Blood Pressure & Haemostasis
Role of arteries
Low resistance conduit to conduct blood fast. They have elastic walls to expand when the heart contracts. They expand to accommodate full SV and absorb energy from the blood. Some of the blood is retained and does not pass into the arterioles as the arterioles offer resistance. During diastole the arteries recoil and push more blood to the capillary beds via the arterioles as the potential energy stored during systole is converted to kinetic energy which drives the blood forward. This is the windkessel effect. This dampens the pulse I.e. It does not drop down to nearly 0mmHg of pressure during diastole but remains at 80mmHg.
Normal systolic pressure is created by stroke volume as blood is forced into the arteries. Diastolic pressure is created by the recoil of the elastic walls. High resistance arterioles make the artery diastolic pressure high as they do not let all the blood through so cause the arteries to retain blood. Higher resistance means more blood retained therefore a greater windkessel effect.
Older artery walls (sclerosis, fatty plaques) are stiffer so have a reduced ability to absorb blood pressure during systole therefore lower diastolic pressure. The heart must therefore produce higher systolic blood pressure to maintain adequate diastolic run off.
Mean blood pressure is diastolic pressure plus one third of the pulse pressure, pulse pressure is systolic minus diastolic blood pressure. Diastolic pressure comes in twice as heart spends much more time (75%) in diastole than systole.
Arteries are highly innervated by the sympathetic nervous system. Control is similar to starlings law (intrinsic mechanism, if they are stretched they will recoil more) and extrinsic is sympathetic nerve actively causing constriction (alpha one receptor). Resistance is proportional to one over the radius to the power of four so if you half the radius resistance increases 16 fold More resistance in arterioles means more blood retained in arteries so higher blood pressure but less blood flow to capillaries.
Changes in position
- Blood pressure changes when you move from lying to standing as 500mls of blood needs to be transferred from the intrathoracic vesses to the vessels in the lower limb
- This takes around 15seconds
- BP can fall by 20mmHg
- Reflex action by the baroreceptors: tachycardia, inotropic effects, vasoconstriction, increased TPR.
- Increased CO2
- Redictribution of blood to maintain head and heart
- Increase systolic BP
- Decrease peripheral resistance due to metabolites
- Increase in ventricle resistance stretching the atria allowing it to pump more, important in tachycardia when filling time is decreased
- Increased ventricular suction sue to increased parasympathetic supply
- Nor/adrenaline provide increased contractility
- Vagal withdrawal induces tachycardia
- Venous return is increased
- essential-No known cause
- secondary hypertension
- Renal artery stenosis
- ↓angiotensin II
- ↑bradykinin (vasodilation ↓TRP)
Angiotensin II antagonists
- Inhibition of angiontensin II and therefore causeing vasodilation
- Nifedipine- vascular tone. Verapamil- cardioselective
- Causes vasodilation ↓TPR and venous pressure
- ↓LDL, VLDL, TGA ↑HDL therefore reduces the chance of coronary artery
- Interacts with inositol triphosphate in vascular smooth muscle ↓TPR and BP
- Activates smooth muscle ATP sensitive K+ channels causing hyperpolarisation and hence vasodilation
- Decomposes in to NO ↑ cGMP- vasodilation
Fit, healthy young people can lose approximately 30% of their blood volume before blood pressure control mechanisms cannot keep BP at a normal value. Shock then occurs- acute failure of the CVS to supply nutritional blood flow to all tissues
- HYPOVOLAEMIC: blood loss
- SEPTIC: bacterial toxins
- ANAPHYLATIC: due to excessive immunological/ allergic response
- CARDIOGENIC: due to mechanical or electrical failure of the heart
- Refractory shock occurs when the mechanisims used by the CVS are not good enough to restore BP this causes positive feedback and is irreversible.
- Decrease in blood pressure
- Pulse rapid and feeble
- Skin veins collapse
- Skin pale, cool and moist
This is also known as clotting.
- Vasoconstriction: exposure of basement collagen in blood vessels activates platelets, mediated by 5HT (serotonin) and TXA2. Increase in sympathetic innervation leads to swelling and spasming of vascular smooth muscle.
- Platelet plug: release of von Willebrand Factor, TXA2 and Platelet Activation Factor increases intracellular Calcium levels. This causes the 'stellate' appearance of platelets and the activation of glycoproteins on the platelet surface, encouraging the platelets to bind together and 'plug' the wound.
- Clotting: trauma to the endothelial cells leads to tissue factor release, activating the coagulation cascade.
This is a cascade of reactions that concludes in the creation of cross-linked fibrin clots.
- Extrinsic Pathway: Tissue factor activates Factor VII, which in turn activates Factor X. This cleaves Prothrombin (Factor II) to Thrombin.
- Intrinsic Pathway: Exposure to basement collagen activates Factor XII, which in turn activates Factor X, and acts as above.
- Thrombin Amplification: Production of thrombin activates Factor XI in the Intrinsic Pathway, thereby accelerating the production of thrombin. Thrombin also cleaves fibrinogen (Factor I) to fibrin through thrombin-activated Factor XIII.
- Common Pathway: Fibrin combines with the activated platelets to form a clot over the damaged endothelium.
This is the process by which fibrin clots are broken down, by inactivating certain clotting factors.
- Release of NO/Prostaglandin I2: these mediators oppose vasoconstriction by acting on vascular smooth muscle.
- Antithrombin: inactivates Factor X, preventing the cleavage of prothrombin to thrombin.
- Proteins C and S: these Vitamin K-dependent proteins combine with thrombomodulin to produce Activated Protein C, which inactivates Factors X and V.
- Plasmin: Thrombin itself stimulates release of urokinase and tissue plasminogen activator (tPA), which cleave plasminogen to plasmin. This protein breaks down fibrin.
Certain conditions create a state of disordered haemostasis, where clots are either formed too rapidly or not formed at all.
- Thromboses e.g. Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE). Contributed to by three main factors: hyper-coagulability, haemodynamic changes (e.g. stasis) and damage to the blood vessel endothelium. Treated with thrombolytics.
- Idiopathic Thrombocytopenia Purpura (ITP): Autoimmune condition causing a low platelet count. Treated with immunosuppresants.
- Haemophilia: X-linked genetic condition, made famous by the British Royal Family. Type A involves a deficiency in Factor VIII, whereas Type B involves a deficiency of Factor IX. Treated by factor supplementation.