Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
39 Cards in this Set
- Front
- Back
|
examples of qualitative Hbopathies
|
structural: w/ Hbs with an altered amino acid sequence that results in deranged function or altered chemical of physical properties
-Hb S, Hb C, Hb E, Hb lepore, Hb Constant Spring |
|
|
examples of quantitative Hbopathies
|
thalassemias result from defective production of globin chains
alpha beta |
|
|
Hb S:
mutation |
missense
A->T for amino acid 6 glutamic acid -> valine -S variant B globin instead of nL B globin |
|
|
Hb S:
charge effect |
less negative (+1)
|
|
|
Hb S:
properties |
insoluble
aggregates into densely packed polymers - reversible upon oxygenation sickling is due to polymer-mediated distortion of the RBCs rare in Hb AS, common in Hb SS |
|
|
Hb AS:
clinical findings |
asymptomatic
-increased renal infections -blood in urine -sickling at high altitudes or low O2 conditions -protective against p. falciparum ratio: Hb A:Hb S 60-40 |
|
|
Hb SS:
properties |
100% Hb S
-sickling - low O2 cause polymerization and RBC shape distortion -viscosity increases, flow slows -normochromic, normocytic chronic anemia with acute hemolytic crises -rigid, cause obstruction |
|
|
Hb SS:
clinical findings |
great diversity
-hand and foot dactylitis -splenic sequestration syndrome -chronic leg ulceration |
|
|
Hb SS:
effect of concominant diseases |
-with Hb F: overall protection from pain and mortality
-w/ alpha thal: improved RBC hydration and survival |
|
|
Hb SS:
pathophys of sickle cell dz |
vasoocclusion
-adhesion, inflammation, deformability |
|
|
Hb SS:
lab testing |
review of PB smear and sickle solubility screening test
|
|
|
sickle solubility screening test
|
-lyse RBS to release Hb
-add reducing agent (sodium dithionite) -deoxy Hb S is insoluble and precipitates within 15 min -if Hb S: cloudy -nonsickling: clear |
|
|
Hb C:
mutation |
B-globin variant with a substitution of lysine for glutamic acid at amino acid 6
|
|
|
charge change in Hb C
|
increase of +2
|
|
|
lab findings in Hb C
|
-mild microcytic
-hypochromic anemia -target cells -folded cells -inc reticulocytes -no Hb A on electrophoresis -tetragonal CRYSTALS |
|
|
clinical findings in Hb C
|
hetero: asymptomatic
protection against p falciparum |
|
|
Hb SC genetics
|
1 beta - HbS mutation
1 beta - HbC mutation most common compound heterozygote Hbopathy |
|
|
clinical/lab findings in Hb SC
|
sickle cell crises
crystals in splenectomized pts |
|
|
thalasemmias arise due to...
syndromes arise due to... |
defective production of globin chains
-inadequate Hb synthesis and unbalanced accumulation of unaffected globin subunits |
|
|
B-thalassemias:
genetics |
hetero group causes by different mutations on chrom 11 in beta-globin gene expression
-point mutations |
|
|
B-thalassemias MAJOR:
cause |
result of inheriting 2 B-thalassemic alleles on chrom 11
|
|
|
B-thalassemias:
symptoms |
manifest when Hb F dec
-expansion of BM -thinning of cortex of bone "hair on end" -frontal bossing -prominent maxilla -pathologic long bone fractures -delayed growth -hepatosplenomegaly -jaundice |
|
|
B-thalassemia MINOR:
characterisitics |
(asymptomatic)
dec production by one B gene -mild microcytic, hypochromic anemia -inc RBCs and target cells |
|
|
B-thalassemias INTERMEDIA:
characterisitcs |
one severe or two mild mutations
-moderate anemia -degree of severity based on mutation |
|
|
alpha-thalassemia:
genetics |
deletion of one or more alpha globin genes on chrom 16
|
|
|
alpha-thalassemia:
molecular defects |
loss of alpha gene
-B-globins exceed alphas and form tetramers (B4s) -soluble but precipitate with age making RBCs less deformable -anemia due to shortened lifespan -one gene deletion: silen carrier -two: thal minor 3: thal major 4: fatal - alpha-Bart |
|
|
alpha-thalassemia major:
aka? characteristics |
3 gene deletion
aka Hb H -mild to moderate chronic hemolytic anemia -low Hb -inc retics -splenomegaly -erythroid hyperplasia in BM |
|
|
alpha-thalassemia minor:
characteristics |
2 gene deletion
-mild microctyic, hypochromic anemia |
|
|
Hb with thalassemia phenotype
|
HbE
HbCS HbLepore |
|
|
Hb E:
characteristics |
B chain variant
lysince for glutamic acid -dec amounts of variant are made due to mutations effect on splice site -HbE: resembles mild B-thalassemia; asymptomatic |
|
|
HbEE
|
more microcytosis but still asymptomatic
|
|
|
combination of Hb E and B-thal
|
thal intermedia or major
|
|
|
Hb CS:
characteristics |
alpha globin variant that eliminates a stop codon, producing an abnormally long alpha globin
-electrophoresis: unstable (faint) slow moving band -most common in SE Asia (50% SE Asians with alpha-thal co-inherit HbCS) |
|
|
Hb Lepore:
characteristics |
B globin structure variant which is also a thalassemia
-delta/Beta hybrid -aberrant crossover during meiosis with unequal distribution of genes -mediterranean -made in dec amounts therefore alpha is in excess forming tetramers therrefore destroyed prematurely -heteros: asymp -homos: severe microcytic, hypochromic anemia like B-thal major |
|
|
Hb F persistence:
2 types |
pancellular: uniform distribution and high levels of HbF in all RBCs
heterocellular: inherited increases in the number of F cells |
|
|
2 types of pancellular Hb F persistence
|
-deletional forms that remove beta/delta and bring enhancer sequences close to delta genes
-nondeletional caused by mutations in promoter regions of gamma genes (outside of delta/beta gene cluster) |
|
|
kleihauer-betke staining
|
Hb F will stain dark pink b/c its more alkali-resistant than Hb A
Hb A will appear as pale pink ghosts |
|
|
Hbopathies vs thalassemias:
Hb |
Hb:
-qualitative -altered AA sequence -deranged function -altered chemical/physical properties -RESULT: abnL clumping, vasoconstriction |
|
|
Hbopathies vs thalassemias:
thalassemias |
thals:
-quantitative -defective production of globin chains RESULT: dec production therefore inc of other (tetramers), dec Hb |
