Heme Metabolism

Question 1

In hemolysis you will see increased. . .

Answer 1

. . .indirect (unconjugated) bilirubin.

Question 2

In biliary obstruction you will see. . .

Answer 2

. . .direct (conjugated) bilirubin.

Question 3

What is the association between sporadic and Hep C in porphyria cutanea trada?

Answer 3

fill in

Question 4

What is the B6 limitation with respect to Isoniazid and TB?

Answer 4

fill in

Question 5

How is heme degraded?

Answer 5

To form bilirubin which is conjugated with glucuronic acid and excreted in the bile

Question 6

What is the B6 limitation with respect to Isoniazid and TB?

Answer 6

Isoniazid:

• Can cause B6 deficiency resulting in peripheral neuropathy, CNS effects and anemia
• Consider supplementation in patients in which neuropathy is common (e.g. diabetes, uremia, alcoholism, malnutrition, and HIB), pregnant women and persons with seizure disorder

Question 7

Source of bile pigment:

Answer 7

Hemoglobin

Question 8

When RBCs reach the end of life (after 120 days):

Answer 8

• They are phagocytose by cells of the RES
• Globin is cleaved to its constituent AAs and iron is returned to the body
• Heme is oxidized and cleaved to produce carbon monoxide and biliveridin
• Biliberidin is reduced to bilirubin which is transported to the liver complexed with serum albumin
• In liver, bilirubin is converted to more water soluble compound by reacting with UDP-glucuronate to form bilirubin monoglucuronide, which is covered to diglucuronide
• Then excreted in bild
• Converted to urobilinogens by bacteria in intestine
• Some goes to blood, some urine, some stool

Question 9

What is B6 deficiency associated with?

Answer 9

Microcytic, hypochormic anemia due to slowed heme production as delta-ALA synthase requires pyridoxal phosphate

Question 10

What is B6 deficiency associated with?

Answer 10

Microcytic, hypochormic anemia due to slowed heme production as delta-ALA synthase requires pyridoxal phosphate (pyridoxine = vitamin B6)

Question 11

When RBCs reach the end of life (after 120 days):

Answer 11

• They are phagocytose by cells of the RES
• Globin is cleaved to its constituent AAs and iron is returned to the body
• Heme is oxidized and cleaved to produce carbon monoxide and biliveridin
• Biliberidin is reduced to bilirubin which is transported to the liver complexed with serum albumin
• In liver, bilirubin is converted to more water soluble compound by reacting with UDP-glucuronate to form bilirubin monoglucuronide, which is covered to diglucuronide
• Then excreted in bile
• Converted to urobilinogens by bacteria in intestine
• Some goes to blood, some urine
• Most oxidized to urobilins (like stercobilin) and excreted in feces (brown color)

Question 12

Where is bilirubin converted to a more water soluble compound (conjugation process in excretion) by reacting with UDP-glucuronate to form bilirubin monogluonide, which is converted to diglucuronide?

Answer 12

LIVER!

Question 13

Where is bilirubin conjugated??

Answer 13

IN THE LIVER

Question 14

What could block direct (conjugated) bilirubin?

Answer 14

Biliary obstruction - tumor in the bowel

Question 15

What is abdominal pain + CNS symptoms =

Answer 15

Acute Porphyrias!

Question 16

What is abdominal pain + CNS symptoms =

Answer 16

Acute Porphyrias!

-Almost all are autosomal dominant

Question 17

What is the #1 symptoms of acute porphyria?

Answer 17

#1 abdominal pain 
-Vomiting, constipation, diarrhea, neurological symptoms

Question 18

What is a porphyria?

Answer 18

Inherited disorder that results from deficiencies in enzymes in pathway for heme biosynthesis

Question 19

Acute Intermittent Porphyria may cause long term what?

Answer 19

Long term increased risk of hepatocellular carcinoma

Question 20

Acute Intermittent Porphyria - Signs and symptoms:

Answer 20

• GI: pain, vomiting, constipation, on exam abdomen is tender, but not rigid
• Hyponatremia in a severe attack
• Neuropathy (2/3): motor, sensory, physchiatric
• CV: increased BP, tachycardia
• PHOTOSENSITIVITY NOT PRESENT

Question 21

What do you want to give the patient with Acute porphyries?

Answer 21

HEME!! (IV hematin, heme arginate, hematin)

Question 22

What is the association between sporadic and Hep C in porphyria cutanea trada?

Answer 22

> 50% of patients with sporadic form are HCV positive

-May be a precipitating factor

Question 23

When do you need to do tests?

Answer 23

WHEN PATIENT IS SYMPTOMATIC

Question 24

What is porphyria cutanea trade?

Answer 24

• Deficiency of hepatic uroporphyrinogen decarboxylase (URO-D) - in heme synthesis pathway
• Auto. dom. inheritance
• Most common porphyria

Question 25

What are precipitating factors of porphyria cutanea trada?

Answer 25

• Increased iron stores (down regulation of hepcidin)
• Hepatitis C
• Estrogens

Question 26

Porphyria Cutanea Tarda symptoms:

Answer 26

• Bullous dermatosis (blistering skin lesions)
• Scarring
• Hyperpigmentation
• Hypertrichosis

Question 27

Porphyria Cutanea Tarda symptoms:

Answer 27

• Bullous dermatosis (blistering skin lesions)
• Scarring
• Hyperpigmentation
• Hypertrichosis
• -See bullous lesion in sun exposed regions

Question 28

How to treat PCT?

Answer 28

• Avoid precipitating factors (eg. alchohol)
• Phlebotoomy until in remission
• Iron chelation if phlebotomy not possible

Question 29

When do you need to do tests for Porphyrias?

Answer 29

WHEN PATIENT IS SYMPTOMATIC

-They may have normal heme precursor levels during asymptomatic periods

Question 30

What do you always see in symptomatic porphyria?

Answer 30

Increased heme precursors!