Heme Metabolism Flashcards Preview

IHO Week 1 > Heme Metabolism > Flashcards

Flashcards in Heme Metabolism Deck (30):
1

In hemolysis you will see increased. . .

. . .indirect (unconjugated) bilirubin.

2

In biliary obstruction you will see. . .

. . .direct (conjugated) bilirubin.

3

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

fill in

4

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

fill in

5

How is heme degraded?

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

6

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

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

7

Source of bile pigment:

Hemoglobin

8

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

-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

9

What is B6 deficiency associated with?

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

10

What is B6 deficiency associated with?

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

11

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

-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)

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?

LIVER!

13

Where is bilirubin conjugated??

IN THE LIVER

14

What could block direct (conjugated) bilirubin?

Biliary obstruction - tumor in the bowel

15

What is abdominal pain + CNS symptoms =

Acute Porphyrias!

16

What is abdominal pain + CNS symptoms =

Acute Porphyrias!
-Almost all are autosomal dominant

17

What is the #1 symptoms of acute porphyria?

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

18

What is a porphyria?

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

19

Acute Intermittent Porphyria may cause long term what?

Long term increased risk of hepatocellular carcinoma

20

Acute Intermittent Porphyria - Signs and symptoms:

-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

21

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

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

22

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

>50% of patients with sporadic form are HCV positive
-May be a precipitating factor

23

When do you need to do tests?

WHEN PATIENT IS SYMPTOMATIC

24

What is porphyria cutanea trade?

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

25

What are precipitating factors of porphyria cutanea trada?

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

26

Porphyria Cutanea Tarda symptoms:

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

27

Porphyria Cutanea Tarda symptoms:

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

28

How to treat PCT?

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

29

When do you need to do tests for Porphyrias?

WHEN PATIENT IS SYMPTOMATIC
-They may have normal heme precursor levels during asymptomatic periods

30

What do you always see in symptomatic porphyria?

Increased heme precursors!