Haemoglobin, Haemostasis & its Drugs Flashcards

1
Q

The harm prosthetic group does three things:

A
  1. O2 transport
  2. Electron transport (Fe2+Fe3+)
  3. Redox rxn enzymes H2O2–>H20
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2
Q

Give me an example of a tetrapyrolle:

A

Porphyrin

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3
Q

Can Fe2+ transport O2 instead of Fe3+?

A

Yes dummy. It has to be Fe2+!

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4
Q

Fe3+’s colour looks like

A

Rust/Brown

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5
Q

What Hb is scarlet red?

A

Hb02

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6
Q

Hb itself is Blue (T/F?)

A

False: it’s dark red

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7
Q

HbCN’s colour

A

Blue

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8
Q

T/F? Hb’s affinity for CO is 300x than that of O2

A

False. Only 200x.

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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

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10
Q

Is there any carbon monoxide in your blood RIGHT NOW?!

A

Yep. 1%.

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11
Q

T/F? Kendrew and Perutz solved the structure of haemoglobin first, then myoglobin.

A

False. Myoglobin was the first.

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12
Q

Where is myoglobin found?

A

Storage for use in Muscle.

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13
Q

How are myoglobin and haemoglobin genes related?

A

Evolved from a common ancestor.

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14
Q

Haemoglobin is monomeric?

A

Nope. Tetrameric. You’re thinking of Myoglobin eh?

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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.

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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.

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17
Q

What is Myoglobin made out of?

A

75% a-helices secondary structure

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18
Q

a-helices are what handed? how many and how are they designated?

A

8 right handed from A-H

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19
Q

what is the percentage of deoxyhemoglobin in the blood?

A

15%

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20
Q

What’s so special about Foetal Hb?

A

HbF has gamma chains which are higher affinity for O2.

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21
Q

The Hb Gamma chain is a variant of which Hb subunit?

A

The Adult Hb Beta subunit.

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22
Q

What does Histidine F8 do?

A

anchors Haem group

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23
Q

What does Histidine E7 do?

A

excludes H20 from Fe2+ and lets O2 to bind

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24
Q

T/F? Oxygen pulls the iron atom out of the plane of the Haem

A

False.

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25
Q

When O2 binds, Histidine F8 is pulled too and what happens?

A

changes the tertiary structure of the whole damn subunit.

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26
Q

After one subunit changes then what?

A

The other three follow suite like lemmings. Cooperative change.

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27
Q

In oxyheme the H-bond is where?

A

between His E7 and one of the oxygens

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28
Q

in deoxyheme where is the H-bond?

A

between alpha and beta subunits

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29
Q

Explain the T-form of haem:

A

T=tense due to 8 salt bonds in deoxy-Hb

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30
Q

R form of Hb: explain!

A

R=relaxed, oxyhaemoglobin and is a relatively open structure

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31
Q

What is the deoxy state locked by?

A

Asp-Tyr H-bond

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32
Q

What is the oxystate locked by?

A

Asn-Asp H-bond

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33
Q

What the heck is BPG?

A

2,3-bisphosphoglycerate is n allosteric effector of Hb.

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34
Q

Hb at P50 is?

A

26 torr

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35
Q

1 atm is how many Torr?

A

758 mmHg

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36
Q

758 mmHg is how many kPa?

A

101

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37
Q

what is P50?

A

pressure of half saturation

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38
Q

What animal has an uncomfortable amount of myoglobin?

A

Whales.

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39
Q

What’s the second meaning of Allosteric?

A

A protein with sigmoid kinetics

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40
Q

Acid shift the curve to the?

A

Right

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41
Q

Alkalosis shifts the curve to the?

A

Left

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42
Q

How do you explain the sigmoid shape of Hb?

A

Due to cooperative binding/unbinding of O2 via the subunits.

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43
Q

What’s the Bohr effect?

A

acid stims HbO2 to yield more O2 via stabilizing the heme

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44
Q

Altitude adaptation shifts the curve to the?

A

Right.

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45
Q

How does Altitude adaptation work?

A

elevation of 2,3 BPG from 4.5mM to 7mM

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46
Q

How are red cell numbers increased?

A

kidneys release EPO

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47
Q

Foetal haemoglobin’s saturation curve shift which way?

A

Left

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48
Q

How is the other 85% of CO2 transported?

A

as bicarbonate dissolved in the blood

49
Q

Which ONE base change causes Sickle Cell?

A

Sickle Hb has a Val instead of a Glu

50
Q

Why would sickle cell be selected for in Africa?

A

Malaria can’t replicate in sickle cells.

51
Q

In Hb Hammersmith, Phe changes to Ser in Hb… so what?

A

Phe stops water from entering, Mutant Hb only lasts 14 days.

52
Q

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.

A

I’ll get back to you on that one.

53
Q

Why is coagulation in a test tube different than in your body?

A

Tube can’t replicate the endothelium and vessels.

54
Q

3 things happen in primary haemostats and it happens in seconds

A
  1. vasoconstriction
  2. platelet adhesion
  3. platelet aggregation
55
Q

2 things happen in secondary haemostats in the following minutes:

A
  1. activation of protein coagulation factors

2. Formation of Fibrin

56
Q

Why the heck would you want Fibrinolysis?

A

To make the area smooth again baby.

57
Q

Virchow’s Triad is:

A
  1. Vessel Wall
  2. blood composition
  3. Blood flow
58
Q

What’s so special about the vessel wall anyways?

A

dynamic, active, interacts with blood and tissue, can be pro or anti thrombotic.

59
Q

We have awesome new ways to test for vessel wall integrity?

A

NOT!

60
Q

What’s the ‘starter motor’ for the coagulation system?

A

Tissue Factor

61
Q

What’s the key enzyme we need to control in coagulation?

A

Thrombin.

62
Q

What happens in the initiation phase of clotting?

A

Tissue factor binds FVIIa, activates FIX and FX, then FXa binds to FVa on cell surface

63
Q

you want to convert fibrinogen to Fibrin, what’s the magic ingredient?

A

Thrombin

64
Q

what’s so important about fibrin anyways? Can’t the body be happy with a platelet plug?

A

Nope. needed to reinforce the clot

65
Q

How do you Inactivate Thrombin?

A

Thrombin binds to thrombomodulin and antithrombin

66
Q

Thrombin’s kind of an attention whore, what 3 other things does it do outside coagulation?

A
  1. Embryonic Growth
  2. tumour spread
  3. Vascular Disease
67
Q

how do you see the appearance of platelets?

A

electron microscope

68
Q

Haemophilia is a deficiency in what?

A

Factor 8 (Queen Victoria)

69
Q

Coagulation tests are finicky. You minimize error with these five things:

A
  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
Q

APTT stands for:

A

activated partial thromboplastin time

71
Q

4 global tests for bleeding

A

ACT, APTT, PT/INR, and Thrombin generation

72
Q

Pros and Cons of functional clot based Assay:

A

Pro: sorta reflects physiology better
Con: technically hard yo.

73
Q

Pros and Cons of Chromogenic assay

A

Pro: reproducible
Con: not really physiologically relevant

74
Q

Pros and Cons of Immunological assays

A

Pro: measures amount of protein
Con: not much re: functional capacity

75
Q

INR equation =

A

(patient PT/Mean normal PT)*ISI

76
Q

What is ISI?

A

International sensitivity index: how sensitive reagent is to reducing Vit K dependent factors

77
Q

Warfarin inhibits 5 things:

A
  1. Vitamin K
  2. Factor II
  3. Factor VII
  4. Factor IX
  5. Factor X
78
Q

A ‘normal’ value depends on:

A

What the normal is for their AGE range.

79
Q

what is the size of a WBC?

A

10-14 microns

80
Q

Coagulatoin in vivo is called a?

A

Thrombus

81
Q

Coagulation in vitro is called a?

A

Clot

82
Q

Define thrombosis

A

plug in vessels in absence of blood loss

83
Q

How do platelets cause initial constriction in injury?

A

ADP and 5-HT release

84
Q

How do you get from platelets to adhesion aggregation?

A
PLA2, 
Arachadonic acid
COX
TXA2
Ca2+
Adhesion aggregation
85
Q

What causes fibrinolysis?

A

Plasmin

86
Q

2 injectable anticoagulants:

A

Heparin and low weight heparin

87
Q

When is heparen used?

A

acute short term

88
Q

What is a vitamin K injection considered?

A

procoagulant drug

89
Q

how to you take warfarin?

A

orally

90
Q

what’s a long-term therapy drug for anticoagulation?

A

warfarin

91
Q

How does Heparin work?

A

enhances antithrombin III which inactivates Xa

92
Q

Heparin is small. T/F?

A

It’s huge bro. 60-100kD.

93
Q

When do you use low molecular weight Heparin

A

patient self administration @ home. longer halflife.

94
Q

What is secreted by leeches to prevent coagulation?

A

Hirudin.

95
Q

What is APTT?

A

Activated Partial Thromboplastin Time. For Heparin monitoring.

96
Q

3 adverse effects of Heparin?

A

Haemorrhage
Thrombocytopenia
Osteoporosis

97
Q

Warfarin blocks what factors via Vit. K reductase?

A

II, VII, IX, X

98
Q

Warfarin derived from?

A

Coumarin

99
Q

How fast does warfarin act?

A

no too fast, delayed onset, only in vivo

100
Q

Warfarin takes out current factor II, VII, IX, X?

A

Nope. doesn’t affect already active factors

101
Q

3 ways to reverse warfarin overdose:

A
  1. oral Vit. K
  2. I.V. vit. K
  3. fresh frozen plasma
102
Q

Why is Warfarin ‘moody’?

A
  1. rapidly absorbed
  2. depends on your diet vit.K
  3. binds strongly
  4. interacts with lots of drugs (NSAIDS, aspirin)
103
Q

Why is is bad to drink alcohol with warfarin?

A

If you drink, alcohol will outcompete the cytochrome p450 pathway in the liver and reduce warfarin clearance

104
Q

New anticoagulants target what factors?

A

Indirect factor Xa inhibitors
Direct facotr Xa inhibitors
Direct Thrombin Inhibitors

105
Q

Eg. of a newer anticoagulant drug?

A

Dagibatran (Pradaxa)

106
Q

Why are Doctors hesitant to use newer anticoagulant drugs?

A

No antidotes in case

107
Q

What is an ADP receptor antagonist?

A

Clopidogrel. affects Platelet activation/adhesion

108
Q

How does clopidogrel work?

A

prevents ADP from binding to platelet receptor. blocking glycoprotein IIb/IIIa = no platelet aggregation

109
Q

What does Aspirin bind to in platelets exactly?

A

COX - irreversibly.

110
Q

What is TXA2?

A

Thomboxane A2 inhibitor for platelet interference

111
Q

What’s another GPIIb/IIIa besides clopidogrel? when is it used?

A

Abciximab. IV, high risk acute coronary.

112
Q

What is the antiplatelet drug that is an monoclonal antibody?

A

Abciximab

113
Q

How is clopidigrel adminitered?

A

Orally. It’s a prodrug.

114
Q

What 2 drugs enhances fibrinolysis?

A
  1. streptokinase

2. alteplase

115
Q

What’s the good news and bad news with streptokinase?

A
  1. works awesomely to activate plasminogen

2. Single use due to antigenicity. :(

116
Q

What’s the expensive ass fibrolytic drug called?

A

Alteplase

117
Q

How is alteplase better than streptokinase?

A

Not antigenic

118
Q

Example of a Human recombinant tissue plasminogen with a short half life and needs IV.

A

Alteplase