5. Atherosclerosis Flashcards
(96 cards)
1
Q
Thrombosis
A
• > Is a solidification of blood contents that forms within the vascular system.
due to haemodynamic disturbances
2
Q
What is virchow’s triad
A
3 factors for thrombosis – need 1 or 2 for thrombosis
3
Q
3 factors in virchow’s triad
A
• changes in the intimal surface (tunica intima in contact with lumen and blood) of the vessel
○ Injury to endothelium cells exposing sub endothelial surface (tunica intima in contact with lumen and blood)
• changes in the pattern of blood flow
○ Normal, sluggish, turbulent
• changes in the blood constituents
○ e.g. coagulation factors.
4
Q
5 injury events
A
○ Exposing VWD- von willebrand factor
○ Small mass of platlet of accumulation
○ Platlet mass is washed away by blood flow when normal
○ Tubulent blood flow or slugish blood flow – growth of small mass to larger mass
○ Mass can partially occlude lumen
5
Q
3 factors leading to endothelieum injury
A
- Hypertension
- Smoking
- Atherosclerosis – atherosclerosis plaque in intima
6
Q
3 factors in thrombus formation
A
- Endothelial injury
- Abnormal blood flow
- Hypercoagulability
7
Q
Arterial thrombosis
A
– endothelial injury, abnormal blood flow
* Atherosclerotic plaque * Lines of Zahn white layer (platlet) red layer (RBC)
8
Q
Venous thrombosis
A
– hypercoagulability, stasis
* Underlying cause due to immobility, muscle contraction * Hypercoagulability, stasis, sluggish blood flow * Gelatinous red mass due to less platlets
9
Q
Arterial thrombus formation
A
- Atheroma, with turbulence lipid filled cells
- Ulceration , loss of endothelial cells and exposure of collagen
- Platlet adherence , and activation
- Thrombosis, thrombus formed of alternating layers of platlets, fibrin and red cells
10
Q
appearance of arterial thrombi
A
- Pale – due to platlets
- Lines of Zahn
- Lower cell content than venous (venous has high rbc due to stasis)
11
Q
Appearance of thrombi
A
- Soft
- Red
- Gelatinous
- Higher cell content
12
Q
Outcome of thrombosis
5 outcomes
A
• Depends of size and site
- Lysis
- Propagation
- Organisation
- Recanalization
- Embolization
13
Q
Lysis
A
- Eat the small thrombus
- When the thrombus is relatively small
- • Dependent upon fibrinolytic activity (e.g. plasmin).
14
Q
Propagation
A
• Progressive spread of thrombosis
15
Q
Organisation
A
Ingrowth of fibroblasts and capillaries (similar to granulation tissue)
• lumen remains obstructed – blood cannot pass
16
Q
Recanalization / canalization
A
–> restore blood flow, even partially with small blood vessels, angiogenesis
Occurs by the ingrowth of new vessels
• The new vessels join up to restore blood flow, at least partially.
17
Q
Embolization
A
Caused by fragmentation of the thrombus
• Results in infarction at a distant site
Large thrombus passes through valve of vein
Causing fragmentation
Mass is released and travels within the vein
18
Q
Thrombus - definition
A
Blood clot that forms in a vessel
19
Q
Embolism - definition
A
Clot that travels from site where it was formed
20
Q
Thrombo - emboli
4 examples
A
- From atheromatous carotid arteries pass to the brain to cause stroke.
- From atheromatous abdominal aorta pass to arteries of the legs
• from systemic veins: pass to the lungs to form
Pulmonary emboli
• from the heart pass via the aorta to renal, mesenteric , and other curteries
21
Q
Effects of arterial thrombosis
A
- Ischaemia
- Infarction
- Depends on site and collateral circulation
22
Q
Effects of thrombosis on the heart
A
- artheromatous plaque with thrombos Atrial thrombus Valve vegetation Thrombus – old myocardial infarction Thrombus- recent myocardial infarct
23
Q
4 general effects of thrombosis - arterial
A
Cerebral infarct
Renal infarct
Ischaemic bowel
Ischaemic foot gangrene - dry
24
Q
Effects of venous thrombosis
A
–> stasis, blood is accumulated due to obstruction
- Congestion = causing accumulation of blood
- Oedema
- Skin ulceration
25
What is an embolus
---> An embolus is a mass of material in the vascular system able to become lodged within a vessel and block its lumen. - obstruction
* Most emboli originate from thrombi Embolism
* The most common type is pulmonary embolism from lower limb deep vein thrombosis
26
Deep vein thrombosis - predisposing factors
```
---> anything increasing coagulation factors in the blood – contributing to stasis and sluggish blood flow
• Immobility/bed rest
• Post-operative
• Pregnancy and postpartum
• Oral contraceptives
• Severe burns
• Cardiac failure
• Cancer
```
27
Deep vein thrombosis
* Swelling
* Redness
* Damage small vessel in lung
Can cause Effect of pulmonary embolism
• Depends on the size of the mass
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Pulmonary embolism (pe)
Embolus derived from a lower-extremity deep venous thrombus lodged in a pulmonary artery branch.
- embolus from deep vein thrombosis travels in circulation to pulmonary arteries
• Disruption can affect bifurcation
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Massive PE
>60% reduction in blood flow: rapidly fatal
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Major pe
medium sized vessels blocked. Patients feel chest pain with shortness of breath +/-cough and blood- stained sputum.
• Corpalmanal, can lead to right side heart failure
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Minor pe
-small peripheral pulmonary arteries blocked. Asymptomatic or minimal shortness of breath
• Recurrent minor PEs lead to pulmonary hypertension – that can also lead to right sided heart failure
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Pulmonary embolism
| Symptoms
* Chest pain
* Shortness of breath
* Haemostasis
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Saddle embolism
* Embolus disrupts bifurcation of main artery in pulmonary circulation
* Critical condition
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5 Other types of embolism
* Paradoxical emboli
* Emboli from atheroma
* Fat and bone marrow emboli
* Amniotic fluid
* Gas embolism
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7 types of embolism
* Paradoxical emboli
* Emboli from atheroma
* Fat and bone marrow emboli
* Amniotic fluid
* Gas embolism
* pulmonary embolism
* saddle embolism
36
Paradoxiacal emboli
• Originate in venous system but damage occurs in arterial system
• Because
○ Embolus is very small so it passess through and is pumped to other organs
○ Embolus is large but is in the right atrium, due to defect it can pass to left atrium (due to atrial septal defect) so mass moves from right atrium to left atrium down pressure gradient through spetum defect
37
Atheroma
* Vulnerable plaque, large lipid core, thin fibrous cap
| * Atheroma fragments and ends up in the lumen act as a source of occlusion
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Fat and bone marrow emboli
* Fat droplet
* See bone marrow componets too
* Boen marrow and fat components travel through blood circulation and form a mass
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Fat and bone marrow emboli
| When does it happen
* Fracture
* Trauma
* Following surgery like liposuction
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Air or gas embolism
---> happens in divers because they move fom high to low pressure areas
Dissolved gas release on surface as bubbles
Bnitrogen bubbles travel within the vessel and cause damage
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Air or gas embolism
Symptoms
* Joint pain
| * Resparitory pain
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Thromboembolic disease
Treatment
* Aspirin – antithrombogenic drug, prevent thrombaxin (coagulation factor) a2 formation
* Heparin
* Warfarin
* Filters – e.g. stents in the heart, IVC
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Thromboembolic disease
Prevention
Encourage light exercise to prevent stasis
Leg elevation – blood back to heart
Avoid risk factors
e.g. avoid risk factors for atherosclerosis
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5 Essentials of haemostasis
* Keep blood moving – heart, venous valves function
* Blood vessels
* Platelets
* Coagulation factors
* Anticoagulant factors
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Action of platlets
1. Clot initiation
• Vessel wall is breached
• Platelets flock to that place and become aggregated
• Activate coagulant factors
• Coagulation – releases and produced thrombin
2. Clot formation
• Thrombin activates fibrinogen (inactive plasma protein) into fibrin
• Fibrin polymers form
3. Fibrinoiyosis
• Clot retracts and breaks up
• Mediated by plasminogen pathway
46
Platelet plug
1. Vessel contracts – not enough to stop bleeding
2. Exposure of vessel wall attracts platlets
• Platelets are at the wall sticking to injured vessel and connective tissue – platlet plug
Platelet plug - can initially control bleeding, form quickly
• Alone it is not satisfactory
47
Secondary haemostatic blood clot
After platelet plug
| • Fibring filaments stabilise plug into blood clot
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Platelets
---> Megakaryocytes produce platelets in the bone marrow, platlets are fragments of megakaryocytes
* Platelets ‘bud’ from cytoplasm
* Normal platelet count is 150-400 x 109/L
* Normal life span 7-10 days
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3 roles of platelets
Platelet adhesion
Platelet activation
Platelet aggregation
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Platlet adhesion
1. Damage to vessel wall
2. Exposure of underlying tissues
3. Platelets adhere to collagen via vWF/receptor( vonwilibrand)
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Platlet activation
Activation by
• Collagen in vessel wall
• ADP released by damaged cells
• Thromboxane A2 – powerful platlet aggregator released by activated platlets
• Thrombin from clotting cascade is activated and activates platlets
When platelets are activated
• Platelets stick to subendothelieum on vonwilibrand factor
• Vonwilibrand factor is large – can grab lots of platlets
52
Aspirin
* Inhibits cyclo oxygenase – responsible for thromboxane a2
| * That is why aspirin reduces platelet aggregation
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Platelet aggregation
---> cross linking of platelets to form a platelet plug
54
Mediating factors in clotting
* Plt(platelet) receptors – glycoprotein complexes e.g. GP1b-V-IX, GPIIb-IIIa
* Von willebrands factor
* Fibrinogen
* Collagen
* ADP
* Thromboxane/arachidonic acid Thrombin
55
Clotting cascade
1. Amplification system activation of precursor proteins to generate thrombin (IIa)
2. Thrombin converts soluble fibrinogen into insoluble fibrin
3. Insoluble fibrin Enmeshes initial platelet plug to make stable clot
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Control of clotting cascade
◦ Natural anticoagulants to inhibit activation
◦ Clot destroying proteins which are activated by the clotting cascade
(both are carefully balanced!)
• So thrombus formation doesn't occur or this doesn't go unchecked
57
Thrombophilia
• Clot destroying proteins are inadequate not working etc
58
Coagulation factors
Made in liver
```
– most are pro enzymes (activate next enzyme)
Fibrinogen (1)
• Prothrombin (2)
• Factor 5
• Factor 7
• Factor 8
• Factor 9
• Factor 10
• Factor 11
• (factor 12)
• Factor 13
• Tissue factor
```
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Natural anticoagulants
* Protein C
* Protein S
* Antithrombin
* Tissue factor pathway inhibitor
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Vitamin K
Factors 2,7,9,10 and protein C and S = require vitamin K for thei synthesis
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2 clotting cascade pathway
Intrinsic pathway
| Extrinsic pathway
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• Intrinsic pathway
○ Factors used are contained within the blood
○ Triggered by negative surface
○ No blood vessel is needed to be broken open for it to occur
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• Extrinsic pathway
○ Factors used are present outside of the blood
| ○ Triggered by thromboplastin released from damaged cells adjacent to area of hemorrhage
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What things are essential for clotting to occur
Factors 9,8,7, 10 and 5, thrombin and fibrinogen are essential for clotting to occur
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2 tests to measure coagulation
Prothrombin time
| Aptt
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Extrinsic pathway – prothrombin time
* If extrinsic pathway is abnormal prothrombin and thrombin time are prolonged
* Factor 7
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Intrinsic pathway – APTT
* Something wrong with intrinsic pathway APTT would be prolonged
* Factors 8,9,11,12
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Measurement for common pathway
* Factors 5, 10, prothrombin and fibrinogen
| * Expect prolonged prothrombin APTT and fibrinogen
69
Haemophilia a
* Deficenisy of factor 8 in intrinisc pathway
* Prolonged APTT
* But factor 7 can also be used so APTT may be less prolonged
◦ X-linked recessive
◦ due to Congenital lack of factor VIII
◦ Mild/moderate/severe depending on amount of factor VIII present
◦ Diagnosed pre-natally or soon after birth if family history, or usually in infancy if new spontaneous mutation
◦ Bleeding into muscles and joints, and post- operatively
◦ Treated with recombinant factor VIII or DDAVP (Desmopressin)
70
Haemophiliacs a and b
• Have prolonged APTT
| but normal prothrombin and thrombin time
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Laboratory tests
* Prothrombin time (PT) – measures extrinsic and common pathway (F VII, V, X, protombin and fibrinogen). INR is derived/calculated from this and is used the measuring warfarin.
* Activated partial thromboplastin time (APTT) – measures intrinsic and common pathway (F VIII, IX, XI, XII, V, X, prothrombin and fibrinogen)
* Fibrinogen count measures the amount of fibrinogen
72
Von wilibreand factor
---> Involved in platelet adhesion to the vessel wall, platelet aggregation, and also carries Factor VIII
• Involved in primary haemostatic plug and secondary haemostatic plug
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Vonwillebrand disease
* Deficient vonwillebrand factor
* When disease is severe – mucousal bleeding, big joint bleeding
* Most common inherited bleeding disorder
* Majority are asymptomatic due to compensations
* Abnormal bleeding time and APTT as it affects both factor 8 and platlets
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Vessel wall
Vasoconstriction
• Contracts and trap platelets
Endothelieum
• Balances oposing and favouring clotting
• Secreting substance – tissue plasminogen activation and thrombomodulin (activates protein C)
Production of Von Willebrands factor (vWF)
◦ Essential for plt adhesion
◦ Carrier and ‘protector’ of Factor 8 (clotting protein)
Exposure of collagen and Tissue factor which initiates activation of clotting factors (proteins)
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Factors that opose clotting
* Natural anticoagulants – oppose foramtion of firbin – antithrmobin, protein C, proteinS
* Diluting of coagluative factors
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Anticoagulants
---> blood clot is lysed
1. Trigger
2. Anticoagulants produce thrombin
3. Fibrin net and blood clot
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3 natural anticoagulants
◦ Protein C
◦ Protein S
◦ Anti-Thrombin
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Coagulation cascade
• Eventually produce thrombrin to make fibrin
• Antithrombin – regulates and inhibits thrombrin
Protein s and C are activated to inhibited factors5 and 10
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Plasminogen
* Pathways to break dwon fibrin clot
* Inactivated form of plasmin
* Plasmin breaks down clot
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Fibrinolysis
Once clots have been made
* Breakdown of clot
* Plasminogen activate activates plasminogen to plasmin
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D Dimers
• D Dimers – measures fibrin degradation products
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Clinical relevance of haemostasis
* Bleeding disorders
* Arterial thrombotic disorders
* Venous thrombotic disorders
Abnormal blood test results
Drug therapy for pro- or anti-thrombotic purposes
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Bleeding disorders
Due to abnormality in the vessel wall, platelets or coagulation factors
Inherited and acquired
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Congenital Coagulation factor disorders
* Haemophilia A (Factor 8)
| * Haemophilia B (Factor 9) etc
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Acquired Coagulation factor disorders
* Liver disease
* Vit K deficiency (F II, VII, IX, X)
* Anticoagulants including Warfarin (inhibits Vit K)
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Coagulation factor disorders
* Muscle haematomas
* Recurrent haemarthroses
* Joint pain and deformity
* Prolonged bleeding post dental extraction
* Life threatening post op and post traumatic bleeding
* Intracerebral haemorrhage
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Haemophilia B
Similar presentation to haemophilia A
◦ Congenital reduction in factor IX
X linked recessive
Similar to haemophilia a just much more rare
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Von willebrand's disease
Cause
* Several genetic defects cause this condition
* Main type due to a reduction in vWF production.ie not enough
* (others where activity reduced)
* Present with post-partum hemorrhage, prolonged APTT, heavy period bleeding
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Examples of vWD bleeding
```
Platelet associated bleeding
Skin and mucous membrane bleeding
• epistaxis
• gum bleeding
• bruising
```
Prolonged bleeding after trauma
• Heavy periods
• Post surgery
• Post dental extraction
Spontaneous joint or muscle bleeding is rare but can be seen in tupe 3 vWD
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Vessel wall abnormalities
Easy bruising – in more elderly patients, those with scurvy or taking aspirin
Spontaneous bleeding from small vessels
Skin mainly
Can be mucous membranes
Hereditary hemorrhagic tenetplasia – small blood vessels popping and bleeding
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Congenital Problems with vessels
• Hereditary Haemorrhagic Telangiectasia (HHT)
◦ Autosomal dominant
◦ Dilated microvascular swellings increase with time
◦ GI haemorrhage can lead to iron deficiency anaemia
difficult to diagnose can use colonoscopy
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Accquired problems with vessels
* Senile purpura
* Steroids
* Infection eg measles, meningococcal infection
* Scurvy-Vit C def causing defective collagen production
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Disseminated intravascular coagulopathy (DIC)
Type of microangiopathic haemolytic anaemia
--> secondary complication of another disorder e.g. sepsis, trauma, burns, childbirth complications (amniotic fluid embolism)
1. Pathological activation of coagulation
2. Numerous microthrombi are formed in the circulation
3. But also broken down products of coagulation, not broken down properly, left as D dimers – found everywhere in blood forming microthrombi
* This leads to consumption of clotting factors and platelets, and a haemolytic anaemia
* Clotting tests are affected - usually raised PT/INR, raised APTT, low fibrinogen (as it is used up) and raised D dimers/fibrin degradation products, high LDH lactate dehydrogenase due to torn RBC
* Patient may experience haemorrhage as fibrin plug not formed properly
* Risk of bleeding and thrombosis
* Symptoms, gangrene of skin, renal failure, necrosis of fingers toes etc.
* Identify with blood film – red cells look completely broken up – indicate microangiopathy
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Disseminated intravascular coagulopathy (DIC)
| Treatment
* Want to try and stop process that initiated it as it can kill patient
* Treat bleeding with ffp – fresh plasma with clotting factors
* Treat the source e.g. If cause is bacteria sepssi give antibiotics
95
DIC – triggers
◦ Malignancy
◦ Massive tissue injury eg burns
◦ Infections – usually gram negative sepsis
◦ Massive haemorrhage and transfusion
◦ ABO transfusion reaction – mismatch between A B and O blodo tranfusion
◦ Obstetric causes – placental abruption, pre-eclampsia, amniotic fluid embolism
96
Thrombophilia's
--> These are acquired or congenital defects of haemostasis which can increase a patient’s risk of thrombosis
Deep vein thrombosis or pulmonary embolism
* Congenital causes include deficiency in natural anticoagulants (protein C, protein S and antithrombin deficeinies - severe) and an abnormal factor V (factor V Leiden)
* Acquired causes include antiphospholipid syndrome – antibodies against platelet membrane
* Specialised tests can test for these conditions
* These are relatively rare conditions (protein C, protein S and antithrombin deficeinies - severe) and many patients with them do not develop clots unless they have additional risk factors
