Haemoglobin, Haemostasis & its Drugs Flashcards
1
Q
The harm prosthetic group does three things:
A
- O2 transport
- Electron transport (Fe2+Fe3+)
- Redox rxn enzymes H2O2–>H20
2
Q
Give me an example of a tetrapyrolle:
A
Porphyrin
3
Q
Can Fe2+ transport O2 instead of Fe3+?
A
Yes dummy. It has to be Fe2+!
4
Q
Fe3+’s colour looks like
A
Rust/Brown
5
Q
What Hb is scarlet red?
A
Hb02
6
Q
Hb itself is Blue (T/F?)
A
False: it’s dark red
7
Q
HbCN’s colour
A
Blue
8
Q
T/F? Hb’s affinity for CO is 300x than that of O2
A
False. Only 200x.
9
Q
Old meat and dried blood looks dark brown. Why?
A
Because Fe2+ lost an electron, got oxidized and is now Fe3+ which is brown looking
10
Q
Is there any carbon monoxide in your blood RIGHT NOW?!
A
Yep. 1%.
11
Q
T/F? Kendrew and Perutz solved the structure of haemoglobin first, then myoglobin.
A
False. Myoglobin was the first.
12
Q
Where is myoglobin found?
A
Storage for use in Muscle.
13
Q
How are myoglobin and haemoglobin genes related?
A
Evolved from a common ancestor.
14
Q
Haemoglobin is monomeric?
A
Nope. Tetrameric. You’re thinking of Myoglobin eh?
15
Q
I take out Fe2+ and replace it with Mg2+, what organism am I and what do I with my shiny Mg2+?
A
Plants. Photosynthesis.
16
Q
Why are Mb and Hb water soluble?
A
So proteins won’t precipitate in high concentration in your cells and ruin your whole day.
17
Q
What is Myoglobin made out of?
A
75% a-helices secondary structure
18
Q
a-helices are what handed? how many and how are they designated?
A
8 right handed from A-H
19
Q
what is the percentage of deoxyhemoglobin in the blood?
A
15%
20
Q
What’s so special about Foetal Hb?
A
HbF has gamma chains which are higher affinity for O2.
21
Q
The Hb Gamma chain is a variant of which Hb subunit?
A
The Adult Hb Beta subunit.
22
Q
What does Histidine F8 do?
A
anchors Haem group
23
Q
What does Histidine E7 do?
A
excludes H20 from Fe2+ and lets O2 to bind
24
Q
T/F? Oxygen pulls the iron atom out of the plane of the Haem
A
False.
25
When O2 binds, Histidine F8 is pulled too and what happens?
changes the tertiary structure of the whole damn subunit.
26
After one subunit changes then what?
The other three follow suite like lemmings. Cooperative change.
27
In oxyheme the H-bond is where?
between His E7 and one of the oxygens
28
in deoxyheme where is the H-bond?
between alpha and beta subunits
29
Explain the T-form of haem:
T=tense due to 8 salt bonds in deoxy-Hb
30
R form of Hb: explain!
R=relaxed, oxyhaemoglobin and is a relatively open structure
31
What is the deoxy state locked by?
Asp-Tyr H-bond
32
What is the oxystate locked by?
Asn-Asp H-bond
33
What the heck is BPG?
2,3-bisphosphoglycerate is n allosteric effector of Hb.
34
Hb at P50 is?
26 torr
35
1 atm is how many Torr?
758 mmHg
36
758 mmHg is how many kPa?
101
37
what is P50?
pressure of half saturation
38
What animal has an uncomfortable amount of myoglobin?
Whales.
39
What's the second meaning of Allosteric?
A protein with sigmoid kinetics
40
Acid shift the curve to the?
Right
41
Alkalosis shifts the curve to the?
Left
42
How do you explain the sigmoid shape of Hb?
Due to cooperative binding/unbinding of O2 via the subunits.
43
What's the Bohr effect?
acid stims HbO2 to yield more O2 via stabilizing the heme
44
Altitude adaptation shifts the curve to the?
Right.
45
How does Altitude adaptation work?
elevation of 2,3 BPG from 4.5mM to 7mM
46
How are red cell numbers increased?
kidneys release EPO
47
Foetal haemoglobin's saturation curve shift which way?
Left
48
How is the other 85% of CO2 transported?
as bicarbonate dissolved in the blood
49
Which ONE base change causes Sickle Cell?
Sickle Hb has a Val instead of a Glu
50
Why would sickle cell be selected for in Africa?
Malaria can't replicate in sickle cells.
51
In Hb Hammersmith, Phe changes to Ser in Hb... so what?
Phe stops water from entering, Mutant Hb only lasts 14 days.
52
With respect to haemoglobin function select the one CORRECT
statement.
1. Histidine E7 is permanently coordinated to Fe2+ in Hb.
2. The properties of Hb are independent of cellular 2,3-
bisphophoglycerate concentrations.
3. The subunits in Hb are identical (a homo-tetramer).
4. Typically 90% of oxygen carried by Hb is used by resting
tissues.
5. The Bohr effect would be diminished if Histidine was not
the amino acid at Beta residue 146.
I'll get back to you on that one.
53
Why is coagulation in a test tube different than in your body?
Tube can't replicate the endothelium and vessels.
54
3 things happen in primary haemostats and it happens in seconds
1. vasoconstriction
2. platelet adhesion
3. platelet aggregation
55
2 things happen in secondary haemostats in the following minutes:
1. activation of protein coagulation factors
| 2. Formation of Fibrin
56
Why the heck would you want Fibrinolysis?
To make the area smooth again baby.
57
Virchow's Triad is:
1. Vessel Wall
2. blood composition
3. Blood flow
58
What's so special about the vessel wall anyways?
dynamic, active, interacts with blood and tissue, can be pro or anti thrombotic.
59
We have awesome new ways to test for vessel wall integrity?
NOT!
60
What's the 'starter motor' for the coagulation system?
Tissue Factor
61
What's the key enzyme we need to control in coagulation?
Thrombin.
62
What happens in the initiation phase of clotting?
Tissue factor binds FVIIa, activates FIX and FX, then FXa binds to FVa on cell surface
63
you want to convert fibrinogen to Fibrin, what's the magic ingredient?
Thrombin
64
what's so important about fibrin anyways? Can't the body be happy with a platelet plug?
Nope. needed to reinforce the clot
65
How do you Inactivate Thrombin?
Thrombin binds to thrombomodulin and antithrombin
66
Thrombin's kind of an attention whore, what 3 other things does it do outside coagulation?
1. Embryonic Growth
2. tumour spread
3. Vascular Disease
67
how do you see the appearance of platelets?
electron microscope
68
Haemophilia is a deficiency in what?
Factor 8 (Queen Victoria)
69
Coagulation tests are finicky. You minimize error with these five things:
1. Sample should be fill to the right line.
2. standard curve
3. multiple samples
4. duplicate tests
5. multiple sessions in different time intervals
70
APTT stands for:
activated partial thromboplastin time
71
4 global tests for bleeding
ACT, APTT, PT/INR, and Thrombin generation
72
Pros and Cons of functional clot based Assay:
Pro: sorta reflects physiology better
Con: technically hard yo.
73
Pros and Cons of Chromogenic assay
Pro: reproducible
Con: not really physiologically relevant
74
Pros and Cons of Immunological assays
Pro: measures amount of protein
Con: not much re: functional capacity
75
INR equation =
(patient PT/Mean normal PT)*ISI
76
What is ISI?
International sensitivity index: how sensitive reagent is to reducing Vit K dependent factors
77
Warfarin inhibits 5 things:
1. Vitamin K
2. Factor II
3. Factor VII
4. Factor IX
5. Factor X
78
A 'normal' value depends on:
What the normal is for their AGE range.
79
what is the size of a WBC?
10-14 microns
80
Coagulatoin in vivo is called a?
Thrombus
81
Coagulation in vitro is called a?
Clot
82
Define thrombosis
plug in vessels in absence of blood loss
83
How do platelets cause initial constriction in injury?
ADP and 5-HT release
84
How do you get from platelets to adhesion aggregation?
```
PLA2,
Arachadonic acid
COX
TXA2
Ca2+
Adhesion aggregation
```
85
What causes fibrinolysis?
Plasmin
86
2 injectable anticoagulants:
Heparin and low weight heparin
87
When is heparen used?
acute short term
88
What is a vitamin K injection considered?
procoagulant drug
89
how to you take warfarin?
orally
90
what's a long-term therapy drug for anticoagulation?
warfarin
91
How does Heparin work?
enhances antithrombin III which inactivates Xa
92
Heparin is small. T/F?
It's huge bro. 60-100kD.
93
When do you use low molecular weight Heparin
patient self administration @ home. longer halflife.
94
What is secreted by leeches to prevent coagulation?
Hirudin.
95
What is APTT?
Activated Partial Thromboplastin Time. For Heparin monitoring.
96
3 adverse effects of Heparin?
Haemorrhage
Thrombocytopenia
Osteoporosis
97
Warfarin blocks what factors via Vit. K reductase?
II, VII, IX, X
98
Warfarin derived from?
Coumarin
99
How fast does warfarin act?
no too fast, delayed onset, only in vivo
100
Warfarin takes out current factor II, VII, IX, X?
Nope. doesn't affect already active factors
101
3 ways to reverse warfarin overdose:
1. oral Vit. K
2. I.V. vit. K
3. fresh frozen plasma
102
Why is Warfarin 'moody'?
1. rapidly absorbed
2. depends on your diet vit.K
3. binds strongly
4. interacts with lots of drugs (NSAIDS, aspirin)
103
Why is is bad to drink alcohol with warfarin?
If you drink, alcohol will outcompete the cytochrome p450 pathway in the liver and reduce warfarin clearance
104
New anticoagulants target what factors?
Indirect factor Xa inhibitors
Direct facotr Xa inhibitors
Direct Thrombin Inhibitors
105
Eg. of a newer anticoagulant drug?
Dagibatran (Pradaxa)
106
Why are Doctors hesitant to use newer anticoagulant drugs?
No antidotes in case
107
What is an ADP receptor antagonist?
Clopidogrel. affects Platelet activation/adhesion
108
How does clopidogrel work?
prevents ADP from binding to platelet receptor. blocking glycoprotein IIb/IIIa = no platelet aggregation
109
What does Aspirin bind to in platelets exactly?
COX - irreversibly.
110
What is TXA2?
Thomboxane A2 inhibitor for platelet interference
111
What's another GPIIb/IIIa besides clopidogrel? when is it used?
Abciximab. IV, high risk acute coronary.
112
What is the antiplatelet drug that is an monoclonal antibody?
Abciximab
113
How is clopidigrel adminitered?
Orally. It's a prodrug.
114
What 2 drugs enhances fibrinolysis?
1. streptokinase
| 2. alteplase
115
What's the good news and bad news with streptokinase?
1. works awesomely to activate plasminogen
| 2. Single use due to antigenicity. :(
116
What's the expensive ass fibrolytic drug called?
Alteplase
117
How is alteplase better than streptokinase?
Not antigenic
118
Example of a Human recombinant tissue plasminogen with a short half life and needs IV.
Alteplase
