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Hematopoesis Flashcards

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1
Q

TPO does what

A

stimulates BFU(EMeg)–> CFU-MEG for platelet production

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2
Q

EPO does what

A

Stimulates BFU-E->CFU-E for RBC production

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3
Q

G-CSF does what

A

stimulates CFU-GM–>CFU-G for neutrophil production

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4
Q

GM-CSF does what?

A

acts on all blast cell lines

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5
Q

Cells involved in myeloposiesis (aka granulopoiesis)

A

Monocytes, Neutrophils, Eosinophils, basophils

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6
Q

Cells involved in ertyhropoiesis

A

red blood cells

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7
Q

cells involved in thrombopoiesis

A

platelets

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8
Q

cells involved in lymphopoiesis

A

T cells, B cells, NK cells

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9
Q

Which cells are defined as blasts (<4%)

*not identifyable microscopically but by their responsiveness to growth factors

A

PSC–>CFEGEMM and common myeloid progenitor

then BFUE-CFUGM-CFUbaso
all of these are acted on by GMCSF

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10
Q

List normal maturation of granulocyte

A 
Blast-->
Promyelocyte-->
myelocyte-->
Metamyelocyte-->
bands-->
neutrophil
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11
Q

mature species outnumber younger species why?

A

because maturation is a process of DIFFERENTIATION alongside a process of DIVISION
(age=increase in rounds of division)

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12
Q

key regulator of granulopoiesis/ myelopoiesis

A

GM-CSF

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13
Q

eosinophils branch of when during myelopoiesis–>

A

between morphological bast stage and promyelocytes (in response to GM-CSF

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14
Q

G-CSF role in myelopoeisis

A

acts more specifically on neutrophil precursors

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15
Q

list the maturation of RBC’s

A 
blast-->
pronormoblast-->
basophillic erythroblast-->
polychromatophillic erythroblast-->
normochromic erythroblast
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16
Q

erythropiesis is under the control of which growth factor

A

Erythropoietin

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17
Q

EPO production is regulated by?

A

Hypoxia–> causes HIF-1 to be up-regulated which goes to nucleus and up-regulates EPO to be made and released by renal peritubular capillaries

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18
Q

renal failure can cause

A

ANEMIA: loss of EPO production and timely release

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19
Q

describe nascent RBC’s

A

–> anucleate, polychromatic reticulocytes

larger than usual, filled with RNA, so will stain with methylene blue

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20
Q

Do blasts have nuclei

A

YES

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21
Q

Pletelet maturation

A

blast–> immature megakaryocyte–> mature megakaryocyte–>platelets

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22
Q

platelet production is under control of –>

A

TPO

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23
Q

describe megakaryocytes

A

poly ploid (16-32 haploid nuclei)–> extend snake-like protoplatelets into bone marrow blood vessels

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24
Q

TPO is made in the

A

liver

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25
How does TPO work
binds megakaryocytes-->stimulates production from immature precursors and platelet production from immature megakaryocytes
26
low platelet count...
--> allows more TPO to bind megakaryocytes, stimulating more thrombopoiesis.
27
hematopoetic GFR's work via
JAK2 signal transduction | *acquired mutations here will give you cancer!
28
red cell production requirements
heme synthesis globin synthesis DNA synthesis regulation
29
heme synthesis
iron B6 succinyl Coa glycine
30
hemoglobin=
heme + globin
31
heme=
iron + protoporphyrin
32
heme synthesis also requires...
B12 and folate
33
DNA synthesis requires
1. dNTP's-->thymidine (THYMINE)-->which requires B12 and folate 2. deoxynucleotide reductase
34
proper regulation of EPO requires
healthy kidneys | normal bone marrow micro-environment
35
Iron deficieny results in-->
red cells without enough hemoglobin
36
most common cause of microcytic hypochromatic anemia
iron Deficiency anemia
37
RDW correlates with
anisocytosis
38
Characteristic but not diagnostic of Iron def. anemia
poikilocytosis and anisocytosis
39
why is free plasma iron bad
causes free radicals >would augment bacterial growth (ergo iron is low during inflammatory state and hepcidin is up)
40
gastric environment that favors iron uptake
acidic (low pH)-->therefore co-admin of Vitamin C will increase the amount of iron one takes up
41
iron is absorbed in the...
deodenum
42
b12 is absorbed in the
illuem
43
iron travels in the blood
with ternsferrin--> in the ferrous state Fe3++
44
dietary iron-->
usually Fe+++
45
iron is transported into the enterocyte via
DMT1--> in the fe++ state
46
how does fe+++/transferrin get into the bone marrow to make heme
binds to transferrin receptor in erythroid precursors in the bone marrow
47
storage form of iron
ferritin
48
where is iron stored
macrophages in the liver, spleen bone marrow
49
how does iron get from gastric lumen into enterocyte
dmt-1
50
how is heme iron absorbed
heme carrier protein 1
51
how does iron get from enterocyte to plasma
ferroportin
52
inhibitor of feroportin
hepcidin
53
how is DMT1 regulated
iron dependent regulation of its mRNA
54
hepcidin transcription is increased by
IL-6 9we dont want the bacteria to have iron
55
TIBC goes up or down in infection
down-->bind up iron making it unavailable to bacteria
56
transporter responsible for moving iron from macrophages in storage pool-->making it available in plasma for erythroid precursors
ferroportin
57
Most useful measure of iron metabolism in anemias of unknown etiology
serum ferritin | measures storage iron
58
simplest measure of transferrin-bound iron
serum iron | *but does not directly address iron stores
59
Serum ferritin is propoertional to
amount of storage pool iron in the body
60
TIBC=
total amount of transferrin in ciruclation
61
transferrin saturation
``` serum iron (transferrin bound fe)// total transferrin *tells us how active transport system is ```
62
UIBC=
TIBC-serum ferritin
63
WHen would you see an increase in Soluble Transferrin receptor?
when iron storage pool is depleted following loss of serum iron *macrophages increase the amount of transferrin receptors--> manifests as increase in sTFR-->
64
reliable indicator between anemia or chronic disease and iron deficiency anemia
sTFR will be increased in iron deficiency anemia and NOT in anemia of chronic disease
65
ferritin is an
accute phase protein and will be elevated in inflamatory states
66
markers of Iron defieincy anemia
1. increased soluble transferrin receptor 2. decreased serum ferritin 3. decreased serum iron 4. increased TIBC 5. increased ferroportin
67
normal iron/transferrin levels increase or decrease hepdicin production
increase-->which decreases ferroportin and iron uptake
68
below average iron/transferrin levels increases or decreases hepcidin production
decreases --.ferroportin is increased and more iron is absorbed
69
reduced globin production=
thalassemia
70
characters of beta thalassema
microcytic, hypochromic, with target cells (nonspecific)
71
differentiates beta thal from IDA
MCV < 70 and a NORMAL or increased NUMBER OF BLOOD CELLS
72
IDA HAS NORMAL OR REDUCED # OF RBC'S
reduced
73
confirmation of beta thal-->
hg electrophoresis
74
normal heomoglobin : HgbA
alpha2beta2
75
HgA2
alpha2delta2
76
fetal Hgb
Alpha2gamma2
77
beta thalassemia will result in which types of Hgb in the adult
over production of Hgb delta--> so increased Hgb A2
78
beta thalassemias are more susceptible to...
point mutations
79
alpha thals are more susceptible to
deletions
80
Hgb H
three deletions of alpha globin gene--> result is beta tetramers-->increased afinity for O2-->poor deivery
81
Hgb Bart;s-->
deletion of four ALPHA alleles-->result is gamma tetramer, and fetus dies
82
which alpha thal can be confused for IDA
alpha thalassemia type 3
83
Type 2 alpha thal in adulthood
>normal hgb electrophoresis as adults | >mild microcytic anemia
84
Type 2 alpha thal prenatal
excess Hgb Barts at birth
85
Dx of Thalassemia 2 trait
Pcr based (electrophresis and/or sequencing)
86
overall cause of megaloblastic anemia
inhibition of DNA synthesis
87
causes leading to megaloblastic anemia
1. pernicious anemia-->b12 def. 2. impaired folate uptake 3. drug effect (HAART and hydroxyurea) 4. Myelodysplastic syndrome
88
Most megaloblastic anemias can be dx with...
bone marrow biopsy
89
the urge to breath is regulated by Co2
co2 concentration--> not o2
90
2 overall causes of reduced circulating red cell mass
1. decreased produciton of RBC's | 2. increased loss of RBCs
91
discuss anemia of chronic inflammation
IL6 induces liver to produce--> increased hepcidin (acute phase reactant)--> decreased uptake and release from macorphages storage pool (via destrcution of ferroportin) --> erythroppiesis comes to a screeching HALT
92
normocytic anemias
1. anemia of chronic disease 2. thalassemias (sickle cell) 3. pregnancy 4. hemolysis 5. b2 or b6 defiency
93
Anemia of chronic disease will present as what? | everybody is ordered off the street
1. increased hepcidin-->ferroportin inhibited 2. therefore decreased serum iron 3. decreased transferrin 4. decreased TIBC 5. increased ferritin * iron shunted from plasma-->into storage macrophages!***
94
confirmation of anemia of CD
bone marrow biopsy
95
chronic disease that can cause anemia
cancer of any type RA TB AIDS
96
reticulocyte count with ACD and IDA
will be low--> unable to compensate | also could be an EPO problem

Haematology (7 decks)

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