L11&L12: RBCs and Hemostasis Flashcards
1
Q
what are the 3 layers you get when you centrifuge blood
A
plasma (55% on average buffy coat (WBCs, thin) formed elements (45%avg RBCs,platelets,etc)
2
Q
hematocrit =
A
RBC vol / total blood vol
or
formed element vol
total vol
3
Q
T/F men have a slightly higher hematocrit than women on average
A
true
4
Q
RBC function
platelet function
WBC function
A
gags exchange
hemostasis
defense
5
Q
what is the composition of plasma:
% H2O
% proteins
% solutes
A
91% H2O
7%prots (55%albumin,42%glob,3%fibrinogen)
2% solutes
6
Q
what is the most prevalent protein in plasma?
A
albumin (55% of protein content)
7
Q
do plasma proteins cross endothelial membrane?
A
no, too large
8
Q
the bulk of the formed elements in blood are
A
RBCs
9
Q
why is RBC biconcave disk shaped
A
- decrease O2 diffusion distance to Hb
- increase surface area/volume for gas exchange
- flexibility so it has room to bend and stretch through capillaries
10
Q
what happens if an RBC is depleted of ATP
A
it crenates (ATP plays a role in maintenence of shape)
11
Q
how does RBC make ATP?
A
glycolysis
no mitochondria
12
Q
what determines RBC type?
A
membrane glycosylations = antigens
13
Q
what is ATP used for in an RBC?
A
“ATP powers pumps”
- Ca++ ATPase pump out
- Na/K pump
14
Q
what happens if an RBC Ca++ ATPase pump is defective?
A
get kynocytes (RBCs with spicules) because high Ca++ triggers protein linkages
15
Q
what is spectrins role in an RBC?
A
forms a cytoskeletal meshowrk along inner membrane and maintains cell cell shape
-spectrin defects lead to fragile spherocytes
16
Q
RBC defects in spectrin result in…
A
fragile spherocytes
17
Q
how does Hb maintain RBC cell shape?
A
it is packed to very high density, defects / mutations, like HbS can lead to aggreagation, sickling, deformation
18
Q
3 things that maintain RBC cell shape
A
- ATP (Na/K pump)
- spectrin (or else spherocytosis)
- Hb (HbS can sickle)
19
Q
why is Hb contained within RBCs not just transported in plasma?
A
- would be oxidized and broken down very quickly in plasma
- would also change oncotic pressure of plasma drastically
20
Q
how does the RBC prevent Hb oxidation?
A
2 ways:
- metHb reductase reduces metHb back to Hb using NADPH
- contains reduced glutathione GSH, which is oxidized to GSSG to spare Hb (NADPH needed to reduce again)
21
Q
what is the equation for the reaction catalyzed by metHB reductase in the RBC
A
metHb reductase
HbFe3+ + NADH -> HbFe + NAD
22
Q
what are 2 reactions that spare Hb oxidation in RBCs?
A
metHb reductase
HbFe3+ + NADH -> HbFe + NAD
H2O2 + GSH -> GSSH + H2O
<-
glutathione reductase + NADPH
23
Q
what are 2 key enzymes that prevent Hb oxidation in RBCs?
A
- metHb reductase (reduces metHb with NADH)
- glutathione reductase (reduces GSSH to GSH with NADPH so that GSH will be oxidized before Hb is)
24
Q
how does the RBC generate its NADPH that it uses for glutathione reductase to prevent Hb oxidation?
A
NADH generated by
G6PD
glucose-6-phosphate dehydrogenase
which functions in glycolysis
25
what happens to an RBC with reduced G6PD glucose6phosphate dehydrogenase activity?
- glycolysis inhibited
- NADPH generation inhibited
- glutathione reductase inhibited
- less GSH
- more Hb will be oxidized to metHb
- hemolysis
- blood in urine
26
T/F glucose uptake in RBCs is insulin dependent, just like in most other tissues
false
| not insulin dependent
27
where does RBC formation occur...
- in embryo?
- 3rd trimester and while young?
- adult?
- yolk sac
- marrow cavities
- axial marrow cavities (distal long bones are infiltrated with fat)
28
2 precursers to mature RBC
- normoblast (differentiates 4 times over the course of 4-5 days before extruding nucleus)
- reticulocyte (enters circulation, contains residual RNA for 1-2 days then protein machinery is degraded and becomes adult RBC)
29
how many blood cells in circulation are reticulocytes?
1-2%
| they stay in circulation with RNA 1-2 days before maturing completely, RBCs live 120 days, 2/120 = 1-2%)
30
how can RBC production be increased?
in response to low pO2, endocrine mostly in the kidney produce erythropoietin, a hormone that stimulates size of erythroid marrow compartment and rate of erythrocyte precursor maturation
31
what stimulates erythropoietin production?
anything that decreases pO2
32
what does erythropoietin do?
hormone that stimulates size of erythroid marrow compartment and rate of erythrocyte precursor maturation (produce more RBCs)
33
where does Fe++ for heme synthesis come from?
mostly recycled from old Hb, small amount obtained through diet, mobilized body stores
34
how is Fe++ transported into the normoblast?
binds to transferrin receptor and endocytosed
| transferrin receptor eventually re-incorporated into the membrane
35
what does a transferrin receptor do?
binds to Fe++ and endoycytosis to bring it into RBC
| transferrin receptor eventually re-incorporated into the membrane
36
what is ferritin
storage form of Fe++ in RBC
37
what is the storage form of Fe++ in the RBC
bound to ferritin
or
bound to hemosiderin
38
what indicates aging of RBC?
not entirely clear... seems to be membrane changes... spleen tests flexibility
39
T/F Fe++ is endocytosed with the tranferrin receptor into the mature RBC for heme / Hb snthesis
false
| normoblast
40
how long is an RBC in circulation
120 days
41
where does RBC breakdown occur?
reticular endothelial cells of the spleen
| some liver
42
how does the spleen detect RBC aging?
RBC must be very flexible to squeeze through reticular endothelial cells of spleen so probably tests membrane flexibility for membrane changes
43
what is the treatment for spherocytosis
splenectomy
| keep spleen from degrading too many cells, liver will continue to remove RBCs from circulation
44
is the porphyrin ring of heme recycled?
no
45
T/F the α-carbon of the porphyrin ring in heme produces carbon monoxide CO upon RBC breakdown
true
46
icterus and jaundice are signs of...
hyperbilirubinemias
47
what is the fate of Hb in plasma after hemolysis?
2 possible paths:
- broken into dimers, bound by haptoglobin, pulled in by liver & broken down (if haptoglobin capacity is exceeded, Hb appears in urine)
- oxidized to metHb, broken down by macrophage and aa's recycled
48
what is the protein that binds to Hb dimers in the blood after hemolysis and facilitates their transport into the liver?
haptoglobin
49
what is haptoglobin's role in hemolysis?
binds free floating Hb dimers and brings them into liver for breakdown
50
what happens to Fe after hemolysis?
bound to transferrin and brought into marrow for recycling (mostly)
51
hemoglobinuria
Hb in the urine
52
what protein levels in plasma can be used to diagnose an intravascular hemolytic event?
serum haptoglobin levels
will be decreased for a time following a hemolytic event because will be bound to Hb dimers to bring them to liver for degradation
53
why higher Fe intake for women necessary?
menstrual blood loss
54
the majority of anemias are __
hypoproliferative
| synthesis of Hb or RBCs too slow
55
anemia is defined in 2 ways:
- insufficient RBCs
| - insufficient Hb
56
-hypoproliferation
-iron deficiency
-acute bleeding
-bacterial infeciton
-marrow damage
-erythropoietin deficiency
-hemolysis (HbS, spherocytosis, etc)
-thalassemias
-dietary difficiency (B12, folic acid)
are all possible causes of __
anemia
57
how can bacterial infection lead to anemia?
body will shut down Fe release to keep it from bacteria... with a long-term infection, FE from catalysis will not make it back to marrow for erythropoesis
58
what kind of treatment can lead to anemia from marrow damage?
chemotherapy (targets rapidly dividing cells)
| -treat with marrow transplant
59
how can you treat an anemia due to marrow damage?
marrow transplant
60
HbS and spherocytosis are both forms of...
hemolytic anemia
61
maturation abnormalities that can lead to anemias include
alpha and beta thalassemias
62
pernicious anemia is caused by
deficiency of intrinsic factor (a glycoprotein produced by parietal cells in stomach), which is needed to absorb vitamin B12
-or a deficiency of vitamin B12 itself
63
deficiency of intrinsic factor production by parietal cells in the stomach can cause...
pernicious anemia
| because intrinsic factor needed to absorb vitamin B12
64
folic acid must be obtained through the diet for....
DNA synthesis and erythropoesis
65
what are two forms of dietary anemias
- folic acid needed for DNA synthesis & erythropoesis
| - vit B12 and intrinsic factor to absorb it needed for... erythropoesis?
66
Rhogam
anti-D (Rh+) antibodies
injected into Rh- mother late in Rh+ pregnancy to bind and hide Rh+ antigens from mother's immune system and prevent developing innate anti-D antibodies for next Rh+ pregnancy
67
antibodies are like molecular staples and cause __
agglutination
68
how are RBC antibodies developed
anti-A
anti-B
anti-D
anti-A from bacterial/allergic exposure
anti-B from bacterial/allergic exposure
anti-D usually only from Rh+ pregnancy
69
this blood type is a universal receptor
AB+
70
this blood type is a universal donor
O-
71
primary hemostasis consists of...
secondary hemostasis consists of...
vasoconstriction
platelet plug formation
coagulation
72
thrombosis =
clotting where you don't want it
| opposite of hemorrhagic stroke
73
hemorrhagic stroke =
inability to clot when you want it
| opposite of thrombosis
74
3 pathways of vasoconstriction
which are quick and which are slower onset?
myogenic (quick)
neurogenic (quick)
humoral (TA2) (slow)
75
this formed element has no nucleus but many granules
platelet
76
pathway of platelet plug formation
```
collagen contact
platelet adhesion (VWF von wil factor)
release reaction (exocytose granules ADP)
membrane changes
cyclooxygenase (act on mem lips to produce)
TA2 thromboxane A2
positive feeback (TA2 and ADP)
platelet plug
```
77
how does aspirin affect platelet plug formation
blocks cyclooxygenase from reacting with membrane phospholipids to produce TA2 thromboxane A2
78
thrombocytopoenia =
not enough platelets, cannot form plugs
79
need secondary hemostasis (coagulation) because...
platelet plug not sufficient in long term (when vasoconstriction lessens will be washed away)
80
quick and dirty secondary hemostasis (coagulation)
```
prothrombin
thrombin
fibrinogen
fibrin
polymerization
fibrin stabilizing factor (cross-links)
```
81
hemophilia
deficit in clotting (thromboplastic) factors
82
2 pathways for secondary hemostasis (coagulation)
extrinsic (trigger)
| intrinsic (positive feedback)
83
extrinsic hemostasis pathway
```
tissue trauma, blood extravisation
tissue thromboplastin (factor VII) + Ca++
prothrombin activator
thrombin
triggers intrinsic pathway
```
84
intrinsic hemostasis pathway
```
trauma
protease cascade
prothrombin activator
thrombin
positive feedback
use platelet lipids for reaction surface
```
85
how is the extrinsic hemostasis pathway shut off?
TFPI tissue factor pathway inhibitor
| inhibits tissue thromboplastin
86
what are 2 very important proteins in extrinsic hemostasis pathway
- tissue thromboplastin VII (activates prothrombin cleavage)
- TFPI (inhibits tissue thromboplastin VII and shuts off pathway)
without these, severe pathology
87
how are clotting factors commonly prepared
post translational modification using vitamin K to carboxylate glutamic acid residues into γ-carboxy glutamic acid (- charges can bind Ca++ in the process of clotting)
88
T/F About 2% of red cells appearing in the blood still have their nuclei
false
| still have some RNA (reticulocytes)
89
T/F here is more hemoglobin in whole blood than all of the plasma proteins combined
true
90
T/F platelet aggregation is promoted by ADP
true
| ADP is exocytosed from platelets in the release reaction
91
TFPI
in plasma, inhibits extrinsic hemostasis pathway and brings it to and end
92
antithrombin III
binds and inhibits clotting factors
| activity increased by heparin
93
how does heparin interact with antithrombin III
heparin increases antithrombin III activity, inhibiting clotting factors
94
thrombomodulin
```
binds thrombin
changes specificity of thrombin
throbmin no longer cleaves fibrinogen
cleaves proteins C and protein S instead
shuts down coagulation
```
95
plasmin
breaks down fibrin
96
TPA tissue plasminogen factor
activates plasminogen
| plasmin breaks down fibrin
97
von willebrant's factor
helps platelet adhesion in primary hemostasis
98
TA2 thromboxane A2
- produced by cyclooxygenase reaction with membrane phospholipids
- promotes platelet aggregation with ADP
* also promotes humoral vasoconstriction*
99
what is ADPs role in primary hemostasis
exocytosed from platelets during release reaction
| -promotes platelet adhesion
