Red Blood Cell Disorders-Usera Flashcards
(107 cards)
1
Q
What is erythropoiesis?
A
production of RBCs in bone marrow
2
Q
What specifically stimulates EPO release?
A
interstitial cells in peritubular capillaries of the renal cortex
3
Q
What is the stimuli for EPO release?
A
hypoxemia
anemia
left shift of oxygen binding curve
4
Q
Which factors cause a left shift of the oxygen binding curve, that could stimulate EPO release?
A
higher pH
low DPG
lower temp
5
Q
Which factors cause a right shift of the oxygen binding curve, that could stimulate EPO release?
A
lower pH
high DPG
higher temp
6
Q
What does it mean when you have reticulocytes in the peripheral blood?
A
sign of active erythropoiesis
will see RNA fragments in there
7
Q
What happens to the reticulocyte when you are anemic?
A
it is falsely increased
need to correct for that
Corrected Count=(Actual HCT/45) X Retic Count
8
Q
If your HCT was 20% & your reticulocyte count was 15%…what would your true reticulocyte count be?
A
True Retic=(20/45) X 15%=6.6%
9
Q
What is a normal HCT level?
A
45
10
Q
If the true reticulocyte count is less than the measured reticulocyte count…what does that mean?
A
the bone marrow is working appropriately
11
Q
What does it mean if the true reticulocyte count is less than 3?
A
the anemia is centered in the bone marrow
12
Q
What is extra medullary hematopoiesis?
A
seen in children naturally in the liver & spleen
seen in patients with anemia…sometimes see hepatosplenomegaly & bone marrow expansion, like in the skull
13
Q
Which values are measured on a CBC?
A
hemoglobin
HCT
RBC count
14
Q
Which values are calculated on a CBC?
A
RBC indices
WBC count with diff
platelet count
morphology (observed–if normal, no need for a peripheral smear)
15
Q
How do the hemoglobin ranges for infants compare to adults?
A
they are naturally higher
16
Q
Which type of hemoglobin predominates in the fetus? What does this do to the oxygen binding curve?
A
HbF (2alpha2gamma)
shifts the OBC left
17
Q
Over 6-9 mo, what happens to the HbF cells? What are they replaced by?
A
HbF cells are destroyed by splenic macrophages–>elevated unconjugated bilirubin–physiological jaundice
replaced by HbA (97%), HbA2 (2.5%) & HbF (1%)
18
Q
How does the hemoglobin of children compare to adults? Why is this?
A
it is lower than in adults
b/c higher phosphorus levels increase synthesis of 2,3DPG
get right shifted oxygen binding curve (more efficient oxygen delivery-don’t need as much hemoglobin)
19
Q
How does the hemoglobin level of a female compare to a male?
A
females have lower levels
higher Hb in male b/c of testosterone & don’t have cyclic bleeding
20
Q
What is considered anemia in an adult male?
A
Hb<13.5 g/dL
21
Q
What is considered anemia in an adults non pregnant female?
A
Hb<12.5 g/dL
22
Q
What happens to women’s hemoglobin levels during pregnancy?
A
lower normal ranges during pregnancy due to increased plasma volume
dilutional effect
23
Q
What is considered anemia during pregnancy?
A
Hb<11 g/dL
24
Q
Hemoglobin electrophoresis can be used to detect what?
A
hemoglobinopathies
25
What are normal hemoglobin types & levels for an adult?
HbA 2α2ß (97% in adults)
HbA2 2α2δ (2.5% in adults)
HbF 2α2γ (1% in adults)
26
If you detect abnormal structure on hemoglobin electrophoresis...what does that tip you off towards?
sickle cell anemia
27
If you detect abnormal synthesis on hemoglobin electrophoresis...what does that tip you off towards?
thalassemias
28
What types of clinical findings are consistent with anemia?
```
Fatigue
Dyspnea
Concentration difficulties
Dizziness
Pallor
Pulmonary flow murmur-if the viscosity of the blood is changed enough.
```
29
WHat is MCV? Its equation? Its usefulness?
MCV – mean corpuscular volume (Hct x 1000/RBC)
Useful for classifying anemias
Microcytic = 100 um3
30
What is MCHC?
MCHC – Mean corpuscular Hemoglobin content-w/I the RBC—what is the conc’n of the hemoglobin
average Hb concentration (Hb/Hct)
31
What is RDW?
red cell distribution width
| **shows if the cells have different populations of sizes
32
WHich MCV qualifies you for microcytic anemia? What is your differential dx at this point?
```
MCV<80
iron deficiency
anemia of chronic disease
thalassemia (alpha or beta)
sideroblastic anemia
```
33
Which MCV qualifies you for macrocytic anemia? What is your differential dx at this point?
```
MCV>100
folate deficiency
vitamin B12 (cobalamin) deficiency
```
34
Which MCV means that you are normocytic?
80-100
35
If you have a corrected reticulocyte count of less than 3%...what is your differential dx?
```
blood less of less than 1 week
early stage iron deficiency
early stage anemia chronic disease
aplastic anemia-bone marrow not functioning or present
renal disease
malignancy
```
36
If you have a corrected reticulocyte count of more than 3% & you suspect an intrinsic RBC defect...what is your differential dx?
```
membrane defects:
hereditary spherocytosis
hereditary elliptocytosis
paroxysmal nocturnal hemoglobinuria
Abnormal Hemoglobins:
sickle cell disease
Deficient Enzymes:
G6PD deficiency
pyruvate kinase deficiency
```
37
If you have a corrected reticulocyte count of more than 3% & you suspect an extrinsic RBC defect...what is your differential dx?
```
blood loss of greater than 1 week
immune hemolytic anemia
micro/macroangiopathic
*hemolytic anemia
malaria
```
38
What does a low MCHC imply?
implies defect in Hb synthesis-like a microcytic anemia
39
What does a high MCHC imply?
implies spherocytosis
40
Describe spherocytosis.
you will see no central pallor on RBC
can't see the biconcave shape
sphere is packed with hemoglobin
high MCHC
41
What does an increased RDW indicate?
2 different populations of cells
seen in iron deficiency anemia
anisocytosis--RBCs different sizes
42
T/F Mature RBCs lack mitochondria.
True.
| This means no TCA, beta oxidation or ketone body synthesis.
43
Which biochemical pathways do RBCs participate in?
anaerobic glycolysis--Cori Cycle
| pentose phosphate pathway--make glutathione
44
What is glutathione?
endogenous antioxidant. keeps RBCs alive despite oxidative damage
45
What is ferritin?
soluble iron binding storage protein
46
How can you estimate the levels of ferritin in the bone marrow?
serum levels correlate
47
What synthesizes ferritin in the bone marrow? What stimulates this synthesis?
macrophages synthesize it
| driven by IL-1 & TNF-alpha
48
What is decreased ferritin indicative of?
iron deficiency
49
What is increased ferritin indicative of?
anemia of chronic disease
| iron overload
50
Serum iron represents iron bound to ____.
transferrin
51
Where is iron & transferrin produced?
liver
52
What is the normal iron conc'n?
100 micrograms/dL
53
Decreased iron levels could indicate what?
iron deficiency
| anemia from chronic disease
54
Increased iron levels could indicate what?
iron overload:
transfusion
sideroblastic
hemochromatosis
55
What is TIBC? What is its normal level?
total iron binding capacity
300 micrograms/dL
fraction of iron bound to transferrin
56
What is the equation for iron saturation? What is a normal level? What is its significance?
Iron sat=serum iron/TIBC x 100
**percentage of iron binding sites on transferrin
Normal: 33%
57
What happens to ferritin, transferrin, TIBC etc when you are in iron deficiency?
ferritin is low b/c of the iron deficiency
the liver is told to make more transferrin to compensate
TIBC goes up
58
What happens to ferritin, transferrin, TIBC etc when you are experiencing anemic chronic disease?
IL1 & TNFalpha are released as a result of a chronic disease.
As a result, more ferritin is produced.
Thus, the liver makes less transferrin.
the crazy part is the release of hepcidin from the liver b/c of chronic disease...makes it so that iron can't be transferred from ferritin to transferrin.
hard to get the iron into the peripheral blood
59
What happens to ferritin, transferrin, TIBC etc when you are in iron overload?
you have a ton of iron, so you have a ton of ferritin.
this tells the liver to make much less transferrin.
I think TIBC goes down.
60
Iron deficiency anemia has what kind of MCV? Where is dietary iron resorbed?
Most common anemia!!!
MCV<80
dietary iron resorbed in duodenum
61
Describe the absorption of iron.
happens in the duodenum
oxidizied form (like Fe+3) can't be resorbed in SI
gastric acid helps free elemental iron
vit c redues ferric iron
iron incorporated into hemoglobin
some stored in bone marrow macrophages
can be found in myoglobin or enzyme cofactors
62
Which demographics often exhibit iron deficiency anemia?
toddlers 1-2 years of age
| females 12-49 yo w/ menstrual loss
63
What are 4 broad categories of reasons for iron deficiency anemia?
blood loss
inadequacy
overutilization
destruction
64
What are some causes of blood loss that prompt iron deficiency anemia?
```
GI bleed
peptic ulcer disease
Hookworm infection
NSAIDS/Ulcers
Meckels
Menorrhagia
```
65
What are some causes of inadequacy that prompt iron deficiency anemia?
Prematurity
Restricted diets-vegan
Malabsorption
(e.g. celiac--but no UC etc)
66
What is a cause of over utilization that can prompt iron deficiency anemia?
pregnancy--lactation
67
what are some causes of destruction that can prompt iron deficiency anemia?
hemolytic anemias
| pnh
68
What is plummer vinson syndrome? How does it relate to iron deficiency anemia?
```
several of the following symptoms
esophageal web
achlorohydria
glossitis
koilonychia
```
69
What is esophageal web?
fibrous band that grows & constricts the esophagus
| causes dysphagia issues for solids, not liquids
70
What is glossitis & angular stomatitis?
super red inflamed tongue
| red lines going out from the corners of the mouth
71
What is koilonychia?
spoon nailing...see the nail tilt up.
72
What is achlorhydria?
production of gastric acid in stomach is low
| get bacterial overgrowth in the intestines
73
What are the lab findings for iron deficiency anemia?
```
Decreased MCV
Decreased serum iron, iron sat
Decreased serum ferritin
Increased TIBC, RDW, higher transferrin
Thrombocytosis – reactive
WBCs could be elevated or lowered
```
74
Where is anemia of chronic disease commonly seen? What is it?
commonly seen in the hospital setting
decreased synthesis of heme
inadequate renal secretion of EPO
hepicidin released by liver as a part of inflammation (can't release iron to transferrin)
75
What are the lab findings for anemia of chronic disease?
Decreased MCV
Decreased serum iron, TIBC, and iron sat
Increased serum ferritin
decreased transferrin
76
What are the thalassemias?
aut recessive
quantitative issue-nothing wrong with your hemoglobin, just not making enough
don't get enough normal globin chains
protective against malaria!
77
Where are the thalassemias most prevalent?
mediterranean
africa
southeast Asia
78
Where do you find the genes for beta chain?
one copy of bet agent on each chromosome 11 (2 copies total)
79
Where do you find the genes for the alpha chain?
2 copies of this gene found on each chromosome 16 (4 copies total)
80
What's the deal with beta thalassemia?
problem with upstream promoter region of beta globin gene
gives mild microcytic anemia
too few beta chains--compensate with HbA2 & HbF (detected by electrophoresis)
81
What are the lab values for beta thalassemia?
```
Decreased MCV, Hemoglobin and hct
Increased RBC count-b/c of increased plasma volume
Normal RDW and ferritin
Decreased HbA 2α2ß
Increased HbA2 2α2δ and HbF 2α2γ
```
82
How should you usu treat beta thalassemias?
usu you shouldn't treat!!
don't want to transfuse b/c you could get iron overload
also new blood antigens could cause hemolytic anemias
83
What is beta thalassemia major? What is another name for it?
Aka cooley’s anemia ß0ß0
Severe hemolytic anemia
Rbc’s accumulate α chain inclusion, and are removed by splenic macrophages
84
What types of labs do you see with beta thal major?
Increased RDW and reticulocytes
ZERO HbA 2α2ß
Increased HbA2 2α2δ and HbF 2α2γ
85
What treatment is required for beta thal major?
REQUIRES LONG TERM TRANSFUSION
86
What's the deal with alpha thal?
gene deletion problem, not a problem with the promoter
2 gene deletions=alpha thal trait
can see splenomegaly
87
African Americans have what type of alpha thal usu?
(a/- a/-)
| experience mild anemia
88
Asians have what type of alpha thal trait? WHat type are they at risk for?
(-/- a/a)
increased risk for severe form:
(-/- -/-) incompatible with life
89
What are the lab values for alpha thal?
Decreased MCV, Hb, Hct
Increased RBC count
Normal RDW, ferritin
90
What would be the genotype of a pt who was an alpha thal carrier but not symptomatic?
a/- a/a
| no abnormalities
91
What would be the genotype of a patient with alpha thal minor...who had only mild microcytic anemia?
African Americans:
a/- a/-
Asians:
-/- a/a
92
What would be the genotype for a pt with Hb H Disease? What would be their symptoms?
-/- a/-
hemolytic & microcytic anemia
splenomegaly
could die from renal failure if you have had a splenectomy
93
-/- -/- causes what?
fatality
| hydrops fatalist
94
What can cause sideroblastic anemia?
```
chronic alcoholism --affects mitochondria!
pyridoxine deficiency (vit B6)
lead poisoning
iron overload
hereditary--x linked recessive
```
95
Coincidentally...many chronic alcoholics also have what? Making sideroblastic anemia that much more likely...
pyridoxine deficiency (vit B6)
96
WHat is sideroblastic anemia?
defect in heme synthesis within the mitochondria
| iron can't be incorporated into heme
97
What is the rate limiting step in heme formation?
delta ALA conversion into porphobilinogen
98
Which heme synthesis steps does chronic alcoholism affect?
pretty much all of them
| have general effect on mitochondria b/c EtOH is a mitochondrial toxin
99
Why does pyridoxine deficiency (vit B6) cause sideroblastic anemia?
b/c it is a cofactor for delta ALA synthase
rate limiting step in heme synthesis!!
alcohols have this deficiency
also people who have undergone isoniazid (INH) therapy often have this deficiency
100
What is isoniazid therapy used to treat? Why could this cause pyridoxine deficiency & sideroblastic anemia?
used to treat TB
complexes with Vit B6 (pyridoxine)
get a deficiency & then can't execute the rate limiting step for heme synthesis
sideroblastic anemia!!
101
Lead poisoning is the most common cause of sideroblastic anemia in which age group?
little dudes 1-5 yo
eating lead-based pain
being in batter & ammunition factories
102
Lead denatures which 3 critical enzymes?
ferrochelatase
ala dehydrase
ribonuclease
103
What happens after ferrochelatase is denatured by lead?
iron can't bind with protoporphyrin
104
What happens after ALA dehdyrase is denatured by lead?
causes increase in delta ALA
105
What happens after ribonuclease is denatured by lead?
prevents the breakdown of ribosomes
| causes basophilic stippling
106
What are the clinical findings for sideroblastic anemia?
things caused by delta ALA accumulation!
Abdominal colic (iron incorporated into GI)
Encephalopathy (due to increased δ–ALA)
growth retardation (delta ALA deposits around growth plates)
Peripheral neuropathy--dALA is toxic to neurons...increases vascualr permeability & edema & demyelination
Nephrotoxicity
Burton’s linE-blue line at gum line
107
What are the lab findings for sideroblastic anemia?
Elevated lead levels (urine is the best test)
Increased iron, iron sat, and ferritin
Decreased MCV and TIBC
Ringed-sideroblasts in marrow
