module 5 defective hemoglobin synthesis

Question 1

sideropenic anemia

Answer 1

Also known as IDA. inadequate uptake or absoprtion, blood loss. responds to iron therapy.

Question 2

anemia chronic disease

Answer 2

defective iron metabolism iron kept in macrophages.

Question 3

duodenal cytochrome b

Answer 3

DcytB. Reduces ferric iron to ferrous at brush border.

Question 4

Divalent Metal Transport

Answer 4

Transports ferous iron across the apical enterocyte plasma membrane.

Question 5

iron stored in enterocyte

Answer 5

can be as ferritin which is lost when sloughed off, or transported into across baolateral side

Question 6

ferroportin

Answer 6

transports iron across basolateral side of enterocyte.

Question 7

Hephaestgin

Answer 7

facilitates basolateral transport of iron by oxidizing to ferric form.

Question 8

transferrin

Answer 8

plasma iron protein which mediates iron exchange between tissues. negative acute phase reactant. levels decrease during acute phase response.

Question 9

apotransferrin

Answer 9

transferrin with no bound iron.

Question 10

Total Iron binding capacity

Answer 10

the total amount of iron which can be bound by transferrin.

Question 11

Iron delivered to transferrin comes from:

Answer 11

monocyte macrophage recycing. A small pefrcentage comes from absorption. Delivered to developing macrophages.

Question 12

Transferrin receptor

Answer 12

found on cells. Binds transferrin and grabs iron. Expression correlates with iron requirements.

Question 13

Transferrin mechanism of action

Answer 13

transferrin - iron binds tfr. clusters invaginates forms endosome. Iron released, transported into cytoplasm. both proteins not degraded but recycled.

Question 14

soluble transferrin receptor

Answer 14

Extracelluar portion of tFR released as cell matures. Increased sFTR increases as erythropoesis increases.

Question 15

Ferritin

Answer 15

acts as primary iron storage compound. Spherical 24 unit multimer composed of varying numbers of H and L chains. Found in marrow liver and spleen usually in siderosomes. Small amounts can enter plasma through lyisis.

Question 16

Ferritin (reactant)

Answer 16

acute phase reactant. Increases in inflammation or tissue damage. If depleted means stores are depleted.

Question 17

hemosiderin

Answer 17

non specific iron carbs, lipid protein. Found usually in macrophages. Formed after lysosome degradation of ferritin at very high iron levels. Released slowly not readily available for functions.

Question 18

Hepcidin

Answer 18

synthesized in liver. Master iron regulator. decreases iron absorption into the body by binding to and inducing degradation of ferroportin. Also blocks export from macrophages.

Question 19

Hepcidin expression modulated by:

Answer 19

iron stores, erythropoesis, hypoxia, inflamattion / infection.

Question 20

Hepcidin infection

Answer 20

decreased.

Question 21

HFE

Answer 21

competes with transferrin for TFR. Expressed on membrane. Free HFE when TFR bind transferrin signals to increase hepcidin expression.

Question 22

HJV

Answer 22

coreceptor with HFE. HJV mutations decrease hepcidin expression.

Question 23

TIBC < 15%

Answer 23

possible ID

Question 24

TIBC >50%

Answer 24

iron overload possible hemochromatosis.

Question 25

Ferritin in detecting IDA

Answer 25

first sign low ferritin appears before low TIBC. However is an acute phase reactant.

Question 26

SfTR

Answer 26

inversely proportional body iron because receptor level increases when iron is low.

Question 27

ZPP

Answer 27

zinc incorporated into proptoporyphyrin ing in absence of iron. ZPP reflects iron over last several weeks. INcorporated in IDE stage.

Question 28

ferrokientics

Answer 28

labeled iron binds to transferrin, clearance from plasma measured. Can also measure incorporation into RBC (spin down). Most iron incorporated in 10-14 days.

Question 29

PIT

Answer 29

rate plasma leaves iron

Question 30

RCU

Answer 30

red cell utilization of iron ferrokinetics

Question 31

IDA in developing countries

Answer 31

parasitic infection with low iron in diet.

Question 32

IDA from diet alone

Answer 32

only in infacny adolescence, childhood.

Question 33

IDA and blood loss

Answer 33

usually from GI tract ie lesions hemherroids etc.

Question 34

Anemiain kidney disease

Answer 34

lack EPO. rEPO fixes. Iron cannot be mobilized quickly enough can lead to ID. Therefore give iron injection

Question 35

IDA malabsorption

Answer 35

Sprue, gastrectomy, gastritis.

Question 36

Stage 1 ID

Answer 36

decreased serum ferrritin, increased rBC RDW.

Question 37

Stage 2 ID

Answer 37

ZPP becomes present. % transferrin drops. Sftr increased. TIBC increased.

Question 38

Stage 3 ID

Answer 38

microcytic microchromic. All iron tests are low.

Question 39

Pica

Answer 39

common with IDA. ice phagia.

Question 40

IDA blood picture

Answer 40

codocytes, elliptocytes, dacrocytes. RPI <2.

Question 41

differentiate IDA from ACD

Answer 41

sFTR levels doubled for ID, while identical to normal people for ACD. ALso can use serum ferritin, MCV and iron saturation.

Question 42

Differentiate IDA from thalassemia

Answer 42

ZPP levels four times higher in IDA.

Question 43

ACD characterized by

Answer 43

by hypoferremia, decreased transferrin (decreased TIBC), increased serum ferritin, and increased iron in bone marrow macrophages. Block of release from macrophages

Question 44

ACD molecular mechanism

Answer 44

Hepcidin blocks release from macrophages, caused by IL6 and other inflammatory cytokines. IL 6 also blocks EPO production and response.

Question 45

Sideroblastic anemia

Answer 45

mutations in ALAS, first heme pathway protein. by (1) an increase in total body iron, (2) the presence of ring sideroblasts in the bone marrow, and (3) hypochromic anemia.

Question 46

Siderblastic anemia blood work

Answer 46

•Dual population of hypochromic and normochromic erythrocytes •Pappenheimer bodies in erythrocytes •normal or increased platelets •Increased serum iron, serum ferritin, and percentage of saturation •Ring sideroblasts in the bone marrow Hyperplastic BM RPI < 2.

Question 47

Ferritin : hemosiderin ratio

Answer 47

good indicator of total body iron. When low ferritin is high, when high hemosiderin is high.

Question 48

serum iron

Answer 48

iron bound to transferrin

Question 49

find a sideroblast

Answer 49

stain with prussian blue. iron is usually diffuse in normal blasts.

Question 50

most common causes of sideroblastic anemia

Answer 50

lead and alcohol poisioning

Question 51

HBS pathophysiology

Answer 51

GLU-> Val mutation on surface causes less polar and less soluble in deoxy state. Reversible on oxygenation. Delays means most blood cells do not sickle, but sickle in spleen kidney and other hypoxic acidic environments.

Question 52

ferritin to hemosiderin ratio:

Answer 52

total body iron

Question 53

IDE stage

Answer 53

ZPP incorporated.

Question 54

most common causes acquired SA

Answer 54

alcohol and lead poisoning.