Heme synthesis

Question 1

What is needed for ALA synthase?

Answer 1

Vit B6

Deficiency→anemia

Question 2

Defective ALA dehydratase symptoms

Answer 2

Acute attacks of abdominal pain and neuropathy

Question 3

Defective PBG deaminase (in liver)

Answer 3

Acute intermittent porphyria: abdominal pain, neurologic dysfunction

Type: hepatic

Question 4

Defective Protoporphyrinogen IX oxidase

Answer 4

Variegate porphyria: photosensitivity, developmental delay in children

Type: Hepatic

Question 5

Defective Ferrochelatase

Answer 5

Erythropoietic protoporphyria: Photosensitivity w/ skin lesions after brief sun exposure, gallstones, mild liver dysfunction

Type: erythropoietic

Question 6

Unconjugated (“indirect”) bilirubin

Answer 6

Hemoglobin is broken down, heme is then turned into unconjugated bilirubin in the spleen. This unconjugated bilirubin is insoluble in water. It is then bound to albumin and sent to the liver.

Question 7

Conjugated (“direct”) bilirubin

Answer 7

In the liver, bilirubin is conjugated with glucuronic acid by the enzyme glucuronyltransferase, making it soluble in water

Question 8

Jaundice

Answer 8

Too much bilirubin or not getting rid of it correctly

Question 9

Pre-hepatic jaundice (hemolytic)

Answer 9

↑ unconjugated bilirubin

• hemolytic anemias
• internal hemorrage
• G6P dehydrogenase deficiency
• Neonatal jaundice due to problem w/ maternal/fetal blood groups (baby’s conjugation enzymes aren’t up and running yet when it’s trying to get rid of fetal Hb)

Symptoms: 
↑ unconjugated BR
-normal conjugated BR
-normal ALT & AST
-Urobilinogen present in urine

Question 10

Intra-hepatic jaundice

Answer 10

-Impaired hepatic uptake, conjugation, or secretion ofconjugated BR

Liver dysfunction

• liver cirrhosis
• viral hepatitis
• Criggler-Najjar syndrom
• Gilbert syndrom

Symptoms:

• ↑ALT/AST
• urobilinogen present in urine
• conjugated BR detected in urine

Question 11

Post-hepatic

Answer 11

• Problems w/ release
• Cholestasis (decreased bile flow)

Symptoms:
↑ blood conjugated BR w/ much smaller increases in unconjugated form
-Normal ALT/AST
↑ ALP
↑ bile salts (b/c preventing release)
-Urine is dark
-Conjugated BR in urine
-No urobilinogen in urine
-Pale stool

Question 12

Neonatal jaundice

Answer 12

• Deficiency of UDP-GT enzyme
• Immature hepatic pathways-unable to conjugate and excrete bilirubin

Treatment: UV light–>breaks down bilirubin

Question 13

Criggler-Najjar syndrome

Answer 13

Cause: UDP-GT deficiency

Type 1: complete loss of gene

Symptoms:
-severe hyperbilirubinemia (accumulates in brain of affected newborns–>causes kernicturus)

Treatment:

• Phototherapy
• Blood transfusions
• Heme oxygenase inhibitors
• Oral Calcium phosphate
• Liver translation

Type 2: benign form (mutation in gene)

Question 14

Gilbert Syndrome

Answer 14

Reduced activity of UDP-GT activity. Not as serious as Crigler-Najjar

Serum BR

Question 15

Hepatitis

Answer 15

Liver inflammation

• Leads to liver dysfunction
• Causes ↑ levels conjugated/unconjugated BR in blood
• Accumulates in skin & sclera of eyes→yellow discoloration, urine is tea colored