Blood 5 Flashcards
Describe the main structural differences between arteries and veins
Arteries:
- Thick tunica external made of collagen
- Thick tunica intima
- Narrow lumen
- High pressure and fast blood flow
- No valves
Veins:
- Thin tunica external made of collagen
- Thin tunica intima
- Wide lumen
- Low pressure and slow blood flow
- Valves present to prevent back flow
Classify common conditions using the following causes: venous and arteriole thrombosis.
Arteriole:
- Myocardial Infarction
- Stroke
- Atrial Fibrillation
- Peripheral Vascular Disease - a disease that causes restricted blood flow to the arms, legs, or other body parts (can occur in arteries and veins)
Venous:
- Deep vein thrombosis (DVT)
This can lead to a pulmonary embolism
Discuss how deep vein thrombosis occurs
- There is a low pressure in the veins. This can cause the red blood cells to accumulate in the veins - this especially occurs around the valves.
- This causes an inflammatory response in the cells in the endothelium.
- This can activate platelets, but the primary result is to cause the cells start expressing tissue factor.
- The tissue factor then combines with activates Factor VII. This can then activates Factor X, stimulating the common coagulation Pathway.
- The Tissue factor therefore stimulates the coagulation cascade. This results in the production of fibrin. ]
- A clot is therefore established and made up of primarily fibrin and red blood cells (it has few platelets).
Discuss how pulmonary embolism develops.
What is are the symptoms and treatment?
The thrombus in the leg becomes unstable. As a result, an embolism breaks off and travels through the blood stream to be lodged in the pulmonary artery. This blockage can be life-threatening.
Symptoms: shortness of breath, fever, sweating, chest pain and coughing up blood.
Treatment: Immediately use unsaturated Heparin. Heparin increases the activity of antithrombin. Later, Warfarin can be used.
What can result from DVT?
Oedema. The clot put pressure on the blood vessel. This causes endothelial cells to become leaky. Fluid therefore escapes the blood vessel and accumulates in the interstitial space. This causes swelling. If you press on the leg, the indentation remains.
What are the main risk factors for venous thrombosis?
- Immobilisation
- Cancer
- Pregnancy
- Oral contraceptives
- Genetic risks e.g. Factor V Leiden. This is a genetic defect in Factor V. Factor V - in contrast to other factors, is not an enzyme - functions as a cofactor. Factor Va combines with Factor Xa to produce thrombin. In Factor V Leiden, Factor Va is resistant to inactivation. As a result, it remains switched on, and so leads to the increase in thrombin. This means individuals with Factor V Leiden have a higher chance of developing DVT.
How do endogenous anticoagulants work? Give examples.
Endogenous anti-coagulants include AT - Anti-thrombin. Anti-thrombin moves throughout the body, neutralising thrombin molecules that are activated away from a site of injury. Anti-thrombin is a serpin.
Another endogenous anti-coagulant are aPC and PS. These block part of the pathway involved in the production of thrombin.
How does fibrinolysis work? How can the product be used in the test for thrombosis?
The enzyme tissue plasminogen activator (tPA) converts Plasminogen to Plasmin. Plasmin is a serpin. Plasmin can then break down fibrin. The product of the break down of fibrin is D-Dimers. These D-Dimers are not usually present in the blood and so there detection could mean there is active thrombosis. A high level of D-Dimers can indicate a large clot such as those in DVT.
How do arterial thrombi develop?
- Atherosclerosis - Overtime LDL is deposited into the blood vessel forming a plaque. This can accumulate and block the blood vessel. The lipids become oxidised causing the endothelial cells to become cytotoxic, leading to inflammation. This leads to the infiltration of macrophages. The plaque becomes necrotic.
- The thrombotic event is when the plaque ruptures, damaging the vessel wall.
- This causes platelet adhesion and activation.
- As a result a platelet rich clot is formed.
- Since the lumen of the blood vessel is narrower, it is likely to result in the occlusion of the blood vessel.
What are the main risk factors for arterial thrombosis?
- Advanced age
- Lack of exercise
- Diabetes
- High cholesterol
- Hypertension
- Smoking
- Ethnicity
- Poor diet
What is Virchow’s triad?
Virchow’s triad describes the three broad categories of factors that are thought to contribute to thrombosis:
- Stasis
- Hyper-coagulability
- Vessel Wall injury
What are the two types of arteriole thrombosis? What are the differences?
Mural thrombosis:
- The clot is unstable
- It does not occlude the blood vessel
- Causes unstable angina and TIAs
Occlusive thrombosis:
- Stable, robust clot that blocks the blood vessel
- Cause of myocardial infarction and cerebral infarction (an area of necrotic tissue in the brain)
What are the stimulatory agonists secreted by platelets?
- ADP
- Thromboxane A2
- Thrombin
- Fibrinogen
- Serotonin
- ATP
- Von Willebrand Factor
- Adrenaline
What are the inhibitor agonists secreted by platelets?
- Adenosine
- Prostacyclin
- Nitric Oxide
What are pathological ligands in the context of coagulation?
Ligands found in the blood - that are not normally present - after thrombosis. These include chemokines and oxidised lipids. Changes in the balance of these ligands lead to pathological hemastasis.
