resp: anemias of increased RBC DESTRUCTION; membrane and enzymatic defects

selective permeability and deformity

1. outer lipid bilayer w/ embedded proteins
2. underlying membrane proteinaceous skeleton

serves as selective barrier, allowing only necessary molecules entry and exit

provides RBC its characteristic shape, structure, and deformability

differences in shape and deformability -/+ permeability to certain molecules

1. variable clinical presenations and severities
2. if symptomatic include: anemia, jaundice, and splenomegaly
3. hemolysis is extravascular (in the spleen)

AD

ankyrin
spectrin
band 3
protein 4.2
-vertical
-disconnect the lipid bilayer from underlying cytokeletal proteins

anemia
jaundice
splenomegaly

-spherocytes on peripheral smear
-inc #s of reticulocytes
-unconjugated bilirubin
-dec haptoglobin
-inc osmotic fragility

splenectomy

AD

spectrin
protein 4.1
-horizontal
-inability of spectrin dimers to form tetramers and oligomers

variable
asymptomatic
significant hemolytic anemia: anemia, jaundice, splenomegaly

-unconjugated hyperbilirubinemia
-dec haptoglobin
-

most do not require tx
splenectomy for some

AR

spectrin
-impair conversion of dimers into tetramers and oligomers
-partially deficient in spectrin due to dec synthesis -/+ increased degradation

present in neonatal period with hemolytic anemia and jaundice

-RBC with marked thermal sensitivity
-bizarre shaped and microcytic cells

transfusion and phototherapy

AD

stomatin
-intergral membrance protein is dec or absent
-abnormal RBC membrane permeability which leads to either hydrocytosis (inc MCV) or xenocytosis (dec MCV)

failure of Na/K pumps leads to elevated erythrocytoic Na content and cell water

lose K+, but mechanism is unknown

hydro: macrocytic and inc osmotic fragility

xeno: dec osmotic fragility

mouth-shaped area of central pallor

variable severities of permeability defects, stomatin deficiency, hemolysis, anemia, and # of stomatocytes
-marked predisposition to thrombotic episodes after splenectome (inc erythrocyte-endothelial cell adhesion)

underlying disorders of internal RBC metabolism

-increased RBC destruction and hemolytic anemia

1. anaerobic: EMP, glycolysis
2. aerobic: PPP

only 2 molecules of ATP
10% of RBC glucose

-supply reducing potential to the cell, by generating NADPH
-NADPH: generating glutathione, which reduces oxidized sulfhydrl groups in Hb

EMP/glycolysis

PPP

AR
most are homozygous or double hetero for 2 mutant genes

reduced activity (not absence)
-marked reduction in ATP production which leads to impairment of Na/K ATPase pump

-K is lost, along with water - cell shrinkage and distortion of shape; distorted are destroyed prematurely

inc production of 2,3-DPG which increases 2-3 fold in PK pts
-increased capability to release oxygen to the tissues, inc exercise capacity, dec symptoms

variable
-requiring transfusions
-asymptomatic
anemia, splenomegaly, jaundice, gallstones

no prominent morphological features
-elevated unconj bili
-dec haptoglobin

X-linked recessive

G6PD is important for NADPH production which regenerates reduced glutathione which is necessary to protect RBCs from oxidative stress (detoxifies H2O2 and free radicals, protecting enzymes and Hb from oxidation)

-if deficient: Hb is denatured and membrane thiols are oxidized forming heinz bodies
-heinz bodies attach to membrane sulfhydryls and induce cell rigidity

-heinz bodies
-hemoglobinuria
-dec haptoglobin
-bite cells

hemogloinuria
jaundice

manifests with a sudden onset of acute hemolysis 24-48 hours after ingestion of fava beans (in small % of G6PD pts)

hemoglobinuria

supportive
transfusion