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Hematology > 10.15.18 Porphyrias > Flashcards

10.15.18 Porphyrias Flashcards

1
Q

These are a group of metabolic disorders resulting from a mutation in one of the enzymes in the heme biosynth pathway that leads to the accumulation of toxic metabolites; inherited/sporadic

A

Porphyria

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2
Q

Toxic metabolites from the heme biosynth pathways that have no useful function and act as highly reactive oxidants/damage tissue

A

Porphyrins

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3
Q

First (and rate-limiting) enzyme in heme synthesis pathway

mitochondrial enzyme that catalyzes the conversion of glycine and succinyl CoA to form delta-aminolevulinic acid and requires pyridoxal-5’-phosphate as a cofactor

A

Aminolevulinic acid synthetase (ALAS)

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4
Q

How can we induce ALAS1?

Why do we care?

A
  1. Depletion of the hepatic pool of heme
  2. Drugs, hormones which induce CYPs (and ALAS1)
  3. Caloric and carbohydrate restriction
  4. Metabolic stress, may induce hepatic heme oxygenase and accelerate heme destruction

Bad if you have porphyria and toxic metabolites from ALAS production form

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5
Q

What is Acute Intermittent Porphyria caused by?

A

Deficiency of hepatic PBG deaminase

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6
Q

Pattern of inheritance for AIP?

A

Autosomal dominant with low penetrance

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7
Q

In addition to low levels of PBGD what else does AIP require?

A

Induction of ALAS1

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8
Q

What are clinical features of an acute attack for AIP?

A
  1. Abdominal pain
  2. High HR/BP
  3. No inflammatory signs
  4. Sensory/motor neuropathy
  5. Insomnia
  6. Seizure
  7. Increase catecholamines
  8. SIADH- Hyponatremia
  9. Dark/reddish brown urine
  10. Bulbar paralysis, respiratory impairment, death
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9
Q

What are exacerbating factors of an acute attack?

A
  1. Drugs
  2. Crash diets
  3. Endogenous hormones
  4. Cigarette smoking
  5. Metabolic stresses
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10
Q

How do you diagnose AIP?

A
  • Send urine for PBG and ALA to see if they’re elevated
  • If markedly elevated send PBG deaminase enzyme activity
  • DON’T be fooled by elevation in urine/stool porphyrins
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11
Q

How do you treat AIP?

A
  1. Withdraw unsafe meds

2. IV 10% glucose and hematin

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12
Q

How does Hematin work?

A

Reduces ALA/porphyrin by negative feedback inhibition on ALA synthetase

Degradation products binding can cause adverse effects of low platelets (thrombophlebitis, anticoagulation, thrombocytopenia) and iron overload

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13
Q

This is caused by a deficiency of uroporphyrinogen decarboxylase (UROD)

A

Porphyria Cutanea Tarda (PCT)

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14
Q

How are UROD level activity diminished?

A

Iron overload/dysregulation of hepcidin

hepatic iron levels are correlated with clinical expression

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15
Q

What are associated disorders with PCT?

A
  1. Alcoholism
  2. Hemochromatosis
  3. Hepatitis C
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16
Q

What are the clinical manifestation of PCT?

A

Skin problems/increased growth of hair on cheeks/forearms (hirsutism)

Liver damage (increase AST/ALT levels)

17
Q

What are you at an increased risk for with PCT?

A
  1. Cirrhosis

2. Hepatocellular carcinoma

18
Q

How do you diagnose PCT?

A
  1. Screening test for total plasma porphyrin levels
  2. ALA and PBG normal since ALAS isn’t induced
  3. Confirmatory testing
19
Q

How do you treat PCT?

A
  1. No alcohol
  2. Withhold estrogen
  3. Stop smoking
  4. Cover sun exposed areas
  5. Phlembotomy to remove iron
20
Q

What is the safe level of lead in children?

A

There is none

21
Q

What are sources of lead exposure in adults?

A

Inhaled

  1. Leaded gasoline
  2. Lead paint
  3. Moonshine
22
Q

What are sources of lead exposure in children?

A

Ingested

  1. Cosmetics/folk remedies
  2. Ingested paint, water, food
23
Q

How does lead poisoning affect the heme synthesis pathway?

A

Inhibit ALAS and ferrochelatase

24
Q

What will you see in a blood smear with lead poisoning?

A

Basophilic stippling

25
Q

What are the clinical manifestations of lead toxicity?

A
  1. Lead colic
  2. Anemia (microcytic)
  3. Lead line
  4. Neuropsychiatric effects
  5. Gout/Saturnine gout
  6. Wrist and foot drop
26
Q

How do you diagnose lead toxicity?

A

Blood lead levels (>10 for adults, >5 for children)

Venous stick

27
Q

How do you manage lead toxicity

A
  1. Reduce lead exposure
  2. Chelation therapy- need to curtail exposure first bc use of therapy can enhance absorption of lead thereby worsening symptoms

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