates.

Question 8

How do chronic hep C, EtOH use, and HIV cause chronic PCT?

Answer 8

These conditions increase iron absorption/liver deposition, leading to iron overload and hepatic inflammation. More iron = more oxidative stress = more partial oxidation of uro’gen III to uroprophomethane which inhibits uro’gen III DC (PCT).