RBC and Bleeding Disorders II Flashcards
hexose monophosphate shunt and glutathione metabolism
abnormal in G6PD deficiency
G6PD deficiency
RBCs cannot protect against oxidative damage
leads to hemolysis
-both intravascular and extravascular
episodic hemolysis
characteristic of G6PD deficiency
-exposures that cause oxidative stress
infections - viral hepatitis, pneumonia, typhoid
drugs - antimalarials
foods - fava beans
G6PD
glucose 6 phosphate DH
-reduces NADP to NADPH while oxidizing glucose-6P
NADPH - provides reducing equivalents for glutathione metabolism that protects against oxidative damage
-like H2O2
genetics of G6PD
X-linked trait
-males higher risk
heinz bodies
in G6PD deficiency
seen in RBCs
also bite cells
bite cells
G6PD deficiency
G6PD-
in blacks
G6PD mediterranean
protective against plasmodium falciprum malaria
greater hemolysis in this variant
only older red cells at risk for lysis
recovery phase - reticulocytosis
G6PD clinical
no spenomegaly or cholelithiasis
-bc is intermittent - no chronic hemolysis
sickle cell
beta chain point mutation codon 6
-glutamate to valine
HbA
alpha2beta2
HbA2
alpha2delta2
HbF
alpha2gamma2
beta-globin chain
one gene
alpha-globin chain
two genes
PBS of sickle cell
anisocytosis and poikilocytosis and sickled cells
sickle cell trait
heterozygote for HbS
offspring of hetero - 1/4 chance
protective effect HbS
against falciprum malaria
parasites promote sickling - get cleared rapidly - keep parasite load down
pfEMP-1
knob formation
-impaired by sickling
-knob formation on membranes
basis of cerebral malaria
sickle cell clinical
moderately severe hemolytic anemia
-Hct 20-30%
reticulocytosis, hyperbilirubinemia, and sickled cells
vaso-occlusive crisis
in sickle cell
-aka pain crisis
bones, lung, liver, brain, spleen, penis
hand-foot syndrome
painful bones in children with sickle cell
dactylitis
of bones in hands and feet
with sickle cell
acute chest syndrome
vaso-occlusive crisis in sickle cell
fever cough, chest pain, pulmonary infiltrates
blood flow - sluggish
-further hypoxemia - more sickling - bad cycle
requires prompt treatment and exchange tranfusions
priapism
in sickle cell
45% males after puberty
stroke and retinopathy to blindness
with sickle cell
depletion of NO
no vasodilation
-predisposition for stroke in sickle cell disease
sequestration crisis
in children with sickle cell
-entrapment of sickled RBCs in spleen
rapid splenic enlargement, hypovolemia, shock
requires prompt treatment and exchange tranfusions
aplastic crisis in sickle cell
with parvovirus B19 infection
cessation of erythropoiesis and anemia
chronic hypoxia with sickle cell
impaired growth and development and organ damage
hyposthenuria
sickling in kidney - damage
inability to concentrate urine
infections in sickle cell
pneumococcus pneumonia and haem influenza
because of altered splenic functions
diagnosis of sickle cell
clinical findings and presence of irreversibly sickled cells
-test - mix blood sample with metabisulfite - induces sickling
metabisulfite
for dx of sickle cell
will cause sickling in HgS patients
Hg electrophoresis
can demonstrate presence of HbS and other sickle syndromes
prenatal sickle cell diagnosis
analyze fetal DNA
-amniocentesis and chorionic biopsy