Chemical Pathology Flashcards
Describe the pathogenesis of Pyphoria.
Porphyrigens are self-oxidizing and form porphyrins that react with UV light, leading to oxygen radicals in the skin, blisters, scars, and hypertrichosis
An increase in PBG and dALA mimics neurotransmitters and leads to CNS dysfunction.
How does fasting lead to acute porphyric attacks?
An increase in FA oxidation requires upregulation of PGC-1. PGC-1 leads to the build-up of the haem precursor dALA, which causes the acute attack.
List factors that may cause an acute porphyrin attack.
Puberty- sex hormones
Fasting
inducing of cytochrome p450
What are the signs/symptoms of an APA?
Abdominal pain- acute similar to surgical pain
Sen and motor neuropathy- weakness, bulbar palsy, resp paralysis
Autonomic Neuropathy- Tachycardia, Hypertension, Tachyarrythmia
anxiety, convulsions, psychosis
Hypo Na+
How do you manage APA?
Measure PBG and dALA
do not operate
Increase glucose
slowly correct Na+
ICU-ventilator
Haematologist- Haem increase, decrease haemoxgenase.
Describe Pyphoria Variegata.
AD
Afrikaans population
R59W single mutation of PPOX
Decrease PPOX
1/300
What are the tests for PV?
Protoporphyrin > Coprophyrin in stool
Plasma Fluorescence screening of protein-bound Protoporphyrin
Why can PV lead to an acute porphyrin attack?
A decrease in PPOX, leads to an increase in the protoporphyrinogen, and as a result, there is an inhibition of PBG deaminase and as a result an increase in precursors PBG and dALA
How do you diagnose PV?
Mutation analysis and Fluorescence screening.
How do you treat PV?
Treat acute attack if present
Provide sunscreen.
How do you diagnose APA?
Test for PBG and dALA in urine.
Why is PPOX required, if Protoporphyrinogen can spontaneously oxidise to protoporphyrin?
The process takes place in the mitochondria, a highly reduced environment.
What is the role of folate?
It carries a 1-carbon/methyl fragment required for
synthesis of purines and pyrimidine required for DNA synthesis. Furthermore, it is required for the methylation of homocysteine to form methionine.
What is the function of Vit B12?
It is a co-factor for Methionine synthases and Methylmalonyl-mutase.
Describe the relationship between folate and Vit B 12.
folate is required for the conversion of homocysteine to methionine of which Vit B12 is also required.