2009B12 Discuss the production and function of red blood cells.

 

List:

·         Structure

·         Production

·         Function

 

RBC structure:

Macro

·   Biconcave disc shaped cell in blood

·   8 x 2 μm

Contents

·   Large amounts of haemoglobin, carbonic anhydrase, glycolytic enzymes

·   No nucleus, no mitochondria (no anaerobic metabolism)

 

Production:

Pathway

Organs

·   Yolk sac: early embryo

·   Liver, spleen: embryo and foetus

·   Appendicular skeleton: late foetus until adolescence

·   Axial skeletal and proximal long bones: late foetus until death

Stimulants

·   Erythopoietin (Epo) most important (see below)

·   Colony stimulating factors (G-CSF, GM-CSF)

·   Stem-cell factor

·   IGF-1

·   Interleukins (esp. IL-3)

·   With maturation: organelles disappear, [Hb] increases

·   Circulating cells: 99% erythrocytes, 1% reticulocytes (reticular network of rRNA)

Epo

·   Glycoprotein hormone

·   Production: 90% renal interstitial fibroblasts, 10% liver (Fetus: mostly liver)

·   Stimulus: cellular ↓pO2

·   Mechanism: binds extracellular EpoR -> activates JAK2 cascade

·   Effect: pluripotent cell -> erythroblast

·   Degradation: liver

 

Function:

O2 carriage

·   Fe2+ in haem binds O2

·   Increases CaO2 from 2mL/100mL arterial blood (dissolved only) to 20mL/100mL

·   O2 taken up at lungs (left shift OHDC: ↓H+, ↓pCO2, ↓T, ↓2,3-DPG)

·   O2 unloaded at tissues (right shift OHDC: opposite)

·   Used for oxidative phosphorylation, ATP production

Oxyhaemoglobin dissociation curve (OHDC)

CO2 carriage

·   CO2 produced in TCA cycle

·   Diffuses into RBC

·   Converted by carbonic anhydrase and buffered

o  CO2 + H2O <-> H+ + HCO3-

o  CO2 + NH2 <-> NHCOO- + H+

o  KHb + H+ <-> HHb + K+

·   Haldane effect: deoxyHb carries more CO2 and H+ than oxyHb

o  70% due to 3.5x↑ formation of carbamino

o  30% due to pKa 6.6 -> 8.2 imidazoles

o  Hence isohydric buffering: for every 1mol O2 offloaded, 0.7mol CO2 and H+ can be added, before pH falls

o  Note arterial pH 7.44, venous only 7.36 despite extra 4mL/100mL CO2

Buffering

·   Haemoglobin is the second most important ECF buffer after bicarbonate

·   Effective in metabolic >> respiratory disorders

·   As described above

Prevent nephrotoxicity

·   Free haemoglobin damages the glomerulus

 

 

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