Heme Metabolism - Goueli

Question 1

Your patient has TB and is being treated with isoniazid. Recently, the patient has been experiencing peripheral neuropathy and other CNS effects. Why?

Answer 1

Vitamin B6 (pyridoxine) deficiency

Question 2

What two enzymes in the heme metabolism pathway can be affected by lead toxicity?

Answer 2

Ferrocheletase and delta-ALA dehydratase

Question 3

Protoheme regulates its own production by repressing what enzyme?

Answer 3

delta-ALA synthase synthesis and activity

Question 4

Protoheme also regulates the synthesis of _______ in the active state.

Answer 4

globin –> catalyzes the conversion of protoheme to hemoglobin

Question 5

What type of anemia results when hemoglobin cannot be produced?

Answer 5

Microcytic anemia due to lead poisoning

Question 6

Heme is degraded to ______.

Answer 6

Bilirubin

Question 7

Where is bilirubin is converted to a more water soluble compound?

Answer 7

The LIVER!

Question 8

What is the conjugated form of bilirubin called?

Answer 8

Diglucuronide

Question 9

Direct Bilirubin

Answer 9

Conjugated in the liver

Question 10

When are direct, conjugated bilirubin levels elevated?

Answer 10

Biliary obstruction, gallstone, bile not getting out of the liver

Question 11

Indirect Bilirubin

Answer 11

Unconjugated

Question 12

When are the indirect, unconjugated bilirubin levels elevated?

Answer 12

Hemolysis in the vasculature

Question 13

What is the #1 most common porphyria?

Answer 13

Porphyria Cutanea Tarda (non-life threatening)

Question 14

Acute Porphyria

Answer 14

ALA and PBG increased due to reduced PBG deaminase activity

Question 15

Non-Acute or Cutaneous Porphyria

Answer 15

ALA and PBG not increased due to increased PBG deaminase activity

Question 16

PBG

Answer 16

Prophobilinogen

Question 17

ALA

Answer 17

Delta-Aminolevulinic Acid

Question 18

Acute Porphyria Symptoms

Answer 18

Vague abdominal pain, CNS, tachycardia, hypertension

Question 19

Acute Intermittent Porphyria Symptoms

Answer 19

GI pain, vomiting, constipation, hyponatremia (low sodium), neuropathy, CV

Question 20

Risk for what cancer is increased with Acute Intermittent Prophyria?

Answer 20

Hepatocellular Carcinoma

Question 21

Clinical sign of Acute Intermittent Porphyria

Answer 21

Clear urine but darkens with light exposure as prophyrinogens are oxidized to porphyrins

Question 22

Hereditary Coproporphyria

Answer 22

Acute Intermittent Porphyria symptoms with Photosensitivity

Question 23

Almost all prophyrias are passed on genetically through…

Answer 23

Autosomal Dominant

Question 24

ALA Dehydratase Deficiency is genetically passed on through…

Answer 24

Homozygous Autosomal Recessive

Question 25

Diagnosis of ALA Dehydratase Deficiency

Answer 25

High delta-ALA, normal PBG

Question 26

Treatment of Acute Porphyrias

Answer 26

Remove the stressor, suppress ovulation, IV fluids, pain control, withdraw medications, seizure precautions for hyponatremia

Question 27

Management of chronic porphyria syndromes

Answer 27

Carbohydrates to decrease porphyrin synthesis, IV hematin (in order to prevent the pathway), suppress ovulation

Question 28

Porphyria Cutanea Tarda

Answer 28

Deficiency of hepatic uroporphyrinogen decarboxylase (URO-D) causing increased iron stores; 50% of patients with sporadic form are Hepatitis C positive

Question 29

Symptoms of Porphyria Cutanea Tarda

Answer 29

Bullous Dermatosis, Scarring, Hyperpigmentation, Hypertrichosis

Question 30

What does an elevated uroporphyrin level indicate?

Answer 30

Porphyria Cutantea Tarda

Question 31

What is the treatment for Porphyria Cutanea Tarda?

Answer 31

Phlebotomy 500 mL (1 unit = 250 mg Fe) per week until remission