Porphyrins and Hgb Flashcards
Describe porphyrins
shape?
compromised of?
joined by?
cyclic structures compromised of 4 pyrole rings joined by methine bridges
chelation of ferrous iron
to protoporphyrin ring, creates heme
Heme
binds oxygen, is a prothestetic group
Porphyrias
disorders that result from distrubance in heme synthesis
Hgb molecules
bind/deliver/release oxygen
Hgbopathies
qualitative defects
Thalassemia
quantitative defects
Porphyrins
chemical intermediate in…
pigments called?
iron is chlated into?
excess?
Chemical intermediate in synth of hgb/mygb/respiratory pirgments called cytochromes
iron is chelated into porph ring
excess compounds
Porphyrionogens
reduced…
intermediates in…
what happens w exposure to air?
reduced compounds that are intermidiate in synth of heme
oxidized on exposure to air in porphyrins
Isomers
how many for every porphyrin compound?
what types occur naturally?
4 isomers for every porphyrin compound
type I and III naturally occur
Whats special about type III isomer?
only one to form heme
T/F in some disorders the non functional type I isomer may be found in excess body fluids and tissues
true
Porphyrin properties
photo……due to….
color due to?
aqueous sol varies with…..
photoactive due to conjugation w tetrapyrole ring
dark red color due to strong absorbance (600-650nm)
aqueous sol varies w # of carboxylic acid present in substance
Uroporphyrin (Uro)
8 carb groups, most soluble in H20 excreted renally
Coprophyrin (Copro)
how many carb groups
solubility?
in?
4 carb groups, interm sol
blood and urine/feces
porphyrin groups with 2 carbs
influences?
least soluble
influences type of specimen selected to measure
Synthesis of heme
all cells contain..
primary sites?
all cells contain hemoproteins and can synth heme
BM/Liver primary site
how many molecules of heme is produced from 8 molecules of Alpha ALA?
one molecule of heme produced
What synthetic rxn require energy?
First and last three (in mitochrondria) others in cytosol
negative feedback mechanism
Control rate of heme
where?
through regulation of?
increase in pool of hepatic heme?
decreased heme?
in liver
through regulation of ALAS
increase in pool of hepatic heme decrease ALAS pool
ALAS production increase decreases heme
In bone marrow what controls rate of heme synthesis?
erythrocytes and other enzymes in pathway
Disorders of bio heme synthesis
most are?
most auto dominannt with 50% reduction in activity or affected enzymes
Enzyme defects
excess accum….
excessive accumulation/excretion of intermediate compounds that produce symptoms
Neuopsychiatric symptoms
abdominal pain, nausea, constipation
excess in early precursors in oath of heme synth (ALA/PBG)
Porph symptoms
hint (a/a)
ADP/AIP
Cutaneous
symptoms: p/b/f
excess….
c/p/e/x
increased fragility of light exposure in?
burning of light exposed skin in?
due to ?
sympt
photosensitivity, blisters, facial hair
excess porphyrin intermediates
CEP,PCT,EPP,XLPP
increased fragility of light exposure in CEP/PCT
burning of light exposed skin in EPP/XLPP
due to absorption of light of porhyrins
Neurocutaneous symptoms
excess…
h/v
excess precursors/intermediates
HCP/VP
Acute porphyrias
causes what kind of attacks?
neruophyciatirc?
neurocutaneous?
most common?
neurological/serious acute attacks
ADP/AIP - neurophychiatric
HCP/VP - neurocutaneous
AID - most common acute porphy, 80% asymptomatic
Non acute present as chronic (cutaneous)
c/p/e/x
most common?
extreme photosensitivity
CEP,PCT,EPP,XLPP
PCT most common
CEP - extreme photosensitivty
Secondary Porphyious
increased excretion of?
caused by?
examples that cause excess excretion/
inhereited?
increased excretion of urinary porphyrins
caused by another disorder/toxin interferring w heme formation
liver disease/lead posioning excess urinary porph excretion
inherited disorder of bilirubin met
Acute porphyria testing
determin what in urine?
if positive?
Determin PBG in urine
if positive - ID ALP, differentiate AIP/VP/MCP
Cutaneous porphyria testing
measured in?
increased excretion of porph pattern diagnostic for?
…..in plasma and whole blood?
measure porh in random/timed urine
increasse excretion of porph pattern in diagnostic for PCT/CEP
EPP/XLPP is plasma and whole blod
Analytical methods
wat
H
chrom
Fec
watson-schwartz assay
HPLC
Chromotographic
Fecal HPLC/flourecnese
Specimen requirements
protected from light
unpreserved urine
4 degrees - 48 hr
neg 20 for weeks
fecal frozen 20 degrees
whole blood EDTA protect from light 4 degrees
Hgb
oxy transport to tissues/CO2 back to lungs
carried to all tissues of body by erythroctes
major buffer systom of body
Hgb shape
spherical molecule
2 major parts, central oxy non protein molecule
2 glob chains, Alpha and beta
Majority of adults have what Hgb
Hgb A and A1
two alpha two beta
Hgb A2 <3% (two alpha two delta)
Hgb F (2 alpha 2 gamma)
Neonate hgb
Hgb F 2 alpha two gamma
main hgb during fetal life and 60% of hgb at birth
Hgbopathies defined
defect in structures
Thalassemias defined
defect in rate and quant of production
decreased or absent chains
alpha and beta
micro/hypo
autodom hetero
what chromosome are Alpha genes?
all others?
a genes on chrom 16
others 11
T/F in most people, the alpha gene is duplicated A1/A2 indentical alpha genes in Hgb A,A2 and F
ture
non alpha genes subject to ?
delta, beta, gamma
subject to non homologous cross over
fused/hybrid chains
hgb lepore
: what type of chains
Hgb kenya: chains?
delta beta chains
kenya: gamma beta chains
Hgbopathies divided into groups based on?
based on genetics, 4 groups
AA subsitutions
AA deletions
Elongated chains/frameshift (constant spring)
Fused/hybrid chains
Most abnormalities are?
amino acid subsittutions
2/3 hgbopathies affect Beta chains
More on thalassemia
absent/deminished?
absent/deminished synth of polypeptide chains
alpha thal: no alpha chains …etc
Synth and degradation of heme
synth occurs in?
normally requires synth in?
glob synth in
what supply?
hgb synth occures in immature rbcs/bone marrow
norm synth requires synth in mitochonrida (heme)
glob synth in cytoplasm
iron supply
Intravascular vs extravascular
I: blood vessles
E: cells/liver
Hgb S
most common in US
sickle cell HbAS
black/african population
solubility test
HGB S IS BETWEEN A AND A2
Hgb C
west africa/ghana
target cells/crystals
cellulose electrophor
moves w Hgb A2
negative tube sol
Hgb SC
most common mixed hgb B-s/B chains
no normal B chains to produce A
tube sol postive
Hgb E
Hgb D
asian microcytes somewhat unstable
D: given to varient similar to S that is tube negative, homozygous rare, found in india
Thal minor
hetero, asymptom, iron deficiencies
Thal Major
lethal before birth, complications
Alpha thal
chromosome?
hydrops fetalis?
hgb M?
silent carriers?
A thal trait?
chrom 16 4 genes
hydrops fetalis: alpha chain absense, hgb barts
Hgb M: mod heme anemia
Silent carriers: missing 1 gene
A thal trait: two gene deletion
Beta thal
caused by?
homozgous -…..causes?
Hetero?
B+
B0
caused by mutations
homozygous - major - cooley anemia, crippling in childhood, bone deformities
hetero - minor
B+ reduced chains - most common severe
B0 absent chains - dec hgb anemia
tube Solubility test
fasle neg?
false pos?
screen for sickle cells
sickling hgb means you cant read through the tube (looks turbid)
false neg due to transfusions/hgb F
false pos: whole blood vs packed rbcs
Cellulose acetate
alkaline buffer
electro mobility: AFSC
universal screening for newborn hgb op
Other tests
citric agar, Hgb A2 quant, acid elution, Hgb F quant
DNA
increase sensititivy and specificity
higher cost
prental diagn of thal major
Myoglobin
skeletal/caridac muscle
damage to muscles increase serum urine myoglobin
rapid renal clearance - increase conc = renal failure
can cause reaction like rhabdo/mI/Muscle dystrophy
