Case 8 Flashcards
1
Q
what are the two clotting pathways
A
internal and external
2
Q
what are risk factors for a DVT
A
alteration in the blood flow immobilisation obesity pregnancy cancer
3
Q
what are hyper coagulable states
A
- OCP (oestrogen containing)
- Genetic thrombophilia
- factor V lieden deficiency
- Portein S and C deficency
- antithrombin deficiency
- acquired thrombophilia
- antiphospholipid syndrome
- nephrotic syndrome
- paroxysmal nocturnal haemogloburnia
- cancer/preganacy
4
Q
blood flow from leg back to heart
A
popliteal veins
greater saphenous vein
femoral vein
inferior vena cava
5
Q
what is the normal value of the alveolar arterial oxygen gradient
A
normal =2 for <40 but increases with age
A-a gradient = 3.9 (1.6)
6
Q
What is PERC
A
pulmonary embolism rule out criteria
7
Q
what is the criteria in PERC
A
- age>50
- HR>100
- SaO2 on room air >95%
- unilateral leg swelling
- haemophysis
- recent trauma or surgery
- prior DVT or PE
- hormone use - oestrogen hormone
8
Q
NICE guidelines for a suspected DVT
A
9
Q
NICE guidelines for PE
A
10
Q
what do lungs that are not perfused but still ventilated look like
A
11
Q
What is CTPA
A
computerised tomography pulmonary angiogram
12
Q
what is a perfusion scan called
A
a Q scan
13
Q
ECG examples of a PE and DVT
A
14
Q
Confirmed PE therapies
A
15
Q
why is option C there
A
because all heparins are made from pork and therefore not suitable for vegetarians and muslims
16
Q
what is thrombosis
A
the formation of a solid or semi-solid mass from the constituents of the blood while moving within the vascular system during life
17
Q
what is an embolism
A
the transport of abnormal material by the blood stream and its impact on a blood vessel
18
Q
what is a clot
A
a solid mass formed from the constituents of the blood that no longer moves
19
Q
where may thrombi form in the heart
A
the lumen of the heart
echocardiogram shows thrombi attached to walls of left ventricle after MI
20
Q
What can an arterial thrombi cause
A
ischaemia and embolism to the leg
21
Q
what are the lines of Zahn in veins
A
alternating laters of platelets and erythrocytes
22
Q
what is virchows triad
A
factors that promote thrombosis
23
Q
what are the three constituents of VT
A
- abnormalities to the vessel wall
- abnormalities of the blood flow
3, abnormalities of the blood constituents
24
Q
what causes abnormalities of the vessel wall in arteries
A
atheroma
inflammation
atherosclerotic plague
25
what causes abnormalities of the vessel wall in the heart
myocardial infarction - scarring and sites of immobility
rheumatic endocarditis
contribution of breakdown of dead muscle
26
what causes abnormalities of the vessel wall in the veins
trauma
inflammation
chemicals
27
what chemicals can disrupt the vessel wall in veins
scelerosants: irritant substances injected to induce thrombophlebitis and hence obliterate varicose veins
glucose: atheroma in diabetes mellitus
28
abnormalities of blood flow in the arteries
turbulence
aneurysms, plaques and spasm
(aneurysms are filled with thrombus)
29
What are abnormalities of blood flow in the heart
arterial fibrillation - becomes dilated and flow is limited
aneurysms
30
what causes abnormalities of blood flow in veins
- compression from plaster casts
- inactivity, postoperative bed rest
- economy class syndrome from airplanes
- heart failure
- circulatory shock
31
abnormalities of blood constituents
- increased viscosity
- polycythemia
- dehydration
- chronic hypoxia
- polycythemia ruba vera
- hyperproteinaemia
- multiple myeloma (tumour is plasma cells in bone marrow with accumulation of immunoglobulins in plasma)
32
abnormalities in clotting
- pregnancy (mother does not bleed when placenta detaches)
- some contraceptive pills
- following trauma
- thrombocythemia
- tumours
- inherited
33
most common fate of thrombi
resolution - fibrinolysis
34
what is the organisation fate of thrombi
- incorporation into a scar by macrophages and fibroblasts. vessel lumen remains narrowed or occulded
- intimal cell proliferation, capillary invasion and recanlisation which may restore patency
35
what is the detachment fate of thrombi
thromboembolism
36
what is a fat emboli
patients with multiple bone fractures get a fat emboli in pulmonary alveolar capillaries
petechial haemorrhages in the brain die to fat emboli following bone fracutres
when fat enters the blood stream
37
what is a gas emboli due to
- infusions
- vascular surgery
- Caisson disease: on ascending too rapidly bubbles of N2 form in the blood stream and cause the pain known as 'the bends' - divers
38
what are the pathological consequences of pulmonary embolism
```
nothing
pain that is often pleuritic
haemoptysis
breathlessness
right sided heart failure
pulmonary hypertension
sudden death
```
39
What are the 5 main components of haemostasis
1. blood vessels - vascular spasm
2. platelets - platelet plug formation
3. coagulation factors - coagulation phase
4. coagulation inhibitors - coagulation phase
5. fibrinolysis - breakdown of the clot
40
what is secreted to prevent thrombus formation
- nitric oxide - vasodilator and inhibits platelet activation and aggregation
- endothelia - vasoconstrictor
- prostacyclin - inhibits platelet activation
41
what is expressed to prevent thrombus formation
- heparin sulfate - activates antithrombin
| - thrombomodulin - changes thrombin affinity from pro clotting to anticoagulant factors
42
vessel injury diagram
43
what is the most immediate protection against blood loss
vasoconstriction
44
how long do effects of vasoconstriction last for as first defence
few seconds - minute
45
what is a chemical vasoconstrictor
serotonin - activated platelets release chemical vasoconstrictors for example serotonin
46
where are platelets produced
in the bone marrow
47
what are platelets fragments of
megakaryocytic cytoplasm
48
how many platelets can 1 megakaryocyte produce
4000 platelets
49
how large are platelets
2-4um
50
what is production of platelets stimulated by
thrombopoietin
51
where is thrombopoietin produced
in the liver
52
what does thrombopoetien do
helps to control platelet numbers
53
what is the lifespan of platelets
8-9 days
54
how long does platelet production take
around 7 days
55
how many times a year can you donate platelets
24 times a year
56
diagram on platelet production
57
what is the ratio of RBC:PLATELETS:WBC
700:40:1
58
platelet plug formation
1. normal platelets flowing in blood
2. platelets adhere to damaged endothelium and undergo activation
3. aggregation of platelets into a thrombus
59
what is in the cytoplasm of an activated platelet
1. contractile proteins: actin and myosin and thrombosthenin
2. residuals of both the endoplasmic reticulum and the Golgi apparatus that synthesis various enzymes and especially store large quantities of calcium ions
3. mitochondria capable of forming ATP and ADP
4. enzyme xystemsn that synthesise prostaglandins
5. fibrin stabilising factor
6. a growth factor that causes cell growth
60
what does the cell membrane of activated platelets contain
1. glycoproteins
- these repulse adherence to normal endothelium
- instead they cause adherence to injured areas of the vessel wall, especially to injured endothelial cells and even more to exposed collagen from deep within the vessel wall
2. phospholipids
- these are present in large amounts
- these activate multiple stages in the blood clotting process
61
what are the three stages of platelet plug formation
1. adhesion and activation
2. secretion and release
3. aggregation
62
characteristics of platelets when they come into contract with damaged vascular surface
- they begin to swell
- they assume irregular forms with numerous irritating pseudopods protruding from their surface
- their contractile proteins contract forcefully and cause the release of granules that contain multiple active factord
63
what do platelets adhere to in tissues
adhere to collagen and to protein called von Willebrand factor that leaks into the tissue from the plasma
64
what is the protein found on cell membrane of platelets that adheres to the collagen
Glycoprotein Ib
65
what does glycoprotein Ib bind to
vWF
66
what also binds to vWF
glycoproteins IIb and IIIa adhere
67
what does the vWF act as
a bridge between platelet surface receptors and exposed collagen
68
how does glyocportein Ia bind to collagen
directly no vWF
69
Platelet adhesion diagram
70
what does prostaglandin synthesis activate
production of thromboxane A2
71
what do ADP and thromboxane A2 induce
additional platelet aggregation through
- activated platelets secrete serotonin which increase vasoconstriction
- activated and damaged endothelial cells secrete endothelin causing vasoconstriction
- this cascade effect of activated platelets forms the platelet plug
72
what is a blood clot composed of
- a meshwork of fibrin fibres ruling in all directions and entrapping blood cells
- platelets
- plasma
73
what are the two courses a clot can follow
1. it can be invaded by fibroblasts which will subsequently form connective tissue through the clot
2. it can dissolve
74
what breaks down a clot
1. prostacyclin acts as an enzyme to dissolve the clot
| 2. the breakdown product of fibrinolysis - D dimer
75
what substances cause or affect blood coagulation in the blood and tissues
1. procoagulant factors: promote coagulation
2, anticoagulant factors: inhibit coagulation
3. co-factors: these aid blood coagulation
76
what does the blood coagulating depend on
the balance between the coagulate and anticoagulant factors
77
examples of a coagulation factors known by their description name :
1. tissue factor - TF/FIII
| 2. prothrombin - FII
78
examples of coagulation factors known by their factor number:
- Factor VIIII (FVIII is associated with haemophilia A)
| - Factor IX (FIX associated with haemophilia B)
79
where are most coagulation/anticoagulation/co-factors produced
the liver
80
2 substances that play a minor role in blood coagulation
- high molecular weight kiniogen (HMWK)
| - prekallikrein
81
what are these substances active to
kininogen and kvllikrein
82
general mechanism of blood coagulation
1. prothrombin activator is formed from the extrinsic/intrinsic pathway
2. prothrombin activator, in the presence of Ca2+ converts prothrombin to thrombin
3. thrombin causes polymerisation of fibrinogen molecules into fibrin fibres
83
what do platelets convert prothrombin into
thrombin because much of the prothrombin first attaches to prothrombin receptors on the platelets already bound to the damaged tissue
84
what is required by the liver for normal formation of prothrombin
Vitamin K
85
steps of the extrinsic pathway
1. traumatised tissue released tissue factor TF - a complex of phospholipids and a lipoprotein
2. TF activates FVII into FVIIa
3. TF and FVIIa together under the influence of Ca2+ ions activate FX to form FXa
4. FXa combines with phospholipids and FV under the influence of Ca2+ to form prothrombin activator
86
what activates Factor V
in the precedes of Ca2+, prothrombin spilts to from thrombin.
At first, the Factor V in the prothrombin activator complex is inactive, but once clotting begins and thrombin begins to form, the proteolytic action of the thrombin activates Factor V
87
what is the final prothrombin activator complex:
- FXa and FV
88
what causes the splitting of prothrombin to form thrombin
FXa
89
what does FV do
greatly accelerates the splitting of prothrombin
90
extrinsic pathway diagram
91
Step 1 of the intrinsic pathway
trauma to the blood alters two important clotting factors in the blood
92
what are the two clotting factors In blood in intrinsic pathway
XII and the platelets
93
what happens when XII is disturbed
forms XIIa
94
what lipoprotein does platelet phosopholid contain
platelet factor 3
95
step 2 the intrinsic pathway
the XIIa acts enzymatically activating factor XI to form XIa
- this reaction also requires HMWK and is accelerated by prekalikrein
96
step 3 of intrinsic pathway
XIa then activates Factor IX to IXa under influence of Ca2+
97
step 4 in intrinsic pathway
IXa acting with VIIIIa and with the platelet phospholipids and factor 3 active factor X into Xa under influence of Ca2+
- when either Factor VIII or platelets are short in supply, this step is defiecnt
98
step 5 of intrinsic pathway
Xa combines with V and phospholipids to form prothrombin activator under the influence of Ca2+
99
intrinsic pathway diagram
100
what is thrombin
protein enzyme that removes four peptides from each molecule of fibrinogen forming a molecule of fibrinogen monomer which under the influence of Ca2+ polymerises with other fibrin monomers forming fibrin fibres
101
what does the fibrin stabilising factor activated by thrombin in the platelets do
acts as an enzyme forming covalent bonds between the fibrin monomers as well as cross linkage between adjacent fibrin fibres
102
diagram of whole coagulation cascade
