Heme II Unit #1.2

Hemoglobinopathies

genetically determined abnormality of structure or synth of hgb

Qualitative

structural defect of globin chain

Quantitative

defect in globin synth

Hgb F

expressed during fetal development. variants unlikely to be detected after 3 - 6 mo

HgbA2

minor hgb (<4% in adults). unlikely to cause complications because so low

Alpha Gene

has 2 copies on each of the number 16 chromosome, less likely to cause complications

Beta Chain

single copy on each of the number 11 chromosome. associated with complications when mutated

Hemoglobin Variants

common variants involve a single AA sub or deletion

Hemoglbin Alterations

function, stability, or solubility

CBC

tests for anemia, RDW, and RBC indicies

Hgb Variant Testing

high-performance liquid chromatography, electrophoresis, isoelectric focusing

Hgb Electrophoresis

charge depends on AA sequence and pH surrounding medium. subs affect charge

Solubility Tests

normal hgb stays dissolved in cytoplasm

Heat precipitation tests

variant denatures, precipitates = heinz bodies

Molecular Hgb Testing

PCR and restriction fragment length polymorphism

Altered Solubility

a nonpolar AA replaces a polar AA near surface

Altered Function

Can occur as iron oxidation or altered allosteric behavior

Iron oxidation

sub stabilizes heme iron in ferric state, which cant bind oxygen. Methemoglobin

Altered allosteric behavior

sub locks hgb into relaxed or tense state, increasing or decreasing oxygen affinity

Altered Stability

reduced stability of Hgb tetramer results in unstable Hgb disrupting hydrogen bonds and hydrophobic interactions, denatures, aggregates, and precipiates = heinz bodies

Sickle Cell Structure

Glu turns to Val (non-polar) in 6th position of beta chain. Solubility in deoxygenated state is decreased causing polymerization and rigid aggregates

Factors that promote sickling

hypoxia, acidosis, hypertonicity, hot temperatures

Repeated Sickling Affects

loss of K+ and water from cell, increased MCHC, increased cytoplasmic viscosity, decreased cell deformability

Polymerization Begins

when oxygen saturation is less than 85% with Hb S

Polymerization completes

when oxygen saturation is at 38% with Hb S