Exam 1 Flashcards
1
Q
Fetus hematopoietic organs
A
liver & spleen
2
Q
adult hematopoietic organs
A
bone marrow- pelvis, ribs, vertebrae, skull, epiphyses of the femur & humerus
3
Q
Blood cells are produced in the:
A
bone marrow
4
Q
bone marrow contains:
A
stem cells
5
Q
stem cells produce three types of blood cells:
A
WBCs, RBCs, & plts
6
Q
blood islands
A
clusters of stem cells in the human embryo
7
Q
chief site of blood cell formation until shortly before birth
A
liver and spleen
8
Q
_____ of development, hematopoeisis commences in the bone marrow
A
fourth month
9
Q
up until age 18, all of the marrow throughout the skeletonis hematopoietically active. after that:
A
only the vertebrae, ribs, sternum, skull, pelvis & proximal areas of humerus & femur are active
10
Q
in adults, only about ___ of marrow space is active in hematopoiesis
A
half
11
Q
hematon:
A
separate microenvironments of developing progenitor cells. isolated by reticular cells
12
Q
important hematopoietic components that provide growth factors, collagen & cell adhesion proteins
A
endothelial cells, firboblasts, macrophages, & adipocytes
13
Q
pluripotent
A
stem cells- unique potential to ultimately become any of the mature hematopoietic cells
14
Q
stem cells are characterized by:
A
high proliferative capacity
potential to differentiate along all lineage pathways
property of self renewal
15
Q
important property of stem cells
A
property of self renewal- ability to generate additional stem cells through mitosis w/out differentiation
16
Q
hematopoietic cytokines
A
protein molecules actively secreted by cells of bone marrow & influence proliferation & differentiation of stem cells into mature blood cells
17
Q
Platelets & RBCs do not have
A
a nucleus
18
Q
WBCs include:
A
granulocytes (eos, baso, neutro)
monocytes/macrophages
lymphocytes (B&T cells)
19
Q
most common PMN
A
neutrophils
20
Q
neutrophils have
A
multi-lobe nucleus
21
Q
primary neutrophils contain
A
proteins (defensisns), proteolytic enzymes, lysozymes
22
Q
secondary neutrophils contain
A
NADH oxidase components
23
Q
Basophils
A
basic
involved in allergic rxns
Heparin & histamine
24
Q
Eosinophils
A
acid
defense against paracites
high numbers in GIT & lungs
25
Monocytes circulate in the ___ and
| marcophages are found in ____
blood stream; tissues (liver & lymphh nodes)
26
most common type of blood cell
RBCs
27
diameter of a typical RBC
6-8 microns
28
RBCs produce energy via
glycolysis
29
production of RBCs can be stimulate dby
erythropoietin
30
main sites of destruction of RBCs
liver & spleen
31
hemoglobin is eventually excreted as
bilirubin
32
platelets aka
thrombocytes
33
platelets are
fragmented pieces of megakaryocyte cytoplasm released from bone marrow into the blood stream
34
what is required for the differientiation of stem cells into platelets
thrombopoietin
35
CBC contains
RBC & WBC count, Hgb, Hct, RDW, reticulocyte count, platelet count & mean platelet count, MCV< MCH< MCHC
36
Hct
% volume of blood composed of RBCs
| usually 3X Hgb
37
Anemia
reduction in the oxygen carrying capacity of blood
| decrease RBC volume measured by Hct or Hgb
38
anemia classification based on:
appearance (size) of RBCs
degree of Hgb- color
underlying mechanism
39
< folate or B12 causes defective
DNA synthesis and therefor can't make RBCs
40
< iron cause deficient
heme synthesis
41
hemolytic anemia
> RBCs destruction
shortened lifespan of RBCs
accumulation of hgb catabolism products
> erythropoiesis
42
spherocytosis:
abnormal shape, can't fit through vessels
| disorder of RBC membrane cytoskeleton
43
thalassaemia syndromes
deficient globin synthesis
44
sickle cell anemia
structural abnormal globin synthesis
45
extravascular hemolysis
phagocytic destruction of senescent RBCs takes place within the phagocytic cells of the spleen
46
intravascular hemolysis
lyses of RBCs occur within the vascular compartment. occurs when RBCs are damaged by mechanical injury, complement(transfusion), exogenous toxic factors (malaria)
47
characteristics of intravascular hemolysis
hemoglobinemia, hemoglobinuria, jaundice, methemoglobinuria(oxidized Hgb), hemosiderinuria
48
haptoglobin levels go ____ in intravascular anemia
down
49
characteristics of extravascular hemolysis
do NOT have Hgb-emia or Hgb-uria
jaundice
mayhave decreased haptoglobin
may have hypertrophy of mononuclear phagocytes-> splenomegaly
50
hereditary spherocytosis
anemia due to RBC membrane protein disorder
autosomal dominant
RBC are spherical due to deficiency in RBC protein spectrin
can have chronic hemolytic anemia
splenomegaly
jaundice
51
spectrin
major component of RBC cytoskeleton
| along with Band 3, are responsible fore maintenance of normal shape, strength & flexibility
52
G6PDH deficiency
leads to hemolytic anemia due to inability to neutralize oxidative stress
H2O2 accumulates in RBCS
53
how does accumulation of H2O2 cause RBC lysis?
cause oxidation of sulfhydryl groups like globin chains in RBCs-> denaturation of Hgb & formation of Heinz bodies
54
Heinz bodies damage
RBC membrane and cause extravascular hemolysis
55
causes of oxidative stress
Drugs, infections, fava beans
56
Coombs' test
distinguish between anemia caused by immune mediated response & other forms of anemia
Coombs- antihuman antibodies
57
Direct Coomb's test
detect antibodies bound to RBCs
58
Indirect Coombs' test
detects antibodies in the serum
59
3 key defects in erythropoiesis:
1. defective DNA synthesis due to lack of B12 or folate- Macrocytic
2. impaired heme synthesis due to lack of iron- Microcytic
3. impaired erythropoiesis due to marrow stem cells failure- normocytic
60
major form of B12 deficiency anemia
pernicious macrocytic anemia- results from lack of intrinsic factor resulting in malabsorption of B12
61
B12 & folate are ______ in the DNA synthetic pathway
coenzymes
| synthesis of RNA & protein are unaffected
62
to absorb B12 you need
intrinsic factor secreted by gastric parietal cells
63
vitamin B12 aka
Cobalamin- complex organometallic compound
64
_______ are the ultimate origin of cobalamin in the food chain
microorganisms
65
B12 is released from protein bound form by
pepsin in the stomach
66
free B12 binds to proteinsc called
cobalophilins or R-binders
67
________ delivers B12 to the liver & other cells in the body
transcobalamin II
68
Atrophic gastritis
loss of gastric mucosal folds & thinning of gastric mucosa with parietal cells-> no IF
69
antibodies detected in pernicious anemia
Type 1: blocks binding of B12 to IF
Type 2: block binding of IF or IF-B12 to its receptor on ileal cells
type 3: bind to the gastric proton pump on parietal cells
70
folate deficiency anemia is similar to B12 EXCEPT
NO neurological changes
71
important metabolic rxns that depend on THF
synthesis of purine, methionine, & deoxythymidylate monophosphate
72
form of folate in green veggies
folypolyglutamates
73
most common anemia world wide
iron deficiency
74
iron content in the body is distributed into:
functional(globin) & storage comparentments
75
ferritin is stored within
parenchymal cells in the liver
mononuclear phagocytic cells in spleen & bone marrow
can be found within all tissues
76
hemosiderosis
excess iron causes hemosiderin to accumulate within cells & tissues
77
in iron deficiency, plasma ferritin is always
below 12mg/L
78
in iron overload, plasma ferritin is at
high values approach 5000mg/L
79
iron is stored in
ferritin
80
iron is transported in plasma by
transferrin
81
iron absorption takes place mainly in
the duogenum
82
major function of plasma transferrin is to
deliver iron to cells
83
_____ cells have high affinity receptors for transferrin
immature RBCs
84
aplastic anemia common cause
exposure to chemicals/drugs-> suppression of multipotent myloid cells-> inadequate production of differentiated cell line
85
anemia of chronic disease
associated with < erythroid porliferation & impaired iron utilization & may mimic iron deficiency
86
common method to narrow possible cause of anemia
erythrocyte morphology- different anemias lead to different erythrocyte morphology
87
RBC indices asses:
size & Hgb content of RBCs
88
MCH (mean cell Hgb)
average amount of Hgb inside a RBCs
89
goals of treatment
alleviate signs & symptoms
correct underlying etiology
prevent complications & recurrence
90
oral iron best absorbed in the:
Fe2+ (ferrous) form
91
sickle cell syndrome:
a hereditary autosomal recessive genetic blood disorder affecting the hemoglobin beta chain
92
Sickle cell syndrome is characterized by
red blood cells that ssume an abnormal, rigid, sickle shape
93
Sickle cell syndrome results in
deformation, increased rigidity and destruction of RBCs
94
Sickle cell trait (SCT)
only one abnormal allele; usually symptomatic
95
sickle cell disease (SCD)
both alleles are mutated; develop SCA; multisystem disease associated with episodes of acute illness and progressive organ damage
96
SCD results in
impaired circulation, vasocclusive disorders, vessel damage and RB destruction; severe morbidity and early mortality
97
global distribution is indicative of two factors:
1. survival advantage in malaria-endemic regions
| 2. subsequent migrations.
98
patients with SCD experience
delayed growth (height & weight)
99
Life expectancy in SCD
males-42
| females-48
100
life expectancy in SCT
males-60
| females-68
101
it is the mutation of __ chain that accounts for the disease
beta
102
HgbS
Glutamic acid->valine(hydrophobic) at 6th AA
| alters conformational structure of hgb
103
HgbC
substitution of glutamic acid with lysine
104
val6 of beta 2 chain in one HGS forms hydrophobic bonds with
Phe85 and Leu88 of second HbS beta-1 chain
105
solubility od deoxygenated HgS is ____ than HbA
Substantially lower
106
life span of sickled RBC
10-20 days
107
3 main problems are primarily responsible for the clinical manifestation of the disease:
1. impaired circulation
2. destruction of RBCs
3. stasis of blood flow
108
factors promoting HbS polymerization
```
low pO2/hypoxia (high altitudes)
increased CO2, low pH (physical inactivity)
increased 2-3BPG in RBC
high [HgS]
low [HgF]
```
109
HgF
has gamma chains instead of beta, so no sickling
| gamma globin chains bind HgS & inhibit HgS polymerization
110
hallmarks of SCD
microvascular vasoocclusion, inflammation, system disease
111
acute complications (sickle cell crisis)
vasoocclusive, splenic sequestration, aplastic, hemolytic
112
vasoocclusive pain crisis
hand & food syndrome (dactylitis- sausage digit)- infancy
joint and extremities
abdomen
hepatic- older pts
113
splenic sequestration crisis
splenic sinusoidal vaso-occlusion-> splenic sequestration -> acute splenomegaly & decreased circulating blood volume-> hypotension & shock/death
114
aplastic crisis
destruction of erythroid precursors in marrow-> anemia
low reticulocyte count
associated with paravirus B19, strep pneumo, salmonella, & H. influenzae
115
hemolytic crisis
particulary common in pts w/ G6PDH deficiency too
acute accelerated decrease in hemoglobin level & RBCs
transfusions are necessary
116
second most common complication of SCD & most common cause of death in adult patients
acute chest syndrome
117
SCD treatment
```
lifelong multidisciplinary
pain control
infection prophylaxis
chronic transfusion therapy
preventative therapies (HgF inducers)
curative treatment (allogeneic stem cell transplantation)
investigative therapies (gene therapy)
```
118
hydroyurea
HgF inducer
inhibits production of deoxynucleotides via the inhibition of ribonucleotide reductase
can prevent painful crisis
induces proliferation of early erythroid progenitors & increase NO levels
antioxidant properties
119
hydroxyurea decreases
frequency of acute chest syndrome, hospitalization, need for transfusion, morbidity & mortality
120
hydroxyurea is a possible alternative to:
chronic transfusion to decrease recurrent stroke
121
hydroxyurea side effects
significant bone marrow toxicity- leukopenia & thrombocytopenia
drowsiness, N/V/D, constipation, alopecia, abnormal liver enzymes, creatinine & BUN
122
sodium butyrate
naturally occurring short-chain fatty acids
inhibits histone deacetylation
shown to heal leg ulcers
123
decitabine
inhibits DNA methylation (prevents gamma->beta chain)
124
only therapy offering curative potential for SCD
allogenic hematopoietic stem cell transplanation
125
gene therapy in SCD
transfer of anti-sickling beta-globin genes
| HIV lentiviral- mediated gene transfer can potentially correct hematological defects & organ damage
