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Blood vessels

Organisation of the Body

Question	Answer
Functions of vessels	Oxygen delivery CO2 removal Nutrient delivery Waste removal Delivery of hormones Regulate blood flow Specialised functions
Components of circulatory system	Heart Arteries Capillaries Venins Lymphatic system - collects lymph and delivers it back
Macrovasculature	Vessels > 0.1 mm in diameter Arteries Veins
Microvasculature	Vessels < 0.1 mm Arterioles Capillaries Venules
Pulmonary circuit	Carries blood to and from the lungs
Systemic circuit	Distributes blood to and from all organs and tissues of the body
Portal system	Blood carried from one site to another without directly involving the heart Hepatic portal system - gastrointestinal to liver Hypothalamic pituitary portal system - hypothalamus to anterior pituitary
Arteries	Thick walled vessels Transport blood away from the heart Branch into smaller and smaller vessels - arterioles Usually round in histological sections
Capillaries	Thin walled vessels Form capillary beds where substances passed between blood and tissues Usually collapsed
Veins	Drain capillary beds - venules From larger and larger vessels returning blood to heart Also have valves
Components of vessel walls	Endothelium Muscular tissue Elastic tissue Connective tissue
Tunics	Layers of vessel walls Tunica intime - endothelium Tunica media - muscle or elastic Tunica adventitia - connective tissue
Tunica intima	Innermost layer Composed if a single layer of flattened squamous epithelial cells and basal lamina Sub endothelial tissue Internal elastic lamina Acts as a principle barrier to plasma from exiting lumen
Tunica media	Composed mostly of smooth muscle cells orientated concentrically around the lumen replaced by elastic in elastic arteries External elastic lamina
Tunica adventitia	Outermost layer composed mainly of fibroelastic connective tissue arranged longitudinally with adipose tissue
Internal elastic lamina	A thin band of elastic fibres in tunica intima Well developed in medium sized arteries With fenestrations that allow substances to diffuse between lumen and deeper regions of arterial walls to nourish these cells
External elastic lamina	Another band of elastic fibres in outermost layer of tunica media Not distinguishable in all arteries
Endothelium	Smooth surface - orientated along line of flow Regulates clotting and vascular tone and flow Secretes collagen, lamin, endothelin, NO and VWF Also posses bound enzymes ACE and ACE2 to control BP
Von Willebrand disease	Genetic disease where VWF is not produced Problems with blood clotting VWF normally binds to factor VIII which gets degraded in absence
Angiotensin Converting Enzyme	ACE is a central component of the RAS system Predominantly in lung but is fairly ubiquitous Controls BP - converts angiotensin I to active vasoconstrictor Angiotensin II which increases BP
ACE2	Lowers BP by catalysing hydrolysis of Angiotensin II into Angiotensin 1-7 a vasodilator Counteracts ACE - disruption in balance leads to unregulated BP
ACE inhibitors and ARBs	Lowers arteriolar resistance and increase venous capacity Lowers BP Used widely for treatment of CVD
ACE2 in Covid	Binds to ACE 2 - promotes internalisation of viral receptor and virus downregulating ACE2 impacting BP Knocking down ACE2 or introducing sACE2 could reduce entry of covid to cells But would affect BP control
Protective role of tunica media	Concentric cell layers of smooth muscle, elastic fibres, Type III collagen and proteoglycans Collagen provides restraint - absence leads to aneurysm and EDS type IV (mutation in COL3A1 gene) Larger arteries have larger external lamina
Composition of tunica adventitia	Fibroblasts Type I collagen Elastic fibres Small blood vessels Adipose tissue
Vasa Vasorum	Blood supply of the walls of larger arteries - too large for diffusion Small arteries enter vessel walls and branch Serve cells located in tunic media and adventitia with blood Prevalent in veins as venous blood contains less oxygen and nutrients
Classification of arteries	Elastic - conducting Muscular - distributing Arterioles
Elastic arteries	Walls of pulmonary arteries and aorta have to withstand most pressure and changes in pressure Walls have a thick layer of elastic tissue for this - appear yellow Further from the heart amount of elastin decreases and media becomes more muscular
Muscular arteries	Include most vessels arising from aorta Muscle tone maintains pressure Some have 3-4 layers of SM while some have up to 40 Tunica intima is thinner and internal elastic lamina more prominent Allow selective distribution of blood
Atherosclerosis	A chronic disease with thickening, hardening, loss of elasticity and occlusion of arteries Impaired circulation and ischemia leading to heart attack and stroke Develops with age, hypertension, diabetes, smoking and high LDL
Atherosclerosis affects large vessels	Artery wall thickens as a result of accumulation of fatty materials Promoted by LDL which carry cholesterol to tissues Macrophages injects LDL cholesterol turning into foam cells and plaques develop
Cholesterol	Modified steroid in membranes Precursor for steroids, bile acids and Vit D Produced by liver - statins block this Transported by lipoproteins - HDL and LDL
Role of LDL and HDL	LDL transports cholesterol to cells and tissues HDL reduces, reuses and recycles LDL cholesterol by transporting it to the liver to be reprocessed High HDL correlated with better health outcomes Low HDL associated with atheromatous disease
Development of Atherosclerosis	Initiates with endothelial damage - endothelium adhesion molecules capture leukocytes LDL invades and becomes oxidised Macrophages take up LDL - accumulations of cholesterol engorged macrophages form foam cells - fibrous plaques develop and rupture
Result of plaques	Fatty material develops on walls Thickens, hardens and blocks arteries Platelet aggregation and clot formation Predisposes to narrowing, clot formation and weakness Calcification at the outer base
Coronary Heart Disease	Nutrients and oxygen for heart muscle not provided Heart attack Chest pain, angina, shortness of breath, sweating, left back and arm pain, dizziness Most common risk factors are smoking, family history, hypertension, obesity, diabetes
Ischemic stroke	When a blood vessel supplying brain becomes blocked Thrombosis - obstruction by locally forming clot Embolism - obstruction by an embolus formed elsewhere e.g. pulmonary embolism where pulmonary artery is blocked
Haemorrhagic stroke	When a blood vessel bursts leaking blood into the brain
Results of ischemic stroke	Shortage of blood supply results in shortage of oxygen, glucose and other blood borne fules Results in tissue
Treatment of Ischemic stroke	Timely diagnosis and treatment are critical as damage evolves rapidly over firsts few hours First goal of acute ischaemic stroke treatment is to restore blood flow by dissolving the clot Thrombolysis - TSA needs to be injected in first 4.5 hours
Thrombectomy	Putting thin tube into patients blood vessel in periphery and feeding it up to clot in brain A wire mesh is wrapped around the clot and it is pulled out Restores normal blood flow to brain if done in first 6 hours Costs around £12000
Anuerysm	A sac like dilation in the wall of a vessel Risk factors; atherosclerosis, hypertension, Marfan syndrome, EDS, Syphilis Vessel wall is damaged and ruptures easily Massive blood loss or death - Abdominal Aorta Anuerysm
Gangrene	Results when tissue becomes necrotic due to reduced blood supply Caused by blood vessel disease precipitated by infection, diabetes, atherosclerosis, surgery Reduced blood supply leads to cell death Treatment - surgical debridement
General scheme if microvasculature	Discontinuous smooth muscle cells - surround arterioles and small veins Pericytes support these vessels and can differentiate into fibroblasts, smooth muscle cells or macrophages
Pericytes	Multitasking cells with plasticity and a range of activities Support blood vessels - promote vessel stabilization Regulate vascular tone and tissue perfusion Act as macrophages Key in wound healing -loss leads to hyper dilated and haemorrhagic vessels
Angiogenesis	A normal and vital process in growth/development, wound healing and granulation tissue Also a fundamental step in transition of tumours from dormant to maligant A target for combatting tumour progression
Arterioles	Arteries with a diameter of <0.1mm Width of wall equal to diameter of vessel One or two layers of SM Peripheral resistance vessel - controls arterial blood pressure Controls distribution of blood to whole capillary beds Controlled by SNS
Pre-capillary sphincters	A ring of muscle surrounding a blood vessel at the junction between an arterioles and a capillary Controlled by factors which reflect tissue metabolism Can open and close a capillary - facilitates shunting
Types of capillary	Continuous Fenestrated Sinusoidal
Capillaries	50 um length and 8-10 um diameter Squamous epithelium Pericytes along outside involved in regulation of blood flow After injury pericytes may differentiate into endothelial cells No smooth muscle or vasomotor activites
Continuous capillaries	Muscle, nervous and connective tissue where there is no protein passage Have junctional complexes - tight control of trans-endothelial transport Barriers e.g. blood brain barrier Prevent passage of molecules Substances moved by active transport
Fenestrated capillaries	Pores 60-80 nm in diameter Pancreas, intestine, kidney and endocrine glands where there is no need for protein passage Basement membrane in kidney specialised for filtration Pores bridged by diaphragms Permeable to small ions and other molecules
Sinusoidal capillaries	Large fenestrae without diaphragms permit enhanced exchange between blood and tissue Bone marrow, liver, spleen, lymphoid organs and endocrine glands Immune system - allows leukocytes to pass between tissues Irregular channels - conform to structure
Bypassing of capillaries	Channels in vascular system which allow capillary beds to be bypassed Common in the skin for thermoregulation Common in gut to allow perfusion of liver when gut circulation is shut down during fight or flight
Anastomosis	Arterio-arterial e.g. circle of willis in brain Veno-venous e.g. portacaval Arterio-venous e.g. finger tips Serve as back up routes for blood but can be pathogenic e.g. fistula Can be induced surgically to bypass diseased vessel
Veins	Classified based on size Low pressure - less muscle Same 3 layers as arteries but less developed muscle and elastic layers Connective tissue more pronounced Tunica intima/media boundary less clear Valves in medium veins
Small veins and venules	Blood goes from capillary beds to postcapillary venules Walls similar to capillaries with thin endothelium surrounded by reticular fibres and pericytes Site of migration of neutrophils, macrophages especially in inflammation - diapedesis
Medium veins	Less than 1 cm in diameter Smooth muscle cells of tunica media loosely organised with collagen fibres and fibroblasts Tunic adventitia thickest - composed of longitudinally arranged collagen bundles and elastic fibres
Large veins	Low pressure high capacitance allows large amounts of blood to be stored - 60% of total Have valves to prevent backflow Thin tunica media Well developed smooth muscle Well developed tunica adventitia
Varicose veins	Valves in veins no longer work properly allowing blood to move backwards Results from loss of muscle tone, degeneration of vessel wall and vascular incompetence May also occur in lower oesophagus = oesophagus varices Terminus of anal canal
Deep vein thrombosis	Blood clots in veins most often occur in legs Caused by; damage to lining of vein, clotting conditions e.g. factor V mutation, immobility and post surgery Blood clot can break off and travel to lungs - pulmonary embolism Treated by anticoagulants
Vasculitis	Arteries and veins affected Though to be autoimmune inflammation of vessels Can be a main feature or an accompanying symptom Many symptoms Treatment with immunosuppressants
Blood vessel specialisations	Blood brain barrier Blood air barrier Kidney filtration barrier
Blood brain barrier	Composed of tight junctions, astrocytes, pericytes and microglia Prevent paracellular and transcellular diffusion Dyes injected into the blood accumulate in organs but not the brain Astrocytes have end feet which form part of the barrier
Blood air barrier	Gases diffuse via passive diffusion Cytoplasm of alveolar cells, endothelial cells and fused basal laminae of these cells form the barrier
Kidney filtration barrier	Thin endothelium of capillary with fenestration Specialised basal lamina Podocytes - urinary capsule lining cells Thin endothelial cells for filtration Regulates filtration

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