red cell metabolism Flashcards
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
biliverdin production reaction
haem + 3O2 + NADPH –(haem ogygenase)–> biliverdin + Fe2+ + CO + H2O + NADP+
bilirubin production reaction
biliverdin –(NADPH + Biliverdin reductase (catalyst providing H+))–> bilirubin
central methene bridge is reduced to methane
what is gilbert’s syndrome
an inherited (genetic) liver disorder that affects the body’s ability to process bilirubin -> short episodes of jaundice, where the skin and whites of the eyes turn yellow
what molecule does bilirubin become conjugated to
glucuronic acid x2
what is kernicterus
high levels of unconjugated bilirubin in a baby’s blood which causes it to be deposited in the brain and cause defects
what do bacteria break conjugated bilirubin into in the gut
Stercobilinogen
2 causes of dark urine
obstruction (gall stone disease); pancreatic cancer
where is stercobilinogen reuptaken and in what from
in the small bowel as urobilinogen
causes of haemolytic jaundice (2)
- alloimmunization (maternal–fetal blood type incompatibility);
- congenital disorders of red blood cells, such as hereditary spherocytosis and G6PD (glucose-6-phosphate dehydrogenase)
deficiency;
haemolytic jaundice pathophys
increased red blood cell destruction leading to more bilirubin present -> more being conjugated and excreted than normal but the system is overwhelmed and so an abnormally large amount of unconjugated bilirubin is found in the blood
what happens if hepatocytes cannot take up bilirubin from the blood
accumulation of unconjugated bilirubin
what can increase conjugated bilirubin levels in the blood
- defective secretion of conjugated bilirubin by hepatocytes (=> retuns to the blood);
- obstruction in the biliary network;
what can painless jaundice be indicative of
pancreatic cancer
obstructive liver disease test results (urine, faeces, bilirubin, urobilogen)
urine - dark;
faeces - pale;
bilirubin - elevated (conjugated);
urobilogen - negative
hepatic liver disease test results (urine, faeces, bilirubin, urobilogen)
urine - normal
faeces - normal
bilirubin - elevated
urobilogen - elevated/normal
haemolytic liver disease test results (urine, faeces, bilirubin, urobilogen)
urine - normal
faeces - normal
bilirubin - elevated (unconjugated)
urobiligen elevate
what can trigger haemolytic anaemia in those with G6DP deficiency
malaria prophylaxis e.g. primaquine
what are the 6 blood transfusion reactions
- Febrile non haemolytic transfusion - most common, Occurs within 4h due to accumulated inflammatory cytokines in donor blood;
- haemolytic transfusion reaction (delayed and acute) - due to mismatch of donor antigens (ABO/Rh) and recipient antibodies (acute - minor antigens in delayed);
- allergic - anaphylaxis (non-IgE), due to antibodies against proteins on donor plts, leukocytes or in plasma;
- Transfusion related acute lung injury (TRALI) - Leading cause of transfusion related death, Resembles ARDS, usually occurs due to leukoagglutinins in plasma targeting recipient leucocyte antigens on neutrophils sequestered in the lungs, resulting in an immune reaction;
- Transfusion associated cardiac overload (TACO) - Volume overload from transfusion;
- Transfusion associated graft versus host disease - due to donor leukocytes attacking immunosuppressed recipient
how is febrile non haemolytic transfusion reaction treated
stop transfusion, give APAP (automatic positive airway pressure) and H2 blockers, meperidine
how is haemolytic transfusion reaction
acute - stopping transfusion, notifying blood bank, testing for haemolysis and DIC, Aggressive IV hydration needed;
delayed - Treatment with notification of blood bank, repeat testing for minor antigens (DAT, type and screen ect)
how is allergic transfusion reaction treated
adrenaline, H2 blockers and steroids
how is TRALI treated
ventilatory support and use of platelets from male donors in future
how is TACO treated
diuretics, give minimum units recquired
how can graft vs host reaction be prevented
irradiated and leukocyte reduced blood in immunosuppressed recipients
