Anemia Flashcards
(213 cards)
1
Q
Anemia
A
insufficient red cell mass to adequately deliver oxygen to peripheral tissues
2
Q
measurements to define anemia (8)
A
hemoglobin concentration hematocrit red blood cell count MCV MCHC RDW WBC count and differential platelet count
3
Q
percent volume of red cells in blood
A
hematocrit
4
Q
variation in Hgb and Hct based on gender
A
higher than ever at birth
decrease to lower than adults in childhood
puberty go back to adult levels
menstruating women have lower values
5
Q
How can we ID retics?
A
presence of mRNA
6
Q
How are retics counted?
A
—as the percent of 1000 red cells counted (normal 0.4-1.7)
7
Q
absolute retic count?
A
%retics x RBC count
8
Q
reticulocyte index
A
ratio of how many fold beyond baseline the production of red cells is:
RI = Retic Count x (PatientHgb /Normal Hgb) x 1/stress factor
where 1.5 = mild
2 = moderate
2.5 = severe anemia
9
Q
What should the RI be for a health individual?
A
1-2
10
Q
2,3-DPG and anemia?
A
If develops over weeks, 2-3DPG compensatory mechanism will help O2 dissociate in tissue
If develops acutely, 2-3DPG does not have enough time to esatblish compensatory mechanism
11
Q
Symptoms of anemia
A
shortness of breath fatigue rapid heart rate dizzy pain with exercise pallor
12
Q
signs of anemia
A
tachycardia
tachpnea
dyspnea
pallor
13
Q
Question one in the classification of anemias
A
Are there any additional hematologic abnormalities
14
Q
If anemia is associated with additional hemotologic abnormalities (e.g., thrombocytopenia, leukopenia, neutropenia) what should you consider?
A
look for infiltrative and proliferative processes (e.g., leukemia, lymphoma, aplastic anemia)
15
Q
If the only manifestation is anemia, what should be your next question?
A
Is there an appropriate reticulocyte response to anemia?
16
Q
If the only manifestation is anemia and there is an increase in reticulocytes, what should you consider?
A
increased red cell destruction (hemolysis) or hemorrhage
17
Q
If the only manifestation is anemia and the retic count is not increased and there is no other evidence for hemolysis, what should you consider?
A
the type of anemia based on the MCV and size…i.e., normocytic, macrocytic, or microcytic
18
Q
in what form does iron exist?
A
Iron exists in two valence states, ferric and ferrous - activity may depend on specific state
19
Q
iron in aqueous solution
A
in aqueous solutions, iron forms insoluble hydroxides unless bound to a specific protein or other compound
20
Q
at what pH is iron more soluble?
A
low
21
Q
how does the body control iron balance?
A
controlled by absorption
there is no active excretion mechanism
22
Q
iron losses?
A
losses each day are small
- exfoliation of skin and mucosal surfaces (GI/skin)
- in urine or with menstruation
23
Q
is iron ever free in the body?
A
no
24
Q
majority of iron is contained?
A
hemoglobin (65%)
25
primary storage form of iron?
ferritin and hemosiderin are the primary storage forms of iron (25% of the total body iron, mostly intracellular)
26
in addition to hemoglobin, what other oxygen binding protein binds iron and how much?
myoglobin (6%)
27
In addition to ferritin and hemosiderin, plus the oxygen binding proteins, what transport protein binds iron?
transferrin
a very small amount of iron is bound to transferrin, the transport protein which moves the iron to the tissues requiring iron - particularly the developing erythroid precursors.
28
Aside from the major iron binding proteins, what is the remaining
a whole variety of enzymes, including catalases, peroxidases, cytochromes, and other proteins which a critical to basic metabolic processes of the cell
29
Where does the absorption of iron take place?
mucosal surface of the duodenum
30
Hemoglobin iron form
Fe2+ (ferrous)
31
myoglobin iron form
Fe2+ (ferrous)
32
transferrin iron form
Fe3+ (ferric)
33
transferrin iron form
Fe3+ (ferric)
34
Plasma Fe transporter?
transferrin
35
Intracellular Iron sotarage?
Ferritin and hemosiderin
36
How do we get iron into mucosal cell?
DCYTB converts Fe3+ to Fe2+ then comes into cell through DMT1
37
Once iron is inside mucosal cell what happens?
Can be stored as ferritin
Or
Can cross basolateral membrane through ferroportin (Haphaestin coverts back to Fe3+)
38
what compound forms pore in basolateral membrane of mucous cell to allow mobilization of iron from cells into blood stream?
ferroportin
39
What compound produced by the liver decreases ferroportin?
hepcidin
40
types of iron absorbed?
elemental adn heme bound
41
Intraluminal factors influencing iron absorption (5)
```
gastric (low pH / gastroferrin)
presence of proteins / amino acids (more)
vitamin c (more)
phytates / oxalates (less)
amount of iron ingested
```
42
Hephaestin
oxidizes Fe2+ to Fe3+ as it moves out of basolateral ferroportin to bind plasma transferrin
43
Extraluminal factors influencing iron absorption?
Erythropoietic activity (up)
44
Transferrin
main transport protein for iron (Fe3+)
| binds 2 moles / mole
45
Where does transferrin go?
finds its way to the bone marrow and the maturing normoblasts where it binds transferrin receptors on the surface of cells where it is directed into cell and incorporated into hemoglobin
46
Who turns over erythrocytes?
macrophages in the spleen
47
what do macrophages do with the iron?
macrophages sequester iron in ferritin stores
48
is there extracellular ferritin?
only small amount
49
what happens to the ferritin bound iron in macrophages
evenutally iron from the storage pool may be released from teh cell and bound by transferrin again
50
what is the difference between ferritin and hemosiderin
in hemosiderin the iron is not completely soluble and bioavailble
51
what is hepcidin
25 aa antibacterial peptide produced by hepatocyte
negative regulator of iron absorption / transport / release
52
When do we make hepcidin
inflammation / infection / iron overload
53
hepcidin implication for hemochromatosis
deficiency of hepcidin
54
how does hepcidin increase iron retention in macrophage?
inhibits ferroportin - causes increase in macrophage retention - contributing to anemia
55
how does hepcidin influence iron resistant iron deficiency anemia?
implicated because iron won't help if iron won't be released
56
what is a negative regulator of iron absorption / transport / and release
hepcidin
57
Hepcidin release from hepatic cells during infection/inflammation -->
increased accumulation in macrophagic ferritin
58
splenic macrophage and iron?
stores Fe3+ in ferritin
59
Development of iron deficiency... first thing we see?
depletion of iron stores --> increase in iron absorption
60
Initial stage of iron deficiency, what is going on with transferrin?
should be the same saturation initially because we have only depleted stores - we are still going to be able to make normal amount of hemoglobin
61
Moderate stage of iron deficiency
We start to see a decrease in the serum as well as stores - then we see increase in iron binding capacity of transferrin and an incrase in iron absorption - start to see porphyrin rings that don't have any iron in them (Protoporphyrin)
62
State of things when anemia sets in
```
our iron binding capacity will be elevated
our ferritin will be low saturation
we will have increased absorption
decreased serum iron
increased protoporphyrin
micro/hypo erythrocytes
```
63
Hepcidin and ferroportin?
Hepcidin causes inhibtioion of ferroportin - leading to increased retention in macrophages contributing to anemia
64
Hepcidin is associated with which biological process?
inflammation/infeciton or iron overload
65
iron deficiency anemia is which kind?
micro/hypo
66
In addition to hematopoietic anemia, which other systems are affected?
```
neuromuscular
epithelial
upper GI
Lower GI
Immune
```
67
IMicrocytic Iron deficiency anemia is most commonly seeni in?
Infants / Teen grils
68
Etiology of iron deficiency anemia (microcytic?)
decreased intake
increased loss
increased need
69
Iron deficiency anemia
| Oxygen carrying capacity?
Hemoglobin and Hematocrit are down
70
Iron deficiency anemia
| reticulocytes?
Decreased production :(
71
Iron deficiency anemia
| MCV?
Microcytosis
| Decrased MCV
72
Iron deficiency anemia
| MCHC
Decrased
73
Iron Defieicney anemia
| RDW
Increased
74
Iron deficiency anemia
| Serum Fe?
Down
75
Iron deficiency anemia
| TIBC
Increased
76
Iron deficiency anemia
| ferritin level?
decreased
77
iron deficiency anemia
| free erythrocyte proprophyrin (FEP)
Increased
78
Treatment of iron deficiency anemia
Oral iron
79
Normalization cascade iron deficiency anemia?
Serum iron --> Hbg/rectic --> ferritin --> MCV/FEP/RDW
80
Too much iron =
hemachromatosis
81
Etiology of hemachromatosis
too much in diet
too much absorption (HLA-H)
Repeat transfusions
82
Dangers of hemachromatosis
cardiac
liver
pancreas
83
serum iron
ferritin
liver iron
in hemachromatosis
all will be increased
84
treatment
| hemochromatosis
therapeutic phleb
85
treatment
| hemosiderosis
iron chelators
86
anemia of chronic disease (6) associated conditions
```
chronic infection
chronic inflammation
malignant disease
lead intoxication
renal insufficiency
endocrine issues
```
87
pathophysiology of anemia in neoplasms and sepsis
increased TNF leads to decreased iron and EPO
increased INF-B
both lead to inhibition of erythroid proliferation and decreased RBC production
88
pathophysiology of anemia in chronic infeciton and inflammation
increased IL1 release leads to decrease iron and decrease EPO
Increased INF-gamma
both lead to inhibition of erythroid proliferation and decreased RBC production
89
pathophysiology of lead intoxication anemia
lead inhibits enzyme that puts iron on prophyrin ring and inhibits protoporphyrin synthesis
this lead to decreased heme + globin
90
pathophysiology of renal insufficiency anemai
decreased EPO --> decreased erythroid proliferation
91
We have a patient who comes in with fever, arthalgias, and fatigue...
Mild to moderate anemia (Hgb 8/12)
Normochromic, normocytic or microcytic with some hypochromia
```
They have decreased serum Fe
Decreased TIBC
normal to increased ferritin
decreased EPO for Hct
Decreased Rectic
```
What do you think they have?
Anemia due to chronic inflammation or infeciton
92
What are distinguishing features of chronic inflammaiton or infeciton anemia?
Unlike iron deficiency, they will have decreased TIBC and normal to increased ferritin
93
Chronic inflammation usually which type?
Normocytic or microcytic
94
Chronic inflammation serum Fe?
down
95
Chronic inflammation TIBC?
down
96
Chronic inflammation ferritin
normal to increased
97
chonic inflammation EPO?
down for Hct
98
chronic inflammation retic count?
down
99
Personality changes / irritaiblity / weight loss/ nausea etc are clinical features of which anemia?
lead toxicity
100
lead toxicity anemia usually which type?
microcytosis and hypochromia
101
what distinguishing features might we see with lead intoxciation anemia
increased zinc protoporphyrin
| basophilic stippling
102
what distinguishing features will we see in renal insufficiency anemia?
what type?
EPO deficiency
| Normocytic
103
Hypothyroidism, type?
most normochromic and normocytic, may be micro or macro
104
Hyperthryoidism, type?
normo, may be micro
105
When should we transfuse?
only transfuse red cells when the severity of anemia has potenital for cardiovascula decompensation
106
when should we use EPO? (2)
an absolute deficiency
or
a decrease our of proportion to Hct, for which a response has been documented
107
Sideroblastic anemia
underproduction
| impaired protoporphyrin production or incorporation of iron
108
accumulation of iron in mitochondria characteristic of
sideroblastic
109
Folic acid and B12 are critical for synthesis of
```
methionine from homocystiene
which is needed for
purine and pyrimidine biosynthesis
which are needed for
thymodylate for DNA synthesis
```
110
what happens with Folate and B12 deficiencies (to cells)
Fucks with maturation
| Cells increase in size and arrest in S phase --> destroyed --> ineffective erythropoiesis
111
in addition to anemia, what else might we see with folate / B12 deficiency?
neutropenia
| thrombocytopenia
112
where is B12 absorbed?
terminal ileum
113
what does B12 absorption require?
IF from gut
114
What is the carrier of B12?
TC-II
115
Where is folic acid absorbed?
jejunum
116
What happens once folic acid is absorbed?
reduced/methylated
117
Do B12 of folic acid stores last longer?
B12
118
Causes of B12 deficiency? (5)
```
Autoimmune
IF deficiency
Malabsorption
Defective transport / Storage
Metabolic defect
```
119
Causes of folate deficiency? (6)
```
dietary insufficiency
malabsorption
drugs and toxins
inborn error of metabolism
increased demand (hemolysis/pregnancy/psoriasis)
increased loss or metabolism
```
120
what type of anemia results from folate and vitamin b12 deficiencies
megaloblastic
121
does folate or b12 deficiency develop more rapidly
folate
122
is folate or b12 more likely to be associated with alcohol abuse / poor nutrition
folate
123
is folate or b12 more likely to be associated with malabsorption
B12
124
In folate and b12 deficiency what happens in bone marrow?
megaloblastic changes seen in both red cell and white cell precursors - at any stage, large, more immature nuclei
125
In folate and b12 deficiency what happens with erythrocytes in bone marrow?
erythroid hyperplasia
126
What happens with cytoplasmic maturation in folate and b12 deficiency?
normal
127
in folate and b12 deficiency whats up with the peripheral blood?
MCV>97 - macrocytosis
ovalocytes
hypersegmented nuclei of neutrophils
128
As anemia progresses in severity in folate and b12 deficient anemia what happens in peripheral blood?
```
nuetropenia
thrombocytopenia
increased bilirubin
LDH
RI
```
129
Which anemia manifests neurologically
B12
130
Good way to distinguish Folate vs B12?
A reaction involving vitamin
B12 but not folate is the synthesis of succinyl CoA from methylmalonyl CoA. Thus, in B12 but
not folate deficiency, methylmalonic acid levels are increased, making measurement of
methylmalonic acid a good way to distinguish the two.
131
What fraction of B12 deficiency arise from GI?
95%
132
Management of B12 deficiency?
1 mg injections weekly for first few weeks...then monthly
133
How do we manage B12 if absorption not issue?
orally 2x/day
134
How do we manage folate?
orally
135
Folate / B12 anemia response to treatment?
reverses quickly
| nuerological slower
136
what is hemolysis?
decrease in red cell survival or increase in turnover beyond normal range
137
how long do RBC take to develop in BM
10-14
138
How long are reticulocytes in marrow?
3
139
How long are retic in peripheral blood
1
140
How long do RBC survive
120 +/- 20
141
During stress what may happen to the time frame of reticulocyte release?
decrease BM maturation time to
| 5-7 days rather than 10-14
142
Normal production of RBC (% red cell mass / day)
1
143
How much may RBC production increase?
6-8 fold
144
where does most RBC turnover take place?
spleen (extravascular 90%)
145
where does minor RBC turnover take place?
intravascular 10%
146
do we see changes in RBC enzyme activity with age?
yes this is normal
147
do we see oxidative injury with RBC over time?
yes normal
148
do we see changes in calcium balance?
yes normal
149
do we see changes in carbohydrates and surface constituents?
yes, normal
150
do we see antibodies to RBC surface constituents
apparently, but that's weird
151
extravascular RBC destruction is mediated by?
macrophages of the reticuloendothelial system
152
in which type of hemolysis do red cells release hemoglobin into the circulation
intravascular
153
what happens when hemoglobin is released into the circulation in intravascular hemolysis?
dissociates into dimer which may immediately bind to haptoglobin
haptoglobin is removed from circulation by liver
iron can be oxidized to form methemoglobin...dissociation of globin releases metheme which may bind to albumin or hemopexin - these can be taken up by parenchymal cells and converted to bilirubin
154
if not dissociated to yield bilirubin, what alternative pathway may dimeric forms of methemoglobin / hemoglobin take in intravascular hemolysis?
filtered and not reabsorbed by kidney and appear in urine
155
in which process are red cells ingestested by macrophages of the RE system
extravascular hemolysis
156
what happens when RBC is ingested by macrophages in EVH?
the heme is separated from the globin, iron removed and stored in ferritin, and the porphyrin ring converted to bilirubin and released from the cell
157
what happens to bilirubin that is released by macrophages?
taken up by transport system in the liver and converted to water soluble compound via conjugation of glucouronic acid
158
what happens once glucouronic acid is conjugated to bilirubin in liver parenchymal cells?
secreted into the biliary tract and small bowel - the glucouronic acid is removed and bilirubin converted to urobilinogen and other water soluble pigments
159
what happen with urobilinogen?
may cycle between teh gut and liver (entero-hepatic circulation) or excreted by the kidney into the urine...
160
decrease in serum haptoglobin
hemoglobin in urin or plasma
increase in metheme / methemalubin
suugests?
intravascular hemolysis
161
spectrin deficiency is most common abnormality seen in
hereditary spherocytosis
162
hallmark of hereditary spherocytosis
loss of plasma membrane and formation of microspherocyte
163
basic pathophysiology of hereditary spherocytosis
spectrin, ankyrin, or band 3 defects weaken the cytoskeleton and destabilize the lipid bilayer
164
consequence of spherocyte formation?
decreased RBC deformability and entrapment in the spleen
165
ultimate fate of RBC in hereditary spherocytosis
removal by macrophage
166
clinical presentation of hereditary spherocytosis
variable degree of anemia as well as jaundice and splenomegaly -
1/3 has hyperbilirubinemia as neonates
167
hereditary spherocytosis genetics
25% autosomal recessive
| 75% autosomal dominant
168
splenectomy usually resolves clinical manifestations of which condition?
hereditary spherocytosis
169
hereditary spherocytosis lab features
```
variable Hct and Hgb
increased retic
decreased MCV
spherocytes on smear
unconjugated hyperhiliruinemia
```
170
clinical complications of herediatry spherocytosis
aplastic crisis
| bilirubin stones
171
enzyme disorder anemias
G6PD
| PK
172
G6PD deficiency presents with
presents with hemolytic anemia
173
G6PD genetics
X linked recessive
174
G6PD enzyme
important enzyme in the pathway which provides protection again oxidant stress - loss of the enzyme actitvity in the red cells results in inability to restore reduced glutathione - with oxidant stress
175
G6PD and oxidant stress -->
denatured hemoglobin attaches to the membrane and spectrin may be damaged - decreased deformability
176
G6PD clinical presentation
intermittent episodes of acute hemolytic anemia and hyperbilirubinemia associated wtih oxidant stress
177
G6PD characteristic cells
blister bite
178
Pyruvate Kinase deficiency
decrease in converting phosphoenolpyruvate to pyruvate results in decreased ATP, increased 2,3-DPG, loss of membrane plasticity and increase in rigidity and destruction in the spleen
179
PK deficiency clinical presentation
variable chronic anemia, hemolysis, increased reticulocytes, and no specific morphology
180
Cold antibodies
activate complement
181
Warm antibodies
incite splenic macrophage to antibody mediated phagocytosis through Fc receptor
182
Warm or cold antibodies act via intravascular hemolysis?
cold
183
warm or cold antibodies act via extravascular hemolysis?
warm
184
direct antiglobulin test
evaluates for presence of IgG c3d or c4d on the surface of the patients red cells by addition of Coombs reagnet which has antibodies for IgG, C3d, and C4d causing agglutination
185
indirect antiglobulin test
detect the ability of patient's serum to bind IgG and or complement to test (normal) red blood cells - by definition, autoimmune hemolytic anemia should have a positive DAT
186
Clinical characteristics of AIHA
```
acute or chronic onset anemia
pallor
jaundice
dark urine
splenomegaly may occur
```
187
retic count in AIHA?
increased
188
bilirubin in AIHA
increased
189
is there hemoglobin in urine in AIHA?
Depends on the extent of intravascular hemolysis
190
Which AIHA will exhibit psotiive DAT (strong IgG with weak complement)
warm
191
which AIHA will exhibit positive DAT (complement only no IgG)
cold
192
spleen is critical for
clearnace of intravascular microbes
193
spleen important in children for development of
humoral response and is the origin of IgM agglutinins
194
most significant complication of splenectomy?
bacterial sepsis associated with S pneumoniae
195
risk of sepsis following splenectomy greatest in who
children under 5
196
increased mortality from sepsis if splenectomy
200x
197
pre-surgical splenectomy protocal
vaccination against
H influenza
S pneumoniae
meningococcus
198
after splenectomy give?
penicllin
199
most RBC turnover is extravascular occuring in the
spleen
200
where does met-heme come from?
during intravascular hemolysis, iron is released from cell - converts to ferric form and yield met-heme which then binds albumin --> methemalbumin which is pulled out by the liver
201
hemolytic anemia
| RBC morphology
spherocytes / fragments
202
hemolytic anemia
| retic
increased
203
bilirubin in hemolytic anemia
up because more Hgb is present to RE system - most unconjugated
204
Hemolytic anemia
| Hbg?
up
205
hemolytic anemia
| haptoglobin
low
206
hemolytic anemia
| methemalubin
up
207
hemolytic anemia
| housekeepign enzymes
up
208
familial hereditary disorder characterized by anemia, intermittent jaundice, splenomegaly, and responsiveness to removal of spleen
herediatry spherocytosis
209
most common molecular abnormality in Hereditary spherocytossi
spectrin
210
we see abnormal response to hypotonic stress (osmotic fragility) in what disorder?
hereditary spherocytosis
211
what is destablized in HS?
Lipid bilayer --> mkcrospherocytosis
212
the loss of membrane surface area and subsequent microspherocytosis in HS leads to what consequence?
decreased RBC deformabiltiy and incrased entrapment in the splenic cords --> macrophage removal
213
```
lab features of HS
Hct?
Hgb?
Retic?
Mchc?
mcv?
```
vatiation in Hct and Hgb
retic up
mchc up
mcv down
also see spherocytes
unconjucated hyperbilirubinemia
increased osmotic fragility
