Unit 3 - Formative 8 D1

Front 1

Hemoglobinemia

Back 1

Increased Hb levels in blood plasma

Front 2

Hemoglobininuria

Back 2

Increased Hb levels in urine

Front 3

Why is there a decrease in serum haptoglobin levels in intravascular hemolytic anemia?

Back 3

In intravascular hemolysis free hemoglobin will be released into circulation and hence haptoglobin will bind the Hb. This causes a decline in Hp levels.

Front 4

Extravascular Hemolytic Anemia

Back 4

Splenic marcophages phagocytose RBCs and thus haptoglobin levels are normal

Front 5

Where is Heme degraded in intravascular hemolytic anemia?

Back 5

Hepatocytes; degraded into Fe and porphyrin

Front 6

Where is Heme degraded in extravascular hemolyic anemia?

Back 6

Splenic macrophages; degraded into heme and porphyrin

Front 7

Hereditary Spherocytosis

Back 7

AD; RBC cytoskeletal membrane protein defects render erythrocytes spheroidal, less deformable, and vulnurable to splenic sequestration and destruction

Front 8

Hereditary Spherocytosis Pathophysiology

Back 8

Defects in membrane skeletal proteins lead to defective SPECTRIN; this causes RBC to become unstable and they assume a spheroidal shape (spherocytosis)

Front 9

Glucose-6-Phosphate Dehydrogenase Deficiency

Back 9

Normally reduces glutatihone (which protects RBC from oxidative injury); if G6PD is deficient, oxidant stresses induce hemoglobin denaturation (Heinz bodies)

Front 10

Heinz Bodies

Back 10

Precipiated denatured hemoglobin, which occurs due to oxidant stress and lack of reduced glutathione in G6PD deficiency

Front 11

Are ROS generated by ferrous or ferric iron?

Back 11

Ferric

Front 12

Pyruvate Kinase Deficiency

Back 12

AR; defect in pyruvate kinase -> decreased ATP production -> rigid RBC -> hemolysis

2,3 BPG accumulation (which is trying to offset the effects of the anemia)

The final step of energy generating stage of glycolysis is blocked

Front 13

What is the mutatoin producing sickle cell anemia?

Back 13

HbS mutation is a single amin oacid replacement in Beta chain (substitition of normal glutamic acid with VALINE)

Front 14

What is the pathogenesis of sickle cell anemia?

Back 14

Deoxygenated HbS polymerizes; low 02 or dehydration precipitates sickling (since there's more contact)

Front 15

What is the evolutionary function of sickle cell anemia?

Back 15

Protective against malaria in heterozygotes

Front 16

Why are newborns initially asymptomatic with sickle cell anemia?

Back 16

Increased levels of HbF (until about 6 months, when HbS ramps up in long bones)

Front 17

What are some complications of sickle cell anemia?

Back 17

Aplastic crisis (due to B19 infection)
Autosplenectomy (repeated episodes of vaso-occlusion have caused progressive scarring and shrinkage of spleen)

Front 18

What kind of variables affect sickling of cells?

Back 18

Severity of disease is enhanced by any variable that reduces the affinity of HbS for oxygen (low oxygen, decreased pH, increased pC02, dehydration, increased 2,3 BPG)

Front 19

Why can you use electrophoresis to diagnose hemoglobinopathies?

Back 19

Because point mutations in globin chains alter the properties of hemoglobins

Front 20

How would HbS compare to HbA on an electrophoretic gel?

Back 20

HbA would be farther along the gel towards the anode then HbS

Front 21

A-Thalassemia Mutatoin

Back 21

Defect; alpha globin gene mutation -> decreased alpha-globin synthesis

Front 22

Newborns with Alpha-Thalassemia

Back 22

Excess unpaired gamma-globin forms gamma4 tetramers (Hb Barts); each tetramer can't deliver oxygen to tissues; leads to hydrops fetalis

Front 23

Hydros Fetalis

Back 23

4 bad alpha-globin genes results in accumulation of fluid in fetal compartments

Front 24

B-Thalassemia Mutation

Back 24

Point mutations in splicing sites and promoter regions for B-globin

Front 25

B-thalassemia Minor

Back 25

Heterozygote; B chain is UNDERPRODUCED; usually asymptomatic

Front 26

B-Thalaseemia Major

Back 26

Homozyote; B chain is absent -> severe anemia requiring blood transfusion (secondary hemochromatosis)

Marrow expansion ("crew cut" on skull xray) -> skeletal deformities. Chipmunk facies

Front 27

How can you differentiate between folate and B12 megaloblastic anemias?

Back 27

In folate deficiency, the gastric atrophy and neurologic changes associated with VB12 deficiency do not occur.

Front 28

Macrocytic Anemia

Back 28

Impaired DNA synthesis -> maturation of nucleus delayed relative to maturation of cytoplasm
(since RNA synthesis is not and cytoplasmic protein development proceeds at normal pace)

Front 29

Iron Deficiency Anemia

Back 29

Deficient heme synthesis due to inadequate iron supply; protophoryin IX accumulates

Front 30

Sideroblastic Anemia

Back 30

Sufficient iron supply but insufficient heme synthesis

Front 31

Basis for microcytic hypochromatic RBC morphology in iron deficiency anemia and sideroblastic anemia

Back 31

Heme is required to inactivate heme kinase; in the absence of heme, active heme kinase phosphorylates and inactivates EIF2 thereby blocking protein synthesis -> erythroid precursor cells remain small in size (microcytic); the absence of heme results in a hypochromic morphology

Thus iron deficiency or sideroblastic anemias are microcytic, hypochromic anemias