Sickle Cell Anemia

Question 1

Biomarkers identified for severity

Answer 1

Decreased Apolipoprotein A-1, Increased micro RNA mir144

Question 2

N-acetylcysteine (NAC)

Answer 2

potential therapy drug

Reduces dense cells, increases intracellular GSH, decreases ISC levels, decreases acute VOC episodes

Question 3

Causes of vaso-oclusion

Answer 3

Altered RBCs (irreversible sickle cells), altered WBC, endothelial cells in blood vessels, plasma factors (adhesion proteins)

Question 4

Formation of ISC is caused by

Answer 4

oxidative stress, cysteine modification

Question 5

Locking of Sickle Shape is caused by

Answer 5

decreased alpha-spectrin ubiquitination, and formation of beta-actin disulfide bridge

Question 6

Dense cells are caused by

Answer 6

decreased GSH which results in increased oxygen radicals and oxidative damage to Gardos Channel which results in increase loss of K+ and cell dehydration

Question 7

What increases rate/amount of sickling

Answer 7

fever, acidosis, dehydration

Question 8

sickle beta 0 thalassemia

Answer 8

no hemoglobin A, severe anemia

Question 9

sickle beta + thalassemia

Answer 9

some hemoglobin A, mild anemia

Question 10

SC

Answer 10

C is defect of lysine, mild anemia

Question 11

Splenic vaso oclusion results in

Answer 11

an inhibition of bacterial clearance. Encapsulated bacteria require splenic clearance.

Question 12

Sickle shape is result of

Answer 12

formation of linear chains of polymerized hemoglobin S

Question 13

Sickle Cell Disease Clinical Effects

Answer 13

Bacterial Sepsis, Painful Vaso-occlusive episode, thrombotic stroke, acute chest syndrome, acute splenic sequestration crisis

Question 14

Acute Chest Syndrome

Answer 14

diffuse/bacterial loss of airspace

Question 15

Acute Splenic Sequestration

Answer 15

Acute vaso oclusion leads to sudden enlargement of spleen

Question 16

Cure for Sickle Cell

Answer 16

Bone Marrow Transplant

Question 17

Therapies for Sickle Cell

Answer 17

Hydration, Narcotics, Oxygenation, RBC transfusions, Hydroxyurea

Question 18

oxidative stress

Answer 18

when the activity of antioxidants is too low to compensate for the production of ROS (reactive oxygen species)

Question 19

glutathione (GSH)

Answer 19

antioxidant that prevents damage by ROS. inversely proportional to cell density. highest density RBCs have low levels of GSH.

Question 20

multiple adhesion molecules

Answer 20

cause interactions between RBC, leukocytes, and endothelial cells leading to vasooclusion

ex. PSGL-1 (P-selectin glycoprotein ligand 1), ESL-1 (E-selectin ligand 1)

Question 21

xanthine oxidase

Answer 21

enzyme that upon reperfusion converts oxygen into superoxide radical

Question 22

ischemia-reperfusion

Answer 22

what happens when clogging of RBCs and leukocytes via attachment to the blood vessel wall leads to vassooclusion which leads to ischemia which leads to a burst of ROS production when blood flow is restored.

Question 23

production of ROS leads to

Answer 23

NFkB activation, inflammation, release of inflammatory cytokines, activation of leukocytes, increased expression of adhesion molecules, further vascular plugging, decreased NO availability, etc.

Question 24

Cysteine Modification

Answer 24

occurs when oxidative stress causes sulfenic acid to be further oxided to sulfinic acid or sulfonic acid which are both irreversible reactions.

Question 25

oxidative damage to scramblase

Answer 25

results in loss of phosphatidyl serine asymmetry across RBC lipid bilayer. You end up with patches of negatively charged head group on the outer leaflet which associates with clotting factors.

Question 26

sickle cell severity

Answer 26

correlated to percentage of dense cells and irreversible sickle cells