Heme Metabolism Flashcards
In hemolysis you will see increased. . .
. . .indirect (unconjugated) bilirubin.
In biliary obstruction you will see. . .
. . .direct (conjugated) bilirubin.
What is the association between sporadic and Hep C in porphyria cutanea trada?
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What is the B6 limitation with respect to Isoniazid and TB?
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How is heme degraded?
To form bilirubin which is conjugated with glucuronic acid and excreted in the bile
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
Source of bile pigment:
Hemoglobin
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
What is B6 deficiency associated with?
Microcytic, hypochormic anemia due to slowed heme production as delta-ALA synthase requires pyridoxal phosphate
What is B6 deficiency associated with?
Microcytic, hypochormic anemia due to slowed heme production as delta-ALA synthase requires pyridoxal phosphate (pyridoxine = vitamin B6)
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)
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!
Where is bilirubin conjugated??
IN THE LIVER
What could block direct (conjugated) bilirubin?
Biliary obstruction - tumor in the bowel
What is abdominal pain + CNS symptoms =
Acute Porphyrias!
What is abdominal pain + CNS symptoms =
Acute Porphyrias!
-Almost all are autosomal dominant
What is the #1 symptoms of acute porphyria?
#1 abdominal pain -Vomiting, constipation, diarrhea, neurological symptoms
What is a porphyria?
Inherited disorder that results from deficiencies in enzymes in pathway for heme biosynthesis
Acute Intermittent Porphyria may cause long term what?
Long term increased risk of hepatocellular carcinoma
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
What do you want to give the patient with Acute porphyries?
HEME!! (IV hematin, heme arginate, hematin)
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
When do you need to do tests?
WHEN PATIENT IS SYMPTOMATIC
What is porphyria cutanea trade?
- Deficiency of hepatic uroporphyrinogen decarboxylase (URO-D) - in heme synthesis pathway
- Auto. dom. inheritance
- Most common porphyria
