Flashcards in module 5 defective hemoglobin synthesis Deck (54):
Also known as IDA. inadequate uptake or absoprtion, blood loss. responds to iron therapy.
anemia chronic disease
defective iron metabolism iron kept in macrophages.
duodenal cytochrome b
DcytB. Reduces ferric iron to ferrous at brush border.
Divalent Metal Transport
Transports ferous iron across the apical enterocyte plasma membrane.
iron stored in enterocyte
can be as ferritin which is lost when sloughed off, or transported into across baolateral side
transports iron across basolateral side of enterocyte.
facilitates basolateral transport of iron by oxidizing to ferric form.
plasma iron protein which mediates iron exchange between tissues. negative acute phase reactant. levels decrease during acute phase response.
transferrin with no bound iron.
Total Iron binding capacity
the total amount of iron which can be bound by transferrin.
Iron delivered to transferrin comes from:
monocyte macrophage recycing. A small pefrcentage comes from absorption. Delivered to developing macrophages.
found on cells. Binds transferrin and grabs iron. Expression correlates with iron requirements.
Transferrin mechanism of action
transferrin - iron binds tfr. clusters invaginates forms endosome. Iron released, transported into cytoplasm. both proteins not degraded but recycled.
soluble transferrin receptor
Extracelluar portion of tFR released as cell matures. Increased sFTR increases as erythropoesis increases.
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.
acute phase reactant. Increases in inflammation or tissue damage. If depleted means stores are depleted.
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.
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.
Hepcidin expression modulated by:
iron stores, erythropoesis, hypoxia, inflamattion / infection.
competes with transferrin for TFR. Expressed on membrane. Free HFE when TFR bind transferrin signals to increase hepcidin expression.
coreceptor with HFE. HJV mutations decrease hepcidin expression.
TIBC < 15%
iron overload possible hemochromatosis.
Ferritin in detecting IDA
first sign low ferritin appears before low TIBC. However is an acute phase reactant.
inversely proportional body iron because receptor level increases when iron is low.
zinc incorporated into proptoporyphyrin ing in absence of iron. ZPP reflects iron over last several weeks. INcorporated in IDE stage.
labeled iron binds to transferrin, clearance from plasma measured. Can also measure incorporation into RBC (spin down). Most iron incorporated in 10-14 days.
rate plasma leaves iron
red cell utilization of iron ferrokinetics
IDA in developing countries
parasitic infection with low iron in diet.
IDA from diet alone
only in infacny adolescence, childhood.
IDA and blood loss
usually from GI tract ie lesions hemherroids etc.
Anemiain kidney disease
lack EPO. rEPO fixes. Iron cannot be mobilized quickly enough can lead to ID. Therefore give iron injection
Sprue, gastrectomy, gastritis.
Stage 1 ID
decreased serum ferrritin, increased rBC RDW.
Stage 2 ID
ZPP becomes present. % transferrin drops. Sftr increased. TIBC increased.
Stage 3 ID
microcytic microchromic. All iron tests are low.
common with IDA. ice phagia.
IDA blood picture
codocytes, elliptocytes, dacrocytes. RPI <2.
differentiate IDA from ACD
sFTR levels doubled for ID, while identical to normal people for ACD. ALso can use serum ferritin, MCV and iron saturation.
Differentiate IDA from thalassemia
ZPP levels four times higher in IDA.
ACD characterized by
by hypoferremia, decreased transferrin (decreased TIBC), increased serum ferritin, and increased iron in bone marrow macrophages. Block of release from macrophages
ACD molecular mechanism
Hepcidin blocks release from macrophages, caused by IL6 and other inflammatory cytokines. IL 6 also blocks EPO production and response.
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.
Siderblastic anemia blood work
•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.
Ferritin : hemosiderin ratio
good indicator of total body iron. When low ferritin is high, when high hemosiderin is high.
iron bound to transferrin
find a sideroblast
stain with prussian blue. iron is usually diffuse in normal blasts.
most common causes of sideroblastic anemia
lead and alcohol poisioning
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.
ferritin to hemosiderin ratio:
total body iron