red cell metabolism Flashcards
(48 cards)
avg RBC diameter and its clinical significance
7-8 μm - important to know as if transfusion is given via a cannula with a smaller bore than this (pink) the RBCs will lyse instead of being transfused through
what can occur with high K+ levels
complete systolic arrest -> massive MI
6 functions of the RBC
- oxygen carriage and delivery;
- energy release;
- deoxygenated promote blood flow;
- immune response (free radical release);
- intra-cellular buffer;
- K+ homeostasis
where does haem synthesis occur
- mitochrondria (precursor found here);
- cytoplasm (many intermediate steps);
- mitochrondria (final haem producing step)
why does a build up of the intermediate ring molecules in haem synthesis lead to damage
they easily fluoresce (drop down to lower energy state, releasing energy into cell) which causes damage
what is the rate limiting reaction for Haem synthesis (important!!)
the formation of ALA;
condensation of succinyl CoA + glycine -> enzyme bound alpha-amino-beta-ketoadipate -> decarboxylation to delta-aminolevulinate (ALA)
what disease can be causes by a build up of ALA
ALAD porphyria
porphobilinogen synthesis (from ALA)
ALA –(ALA dehydratase)–> phorphobilinogen (a pyrrole)
what does ALA dehydratase contain and why is this important
it is a -SH containing enzyme -> easily inhibited by trace heavy metals binding e.g. lead
what does uroporphyrinogen I synthase catalyse
prophobilinogen –(Deamination)–> linear tetrapyrrole with alternating acetic acid and pronoic acid groups
what molecule is transported from the cytoplasm to the mitochondria for the final steps of haem synthesis
coproporphyrinogen III
what does ferrochelatase catalyse
protoporphyrin IX – (Fe2+, absorbic acid, cysteine)–> Haem
what can inhibit ferrochelatase
lead
what is porphyria
a rare autosomal dominant inherited disorder characterised by a partial deficiency of porphobilinogen deaminase, which leads to the accumulation of porphyrin precursors and porphyrins in the body
4 porphyria types and their symptoms
- acute attacks: unexplained abdominal pain; nausea; vomiting; constipation; neuropsychiatic conditions
- erosive photodermatosis: blisters, skin fragility, hypertrichosis
- acute painful photosensitivity: burning seensations after sun exposure
- neonatal prophyrias: neonatal issues, haemolytic anaemia, bullae, severe neruological defects
4 porphyria types and what findings are seen in them (urine, plasma etc.)
acute attacks: PBG + AL in urine;
erosive photodermatosis: plasma fluorescence emission peak;
acute painful photosensitivity: protoporphyrin IX in erythrocytes;
PGB, ALA + porphyrins in urine
what are the major enzymes involved in porphyria (important!) -3
Urine Porphobilinogen (PBG); delta-aminolevulinic acid (ALA) dehydratase (leads to accumulation of ALA); ferrochelatase (leads to protopophyrin IX accumulation)
what investigation should be done if pt presents with acute neurovisceral features (w/wo skin lesions)
quantify PBG and ALA in urine
investigations for presentation with sun-induced urticaria or erythema
measure erythrocyte protoporphyrin concentration
investigation for presentation of active skin lesions (erosions/bullae)
measure plasma/urine porphyrin profile
why does unconjugated bilirubin accumulate (compared to conjugated)
unconjugated bilirubin is lipid soluble and so cannot be easily dissolved and excreted -> conjugated can be
blockages where results in bilirubin retention
bile duct
what is seen with bilirubin blockage (stools)
white stools
what are the first 3 substrates in the Hb breakdown reaction
haem; 3O2; NADPH
