Homeostatis & thrombosis Flashcards
What is blood pressure?
- Systolic Pressure: During contraction of the left ventricle (systole).
- Diastolic Pressure: During relaxation of the ventricles (diastole).
Formula: Blood Pressure = Cardiac Output x Peripheral Resistance.
- Diastolic Pressure: During relaxation of the ventricles (diastole).
How to measure blood pressure?
- Use a calibrated sphygmomanometer.
- Ensure patient is relaxed, seated, and arm supported at heart level.
- Measure in both arms initially to check for discrepancies.
What is the aetiology of hypertension?
- Primary (Essential) Hypertension: >95% of cases, idiopathic.
- Secondary Hypertension:
○ Renal/Renovascular Disease
○ Endocrine Disorders:
§ Phaeochromocytoma
§ Cushing’s Syndrome
§ Conn’s Syndrome
§ Acromegaly, Hypothyroidism
○ Coarctation of the Aorta
○ Pregnancy-related Hypertension
○ Medications: Hormonal contraceptives, steroids.
- Secondary Hypertension:
What is the role of RAAS in blood pressure?
- Renin-Angiotensin-Aldosterone System (RAAS): Regulates blood pressure and fluid balance.
- Mechanism:
○ Renin release ➔ Angiotensin I ➔ Angiotensin II (vasoconstrictor) ➔ Aldosterone release ➔ Sodium and water retention.
- Mechanism:
How is blood pressure diagnosed?
- Initial Measurement: Clinic BP ≥140/90 mmHg.
- Confirmation:
○ ABPM (Ambulatory Blood Pressure Monitoring) or
○ HBPM (Home Blood Pressure Monitoring). - Severe Hypertension: Immediate treatment if BP ≥180/110 mmHg.
- Confirmation:
What are the NICE guidelines of hypertension staging?
Stage 1: Clinic BP ≥140/90 mmHg; ABPM/HBPM ≥135/85 mmHg.
Stage 2: Clinic BP ≥160/100 mmHg; ABPM/HBPM ≥150/95 mmHg.
Severe Hypertension: Clinic BP ≥180/110 mmHg.
What is the management of hypertension?
Lifestyle Modifications:
○ Healthy diet, reduce salt and alcohol intake.
○ Encourage exercise and weight loss.
○ Smoking cessation.
Pharmacological Treatment: As per patient profile and BP stage.
What are the common presentations of clotting disorders?
- Petechiae, purpura, ecchymosis, hematomas.
- Bleeding from nose, gums, gastrointestinal, and genitourinary tracts.
- Joint/muscle bleeding, excessive post-surgical bleeding.
What are some of the hereditary clotting/coagulation disorders?
-Haemophilia A: Factor VIII deficiency.
-Haemophilia B: Factor IX deficiency.
Von Willebrand’s Disease
What are the acquired clotting/coagulation disorders?
-Vitamin K deficiency.
-Liver disease.
- Disseminated Intravascular Coagulation (DIC).
-Anticoagulant therapy.
What is thrombosis and what are the different types?
Formation of blood clots that block blood supply.
Types:
-Arterial Thrombosis ➔ Affects arteries. (strokes and heart attacks)
-Venous Thrombosis ➔ Affects veins. (pulmonary embolism and deep vein thrombosis)
What is haemostasis?
The process of stopping bleeding and repairing damaged blood vessels.
Summary of Major Steps:
1. Vasoconstriction (reduce blood flow)
2. Platelet plug formation (adhesion, activation, aggregation)
3. Coagulation cascade (fibrin clot formation)
4. Clot stabilization (via Factor XIII cross-linking)
5. Fibrinolysis (clot breakdown)
Explain the steps of primary haemostasis.
Primary Haemostasis (Formation of the Platelet Plug)
This is the initial, rapid response to vascular injury and involves platelets.
- Vasoconstriction:
Immediately after injury, the blood vessel constricts to reduce blood flow.
This is mediated by endothelin released from endothelial cells and neural reflexes. - Platelet Adhesion:
The injury exposes subendothelial collagen and von Willebrand factor (vWF), which helps platelets stick to the site of injury.
Platelets bind to vWF via Glycoprotein Ib (GPIb) receptors on their surface. - Platelet Activation:
Once adhered, platelets change shape from disc-like to spiky, increasing their surface area.
They release chemical signals from granules, such as ADP, thromboxane A2 (TXA2), and calcium, which further recruit and activate more platelets. - Platelet Aggregation:
Activated platelets express Glycoprotein IIb/IIIa (GPIIb/IIIa) receptors, which bind fibrinogen.
Fibrinogen links platelets together, forming a primary platelet plug.
Explain the steps of secondary Haemostasis.
Secondary Haemostasis (Stabilization of the Platelet Plug via the Coagulation Cascade)
This step reinforces the platelet plug by forming a fibrin mesh.
- Activation of the Coagulation Cascade:
The cascade involves two pathways:
Intrinsic pathway: Triggered by exposure to collagen and involves Factors XII, XI, IX, and VIII.
Extrinsic pathway: Triggered by tissue factor (TF) released from damaged tissues and involves Factor VII.
Both pathways converge at the common pathway with Factor X. - Thrombin Generation:
Factor Xa converts prothrombin (Factor II) into thrombin.
Thrombin is crucial as it:
Converts fibrinogen into fibrin strands.
Activates Factor XIII, which cross-links fibrin, stabilizing the clot.
Further activates platelets and enhances the coagulation cascade (positive feedback). - Formation of the Fibrin Clot:
The fibrin mesh integrates with the platelet plug, creating a stable, solid clot.
Explain the steps of fibrinolysis.
Fibrinolysis (Clot Breakdown)
Once the vessel is healed, the clot is no longer needed and is broken down.
- Activation of Plasminogen:
Tissue plasminogen activator (tPA) converts plasminogen (inactive form) into plasmin. - Fibrin Degradation:
Plasmin digests fibrin into fibrin degradation products (FDPs), including D-dimers.
This dissolves the clot, restoring normal blood flow.
How is haemostasis regulated?
The body uses natural anticoagulants to prevent excessive clotting:
Antithrombin III: Inhibits thrombin and Factor Xa.
Protein C and Protein S: Inactivate Factors Va and VIIIa.
Tissue Factor Pathway Inhibitor (TFPI): Regulates the extrinsic pathway.
What is the difference between the extrinsic vs intrinsic pathway?
Key Differences:
Initiation:
The intrinsic pathway is activated by damage to the blood vessel itself (or artificial surfaces).
The extrinsic pathway is activated by tissue damage that exposes tissue factor.
Complexity:
The intrinsic pathway involves more clotting factors and steps.
The extrinsic pathway is simpler and faster, involving fewer factors.
Speed:
The extrinsic pathway is the initial, rapid response.
The intrinsic pathway acts as a secondary amplification mechanism.
What is the extrinsic pathway?
Extrinsic Pathway (Tissue Factor Pathway)
Trigger: The extrinsic pathway is initiated by trauma to the blood vessel, which exposes the tissue factor (TF) on the subendothelial cells.
Key Factors: It involves Factor VII and Tissue Factor (TF), which is a protein found on the surface of damaged cells.
Cascade Steps:
Tissue Factor (TF), exposed on the damaged tissue, binds with Factor VII to form a complex (TF-VIIa).
The TF-VIIa complex activates Factor X to Xa.
Overall Role: This pathway is much faster because it requires fewer steps. It provides a rapid initial response to injury.
What is the intrinsic pathway?
Intrinsic Pathway (Contact Activation Pathway)
Trigger: The intrinsic pathway is triggered when blood comes into contact with damaged vessel walls or foreign surfaces (like glass or collagen).
Key Factors: It involves clotting factors XII, XI, IX, and VIII (along with calcium ions). Factor XII is activated when it comes into contact with negatively charged surfaces, starting the cascade.
Cascade Steps:
Factor XII gets activated to XIIa.
Factor XIIa activates Factor XI to XIa.
Factor XIa activates Factor IX to IXa.
Factor IXa, with the help of Factor VIIIa, activates Factor X to Xa.
Overall Role: This pathway is slower because it involves a series of enzymatic activations, but it amplifies the clotting response.
What is the final common pathway?
Both pathways eventually converge at the activation of Factor X to Xa, which is essential for converting prothrombin to thrombin, leading to clot formation.
Summary of the Final Common Pathway:
Factor X is activated (via intrinsic or extrinsic pathways).
Factor Xa forms the prothrombinase complex with Factor Va and converts prothrombin to thrombin.
Thrombin converts fibrinogen to fibrin, creating the clot, and activates Factor XIII to stabilize the fibrin mesh.
What are the different coagulation tests?
- APTT (Activated Partial Thromboplastin Time): Measures intrinsic pathway.
Factors: XII, XI, IX, VIII, X, V, II, I.
Prolonged aPTT may indicate deficiencies in intrinsic pathway or can be caused by use of heparin( anticoagulant). Its also used to monitor heparin therapy. - PT (Prothrombin Time): Measures the time it takes for blood to clot thus measures extrinsic pathway.
Factors: VII, X, V, II, I.
Prolonged PT may indicate deficiencies in clotting factors (especially Factor VII) or liver dysfunction, or may be influenced by anticoagulant therapy (e.g., warfarin). - INR (International Normalized Ratio): Standardized PT measurement.
What are the indications of INR values in time of therapeutic range (TTR)?
- INR <1.7: Increased risk of thromboembolism.
- INR >4.0: Increased risk of bleeding.
What is Warfarin?
It is an oral anticoagulant used to prevent and treat blood clots e.g DVT and PE.
What are the main challenges of Warfarin?
Excessive bleeding which can be life threatening. signs include easy bruising, nosebleeds, blood in urine or stools, prolonged menstrual bleeding etc.
There are dietary interactions as its effectiveness can be influences by foods high in vitamin K.
- Poor TTR, drug and food interactions, frequent INR monitoring.
Impact: Can significantly affect patient quality of life.
Warfarin can be reversed by vitamin K administration or fresh frozen plasma.
