Diseases of Iron Metabolism Flashcards
1
Q
iron metabolism disorders
A
defect in hemoglobin synthesis due to a deficiency of iron or abnormal utilization of iron
2
Q
microcytic hypochromic anemia
A
red cell disorders
3
Q
types of iron metabolism disorders
A
microcytic hypochromic anemias
iron overload
4
Q
types of microcytic hypochromic anemias
A
iron deficiency anemia
anemia of chronic disease
sideroblastic anemia
5
Q
type of iron overload
A
hemochromatosis
6
Q
causes of iron deficiency
A
insufficient dietary intake of iron
absorption is impaired
increased loss of iron through bleeding
7
Q
causes of iron overload
A
absorption abnormally increases
individual receives multiple transfusions
individual receives iron injections
8
Q
disturbances in heme & globin synthesis can cause
A
defective hb production
9
Q
types of disturbances in heme synthesis
A
deficient iron
defective iron metabolism
defect in porphyrin synthesis
10
Q
iron is found associated with or as
A
functional iron
transport
storage
11
Q
types of functional iron
A
hemoglobin
myoglobin
12
Q
type of transport iron
A
transferrin
13
Q
types of storage iron
A
hemosiderin
ferritin
14
Q
total iron concentration in the body
A
40-50 mg of iron/kg of body weight
15
Q
iron homeostasis depends on balance of
A
absorption of iron
total body requirements
16
Q
two forms of dietary iron
A
nonheme iron (ferric, fe3+) heme iron (ferrous, fe2+)
17
Q
where is nonheme iron found
A
vegetables, whole grains
18
Q
where is heme iron found
A
red meats
19
Q
nonheme iron
A
ferric, fe3+
20
Q
heme iron
A
ferrous, fe2+
21
Q
how is nonheme iron different from heme iron
A
nonheme is not easily absorbed
gastric acid solubilizes the iron complex
reduces ferric iron to ferrous form
low pH allows transport of iron across the enterocyte membrane
22
Q
where is ferrous iron form absorbed
A
through the mucosal cells (enterocytes) of the intestine
23
Q
how is ferrous iron absorbed
A
fe2+ is oxidized to fe3+ for binding to transferrin
transferrin distributes to body tissues or for storage
absorption increased when erythropoiesis increased & iron stores depeleted
24
Q
where is ferric iron form absorbed
A
enters through the blood stream
25
transferrin
plasma iron transport protein mediates iron exchange between tissues
26
what is transferrin made of
a single polypeptide
two homologous lobes
two atoms of ferric iron can bind to one transferrin molecule
27
what do the two atoms of ferric iron bound to one transferrin molecule do
maintains iron in soluble form
28
what does transferrin do
assists iron delivery to erythroblasts in bone marrow by plasma circulation
29
transferrin receptor 1 (TfR1)
expressed on virtually all cells
| one molecule of transferrin binds to TfR1
30
transferrin/TfR1 complex
enters cell
iron is released
TfR1 available for recycling
31
iron not used for erythropoiesis
stored in the reticuloendothelial cells of BM, liver, spleen, as ferritin or hemosiderin
32
ferritin
major form of iron storage
stores up to 4500 molecules of Fe3+
primary storage compound for iron
readily available for erythropoiesis
33
ferritin stores what type of iron
nonheme - ferric, fe3+
34
hemosiderin
found in macrophages
aggregate of iron, carbohydrate, lipid, protein
iron from hemosiderin is released slowly - not readily available for cellular metabolism
35
BM macrophages contain hemosiderin if
iron stores are normal or high
| stains with prussian blue
36
percent saturation in males & females in transferrin
20-50% males
| 15-50% females
37
total serum iron test
forces transferrin to let go of the iron
38
how many ferric irons can transferrin hold
2
39
total binding capacity
indirecty measures how much transferrin you have
40
transferrin is measured functionally as
TIBC - maximum amount of Fe able to be bound in serum
41
what is transferrin percent saturation
amount of transferrin complexed with iron - usually about 30%
42
the quality of storage iron accompanied by changes in serum iron & TIBC
when storage iron increases, serum iron increases, & TIBC decreases
when storage iron decreases or is absent, serum iron decreases, TIBC increases
43
transferrin saturation in IDA
<16%
44
transferrin saturation in iron overload or hemochromatosis
>55%
45
unsaturated binding capacity test
approximates how many transferrin molecules are present by finding out how much iron can be bound
46
when leftover iron reacts with reagent to make a color, what is the relationship
darker the color, more was available
| the less empty the slots were
47
total iron capacity
sum of the:
total serum + unsaturated iron binding capacity
approximates the amount of transferrin
48
transferrin saturation
~1/3 (33%) of transferrin is saturated with iron
| indicator of amount of iron available for erythropoiesis
49
% transferrin saturation
serum iron / TIBC x 100
50
serum iron normal range
50 - 160 ug/dL
51
TIBC normal range
250 - 400 ug/dL
52
% saturation of transferrin
20 - 55%
53
in an iron deficient patient is there more or less transferrrin
more
54
total iron binding capacity increases in what type of patient
iron deficient patient
55
ferritin
much better measurement than serum iron & TIBC for assessment of iron stores
directly proportional to the amount of storage iron
acute phase reactant
56
what is the amount of serum ferritin in depletion of iron stores
<12 mcg/L
57
what is the amount of serum ferritin in iron overload
>1000 mcg/L
58
low ferritin can be the first indicator of what
iron deficiency anemia
59
transferrin receptor - sTfR
inversely proportional to the amount of body iron
TfR synthesis increases in iron deficiency - only after iron stores are depleted
not affected by inflammation/infection
60
zinc protoporphyrin - ZPP
when iron not available for incorporation into the protoporphyrin ring to form Fe, zinc is incorporated forming ZPP
reflects iron supply over preceding weeks
61
CBC in IDA
normocytic-normochromic cells are replaced by microcytic-hypochromic cells
RDW increased
62
what biochemical transports ferric in the blood stream
transferrin
63
what biochemical has ferrous iron and binds oxygen & CO2
hemoglobin
64
what biochemical is the best indicator of iron stores
ferritin
65
what biochemical is used for deposits of iron in tissues & cells
hemosiderin
66
prussian blue stains
iron
67
erythroblastic island
erythroid progenitors clustering around a central macrophage
68
iron can only enter cells that have a
transferrin receptor
69
free erythricyte protoporphyrin
a heme precursor
70
without iron, porphyrins will
build up "FEP" & complex with zinc to make ZPP
71
serum iron/TIBC x 100% =
transferrin saturation
72
the amount of transferrin can be estimated by the
total iron binding capacity
73
increased ZPP indicates that
the patient is deficient in iron, so zinc takes its place
74
most common anemia
iron deficiency aneia
75
etiology of IDA
diet & increased need
blood loss - GI bleeds & menstruation
malabsorption - celiac disease, gastric bypass, etc
76
stage 1 iron depletion
ferritin decreased
transferrin increased
total iron binding capacity increased
77
stage 2 iron deficient erythropoiesis
FEP & ZPP increased
H&H decreased with microcytes
TfRs increased
78
stage 3 iron deficient anemia
H&H mycrocytic hypochromic very low
79
clinical features of IDA
glossitis
koilonychias
chellitis
blue sclera
80
treatment for IDA
correction of primary disease
oral supplements
transfusion
81
the most common cause of hypochromic anemia is
iron deficiency anemia
82
anemia of chronic disease
common complication in inflammation/infection
| principal pathogenesis is related to hepcidin
83
hepicidin
peptide hormone that is involved in iron absorption & recycling
block release of iron from cells
84
hepicidin's expression is dependent upon
iron availability
| IL-6 mediated inflammatory signaling
85
hepicidin is released by
the liver
86
hepicidin induces
iron sequestration & hypoferremia
87
hepicidin prevents
iron availability for RBC production
88
1-3 months after anemia of chronic disease hypothesis
activated immune system produces cytokines that reduce iron in the circulation
89
1-3 months after anemia of chronic disease characteristics
low serum iron, TIBC decreased, transferrin saturation decreased, ferritin is normal or increased (it's an acute phase protein)
lower EPO; response to EPO is blunted
90
ACD blood smear characteristics
60-70% are normocytic, normochromic & rest are microcytic
retic count not appropriate for degree of anemia
bone marrow has increased stainable iron
FEW & ZPPincrease
91
differential diagnosis of IDA vs ACD is
measurement of plasma transferrin receptors
92
tratement of ACD
treat the disease
| transfuse if needed
93
```
IDA characteristics
hgb
mcv
iron
TIBC
ferrin
rbc
rdw
sTfR
```
```
hgb - low
mcv - low, <80
iron - low
TIBC - high
ferrin - low
rbc - low
rdw - high
sTfR - high
```
94
```
ACD characteristics
hgb
mcv
iron
TIBC
ferrin
rbc
rdw
sTfR
```
```
hgb - low
mcv - normal or <80
iron - low
TIBC - low
ferrin - normal or increased
rbc - low
rdw - normal to slight increase
sTfR - normal
```
95
TfR is elevated in ___ but not in ___
IDA not in ACD
96
types of sideroblastic anemia
inherited
| acquired
97
sideroblastic anemia
iron is incorporated into heme through a series of enzymatic steps
iron is abundant, but heme synthesis is poor
98
inherited sideroblastic anemia
iron incorporated into heme has a defect in one or more of the enzymes
99
inherited sideroblastic anemia is caused by
sex linked form
| autosomal recessive form
100
acquired sideroblastic anemia
iron incorporated into heme blocks one or more of the steps
101
acquired sideroblastic anemia is caused by
drugs, chloraphenicol
| lead poisoning
102
in sideroblastic anemia, prussian blue stain of marrow shows
ringed sideroblasts
103
ringed sideroblasts
normoblasts with iron deposits surrounding the nucleus, awaiting incorporation into heme
104
siderobastic anemia may be improved with
pyridoxing to stimulate heme synthesis
105
```
sideroblastic anemia characteristics
hgb
mcv
iron
TIBC
ferrin
rbc
rdw
sTfR
```
```
hgb - low
mcv - normal
iron - increased
TIBC - decreased
ferrin - increased
rbc - decreased
rdw - increased
sTfR - normal or low
```
106
lead poisoning is what type of anemia
acquired sideroblastic anemia
107
lead poisoning
lead interferes with conversion of ALA to porphobilinogen & incorporation of iron into protoporphyrin IX
108
lead poisoning anemia may be
normochromic/normocytic or microcytic hypochromic
109
lead poisoning characteristics
retic count is high
| basophilic stippling
110
ringed sideroblasts have iron deposits in the
mitochondria
111
defect in the conversion of d-ALA to porphobilinogen can lead to
sideroblastic anemia
112
basophilic stippling
representation of precipitation of rRNA
113
porphyria
enzyme block in porphyrin production
porphyrin precursors build up in tissue
excreted in urine & feces
114
porphyria causes
photosensitivity, motor dysfunction, mental disturbances
115
hemochromatosis
excess iron builds up in tissues
116
types of hemochromatosis
primary
| secondary
117
primary hemochromatosis
hereditary hemochromatosis HFE mutation
118
secondary hemochromatosis
to RBC destruction & transfusion
119
hereditary hemochromatosis
caucasian genetics
| HFE glycoprotein binds transferrin receptors to regulate their affinity for transferrin
120
common mutations in hereditary hemochromatosis
C282Y & H63D
121
hemochromatosis symptoms
joint pain
fatigue
iron ferritin, & transferrin are increased
122
hallmark of hemochromatosis
transferrin saturation
>50% = females
>60% = males
then HFE analysis
123
what is the most common mutation causing hereditary hemochromatosis
C282Y HFE
124
therapy for primary iron overload
therapeutic phlebotomy
125
therapy for secondary overload
therapeutic phlebotomy
| desferrioxamine iron chelation therapy
