Porphyrias

Question 1

mechanism of porphyria diseases

Answer 1

problem with enzyme in production of the porphyrin ring for heme leads to build up of oxidizing metabolites that can damage tissues

Question 2

what cell is heme made in?

Answer 2

all damn cells

Question 3

how do we induce ALAS1 and AIP porphyrias?

Answer 3

depletion of hepatic pool of heme, drugs/hormones inducing CYPs, caloric or carb restriction, metabolic stress

Question 4

What does ALAS stand for?

Answer 4

Aminolevulinic acid synthetase

Question 5

What is the reaction with ALAS?

Answer 5

turning succinyl coa and glycine into aminolevulinic acid

Question 6

Why is ALAS important?

Answer 6

if we have condition that induces ALAS but there is a downstream porphyria then we will get build up of the porphyrin metabolites and worsening porphyria

Question 7

Acute intermittent porphyria inheritance pattern and enzyme affected

Answer 7

dominant, hepatic PBG deaminase

Question 8

what is the likely onset of acute intermittent porphyria and what drives this?

Answer 8

puberty…sex hormones

Question 9

what two molecules will build up in acute intermittent porphyria?

Answer 9

ALA and PBG…seen in urine!

Question 10

in addition to the PBGD mutation in acute intermittent porphyria, what else is needed to see the disease?

Answer 10

induction of ALAS1 (drugs commonly)

Question 11

what happens to urine after a AIP attack?

Answer 11

will turn dark brown in sun light

Question 12

what happens to hypothalamus in AIP attack?

Answer 12

low sodium

Question 13

what are the GI symptoms in AIP attack?

Answer 13

abdominal pain without inflammatory markers, will not be bothered by touching the peritoneal cavity like woulld be with appendicitis

Question 14

what are the neuro findings in AIP attack?

Answer 14

sensory and motor issues, motor can lead to paralysis and respiratory impairment, seizures

Question 15

what happens cardiovascularly with AIP attack?

Answer 15

increased heart rate and pressure

Question 16

can smoking induce an acute attack?

Answer 16

YES

Question 17

how to diagnose AIP attack?

Answer 17

send ALA and PBG levels…if high send PBGD activity test

Question 18

two things to give in IV for AIP attack?

Answer 18

glucose…and hematin

Question 19

what is hematin and why do we give it in AIP attack?

Answer 19

old heme from RBCs…will tell enzymes to stop making the shit metabolites AKA ALA

Question 20

Porphyria cutanea tarda enzyme problem

Answer 20

uroporphyrinogen decarboxylase deficiency

Question 21

is PCT inherited or acquired?

Answer 21

both

Question 22

how males and females get PCT?

Answer 22

males drink too much booze
females take estrogen
both usually have an iron overload

Question 23

PCT associated disorders (3)

Answer 23

Hep C
hemachromatosis
alcoholism

Question 24

what is hemochromatosis

Answer 24

disorder leading to increased iron uptake and storage

Question 25

how does PCT affect the skin?

Answer 25

the uroporphyrinogen builds up and deposits in the skin, where it can be oxidized by sunlight and makes blisters that are very painful

Question 26

what two things are you at risk for with PCT?

Answer 26

cirrhosis and hepatocellular carcinoma

Question 27

treatment for PCT?

Answer 27

avoid sun and use phlebotomy to rid of excess iron

Question 28

what are the five most common places to find lead?

Answer 28

old pipes, leaded gas, leaded paint, moonshine, bullets

Question 29

what is the common mode of lead poisoning in adults and then in kids?

Answer 29

inhalation for adults and ingestion for kids

Question 30

where is most of the body lead found?

Answer 30

99% in blood...then goes into storage in bone about 95%

Question 31

what are the two enzymes that lead interferes with in heme synthesis?

Answer 31

ALAS1 and ferrochelatase

Question 32

what is seen in RBC stains after lead poisioning and why?

Answer 32

basophilic stippling...because RNA is broken down in the RBCs

Question 33

what does basophilic stippling look like?

Answer 33

coarse dark blue inclusions in an RBC

Question 34

lead toxicity symptoms

Answer 34

GI cramping microcytic anemia neuro issues like confusion/seizure

Question 35

classic lead poisoning motor problem

Answer 35

wrist and foot drop

Question 36

lead lines in lead poisoning

Answer 36

bluish lines along gum lines

Question 37

what cardiac problem can lead poisoning cause?

Answer 37

hypertension

Question 38

how to diagnose lead poisoning?

Answer 38

get venous blood lead levels, easy as that

Question 39

how to treat lead poisoning?

Answer 39

reduce exposure and chelate