Case 8 Flashcards
what are the two clotting pathways
internal and external
what are risk factors for a DVT
alteration in the blood flow immobilisation obesity pregnancy cancer
what are hyper coagulable states
- 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
blood flow from leg back to heart
popliteal veins
greater saphenous vein
femoral vein
inferior vena cava
what is the normal value of the alveolar arterial oxygen gradient
normal =2 for <40 but increases with age
A-a gradient = 3.9 (1.6)
What is PERC
pulmonary embolism rule out criteria
what is the criteria in PERC
- 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
NICE guidelines for a suspected DVT
NICE guidelines for PE
what do lungs that are not perfused but still ventilated look like
What is CTPA
computerised tomography pulmonary angiogram
what is a perfusion scan called
a Q scan
ECG examples of a PE and DVT
Confirmed PE therapies
why is option C there
because all heparins are made from pork and therefore not suitable for vegetarians and muslims
what is thrombosis
the formation of a solid or semi-solid mass from the constituents of the blood while moving within the vascular system during life
what is an embolism
the transport of abnormal material by the blood stream and its impact on a blood vessel
what is a clot
a solid mass formed from the constituents of the blood that no longer moves
where may thrombi form in the heart
the lumen of the heart
echocardiogram shows thrombi attached to walls of left ventricle after MI
What can an arterial thrombi cause
ischaemia and embolism to the leg
what are the lines of Zahn in veins
alternating laters of platelets and erythrocytes
what is virchows triad
factors that promote thrombosis
what are the three constituents of VT
- abnormalities to the vessel wall
- abnormalities of the blood flow
3, abnormalities of the blood constituents
what causes abnormalities of the vessel wall in arteries
atheroma
inflammation
atherosclerotic plague
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
what causes abnormalities of the vessel wall in the veins
trauma
inflammation
chemicals
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
abnormalities of blood flow in the arteries
turbulence
aneurysms, plaques and spasm
(aneurysms are filled with thrombus)
What are abnormalities of blood flow in the heart
arterial fibrillation - becomes dilated and flow is limited
aneurysms
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
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)
abnormalities in clotting
- pregnancy (mother does not bleed when placenta detaches)
- some contraceptive pills
- following trauma
- thrombocythemia
- tumours
- inherited
most common fate of thrombi
resolution - fibrinolysis
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
what is the detachment fate of thrombi
thromboembolism
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
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
what are the pathological consequences of pulmonary embolism
nothing pain that is often pleuritic haemoptysis breathlessness right sided heart failure pulmonary hypertension sudden death
What are the 5 main components of haemostasis
- blood vessels - vascular spasm
- platelets - platelet plug formation
- coagulation factors - coagulation phase
- coagulation inhibitors - coagulation phase
- fibrinolysis - breakdown of the clot
what is secreted to prevent thrombus formation
- nitric oxide - vasodilator and inhibits platelet activation and aggregation
- endothelia - vasoconstrictor
- prostacyclin - inhibits platelet activation
what is expressed to prevent thrombus formation
- heparin sulfate - activates antithrombin
- thrombomodulin - changes thrombin affinity from pro clotting to anticoagulant factors
vessel injury diagram
what is the most immediate protection against blood loss
vasoconstriction
how long do effects of vasoconstriction last for as first defence
few seconds - minute
what is a chemical vasoconstrictor
serotonin - activated platelets release chemical vasoconstrictors for example serotonin
where are platelets produced
in the bone marrow
what are platelets fragments of
megakaryocytic cytoplasm
how many platelets can 1 megakaryocyte produce
4000 platelets
how large are platelets
2-4um
what is production of platelets stimulated by
thrombopoietin
where is thrombopoietin produced
in the liver
what does thrombopoetien do
helps to control platelet numbers
what is the lifespan of platelets
8-9 days
how long does platelet production take
around 7 days
how many times a year can you donate platelets
24 times a year
diagram on platelet production
what is the ratio of RBC:PLATELETS:WBC
700:40:1
platelet plug formation
- normal platelets flowing in blood
- platelets adhere to damaged endothelium and undergo activation
- aggregation of platelets into a thrombus
what is in the cytoplasm of an activated platelet
- contractile proteins: actin and myosin and thrombosthenin
- residuals of both the endoplasmic reticulum and the Golgi apparatus that synthesis various enzymes and especially store large quantities of calcium ions
- mitochondria capable of forming ATP and ADP
- enzyme xystemsn that synthesise prostaglandins
- fibrin stabilising factor
- a growth factor that causes cell growth
what does the cell membrane of activated platelets contain
- 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 - phospholipids
- these are present in large amounts
- these activate multiple stages in the blood clotting process
what are the three stages of platelet plug formation
- adhesion and activation
- secretion and release
- aggregation
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
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
what is the protein found on cell membrane of platelets that adheres to the collagen
Glycoprotein Ib
what does glycoprotein Ib bind to
vWF
what also binds to vWF
glycoproteins IIb and IIIa adhere
what does the vWF act as
a bridge between platelet surface receptors and exposed collagen
how does glyocportein Ia bind to collagen
directly no vWF
Platelet adhesion diagram
what does prostaglandin synthesis activate
production of thromboxane A2
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
what is a blood clot composed of
- a meshwork of fibrin fibres ruling in all directions and entrapping blood cells
- platelets
- plasma
what are the two courses a clot can follow
- it can be invaded by fibroblasts which will subsequently form connective tissue through the clot
- it can dissolve
what breaks down a clot
- prostacyclin acts as an enzyme to dissolve the clot
2. the breakdown product of fibrinolysis - D dimer
what substances cause or affect blood coagulation in the blood and tissues
- procoagulant factors: promote coagulation
2, anticoagulant factors: inhibit coagulation
- co-factors: these aid blood coagulation
what does the blood coagulating depend on
the balance between the coagulate and anticoagulant factors
examples of a coagulation factors known by their description name :
- tissue factor - TF/FIII
2. prothrombin - FII
examples of coagulation factors known by their factor number:
- Factor VIIII (FVIII is associated with haemophilia A)
- Factor IX (FIX associated with haemophilia B)
where are most coagulation/anticoagulation/co-factors produced
the liver
2 substances that play a minor role in blood coagulation
- high molecular weight kiniogen (HMWK)
- prekallikrein
what are these substances active to
kininogen and kvllikrein
general mechanism of blood coagulation
- prothrombin activator is formed from the extrinsic/intrinsic pathway
- prothrombin activator, in the presence of Ca2+ converts prothrombin to thrombin
- thrombin causes polymerisation of fibrinogen molecules into fibrin fibres
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
what is required by the liver for normal formation of prothrombin
Vitamin K
steps of the extrinsic pathway
- traumatised tissue released tissue factor TF - a complex of phospholipids and a lipoprotein
- TF activates FVII into FVIIa
- TF and FVIIa together under the influence of Ca2+ ions activate FX to form FXa
- FXa combines with phospholipids and FV under the influence of Ca2+ to form prothrombin activator
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
what is the final prothrombin activator complex:
- FXa and FV
what causes the splitting of prothrombin to form thrombin
FXa
what does FV do
greatly accelerates the splitting of prothrombin
extrinsic pathway diagram
Step 1 of the intrinsic pathway
trauma to the blood alters two important clotting factors in the blood
what are the two clotting factors In blood in intrinsic pathway
XII and the platelets
what happens when XII is disturbed
forms XIIa
what lipoprotein does platelet phosopholid contain
platelet factor 3
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
step 3 of intrinsic pathway
XIa then activates Factor IX to IXa under influence of Ca2+
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
step 5 of intrinsic pathway
Xa combines with V and phospholipids to form prothrombin activator under the influence of Ca2+
intrinsic pathway diagram
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
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
diagram of whole coagulation cascade
