vascular system 2: diseases affecting the arterial system · fibrous capsule. the plaques are prone...

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58Nursing Times [online] May 2018 / Vol 114 Issue 5 www.nursingtimes.net

The vascular system is a complex network of blood vessels con-necting the heart with all other organs and tissues in the body

via the arteries (which bring oxygenated blood to the organs and tissues) and veins (which return to the heart with deoxygen-ated blood). Its structure, physiology and function are described in the first article of this three-part series.

This article, the second in the series, reviews the common diseases affecting the arteries. In many of them, the underlying pathogenic process is atherosclerosis.

AtherosclerosisThe general term for the hardening of the arteries is arteriosclerosis – from the Greek arterio (artery) and skleros (hard). Arterio-sclerosis can have different causes, including blood vessel calcification (more common in older people), but is most com-monly due to atherosclerosis.

The disease is particularly prevalent in the Western world and is the single largest cause of arterial disease. It affects the

larger and medium arteries, such as the aorta and the coronary, cerebral and peripheral arteries (Zhao, 2018). These become hardened and lined with athero-sclerotic ‘plaque’ – also known as ath-eroma, which restricts the supply of oxy-genated blood to the organs and tissues.

The progressive formation of atheroma in the arterial vessels can begin in child-hood. It is the result of endothelial cell dys-function, lipid deposition and complex inflammatory processes.

The squamous epithelial cells that form the endothelium (innermost layer of the vessel wall) are delicate and vulnerable to hyperlipidaemia, hyperglycaemia (from diabetes), hypertension and toxins such as cigarette smoke, which culminates in low-grade inflammation. Once injured, the endothelial cells change shape and their properties are altered; they become increasingly permeable to fluids, lipids and immune cells.

Monocytes are immune cells that survey the integrity of the endothelium. If they detect damage, they go to the damaged

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Keywords Atherosclerosis/Cholesterol/Ischaemia/Angina/Stenosis/Vasculitis This article has been double-blind peer reviewed

Key points In atherosclerosis, a lipid-rich plaque forms on the innermost layer of the artery wall

Atherosclerosis plays a role in many diseases where there is narrowing or blockage of the arteries

Modifiable risk factors for arterial disease include hyperlipidaemia, diabetes, hypertension and smoking

In the coronary arteries ischaemia causes chest pain, while in the arteries of the lower limbs it causes claudication

Vasculitides are diseases of blood vessels caused by immune-mediated processes

Vascular system 2: diseases affecting the arterial system

Author Selina Jarvis is a research nurse and former Mary Seacole development scholar at Kingston and St George’s University of London and King’s Health Partners (Guy’s and St Thomas’s Foundation Trust).

Abstract With its arteries and veins, the vascular system connects the heart with all other organs and tissues and circulates blood around the body. It can be affected by diseases with different pathogenic mechanisms. Many arterial diseases are underpinned by atherosclerosis, while some have genetic origins or are immune-mediated. This article, the second in a three-part series, describes the pathophysiology of the main arterial diseases. The first article in the series covered the anatomy and physiology of the vascular system, and the third will discuss diseases of the venous system.

Citation Jarvis S (2018) Vascular system 2: diseases affecting the arterial system. Nursing Times [online]; 114: 5, 58-62.

In this article...● Pathogenesis, types of and risk factors for arterial diseases● Cellular mechanism of atherosclerosis● Vasculitides, a rarer type of vascular disease

Clinical PracticeSystems of lifeVascular system



atherosclerotic narrowing, and atheroscle-rosis is the most common cause of coro-nary artery disease (CAD) (Jarvis and Saman, 2017).

Narrowing or blockage of the coronary arteries causes ischaemia, which often man-ifests as chest pain. In stable angina, there is a fixed flow defect caused by a stable ath-eroma restricting blood supply to the myo-cardium. When a patient with stable angina undertakes exercise or is under stress, there is a mismatch between blood supply to, and blood demand of, the myocardium, which causes chest pain. Upon rest or stress reduc-tion, the symptoms resolve.

In unstable angina (UA), which belongs to a spectrum of conditions called acute coronary syndrome, the atheroma pro-gresses further and chest pain may also occur at rest and become more frequent and/or more severe. However, in the case of UA, there is no detectable myocardial cell necrosis when assessed using biochemical tests such as troponin levels (a myocardial protein used as a marker of damage).

or due to atherosclerotic plaque rupture and formation of new thrombus, which migrates and affects cerebral blood flow. Blockage of the arteries supplying the lower limbs has similar effects, causing peripheral arterial disease (PAD).

The atheroma tends to form at sites where arteries bend, branch off or bifur-cate (for example, where the two common carotid arteries divide into the two internal and external carotid arteries).

Conversely, stretches of straight blood vessel often remain atheroma free, com-pared with areas where there is disturbed blood flow. Such sites are characterised by alterations in blood flow and shear stresses (caused by frictional forces by the blood flow) on the endotheliumm, which plays a role in atherosclerosis (Zhao, 2018).

Coronary artery diseaseThe coronary arteries provide oxygenated blood to the heart (myocardium). The right and left coronary arteries and their branches are easily affected by

area, insert themselves beneath the layer of cells and mature into macrophages. These trap cholesterol carriers circulating in the vessels – particularly oxidised low-density lipoproteins (LDLs) – and become lipid-laden foam cells (Fig 1), which in turn release a plethora of inflammatory sub-stances and growth factors. This further encourages atheroma formation.

Cholesterol accumulates not only in foam cells, but also in the atheroma itself, where it forms a lipid core. Lipid-rich plaques contain inflammatory cells, smooth muscle cells, cellular debris and a fibrous capsule. The plaques are prone to rupture, which can ultimately block arte-rial blood flow, leading to a dramatic mis-match between supply to, and demand of, the affected organs or tissues.

In the heart, aberrations in arterial blood flow can lead to myocardial infarc-tion (MI). In the arteries supplying the brain, atherosclerosis can lead to a cere-brovascular accident (stroke), either because the arteries have become stenotic

Clinical PracticeSystems of life

Fig 1. Mechanism of atherosclerosis

Smooth muscle cell migration

Monocyte adherence

Endothelium

Matrix

Smooth muscle cell layer

T-lymphocyte activation

Foam cell differentiation; fatty streak formation

External elastic membrane

Monocyte adherence and transendothelial migration

Activated resident macrophage

Rolling

Secretion of inflammatory molecules

Adhesion

Transendothelial migration

Monocyte differentiation into macrophage and lipid-laden foam cell

Monocyte

Monocyte

Circulating cell recruited to inflammatory site

Macrophage

Activated phagocyte; secretes inflammatory molecules, free radicals and proteases, and scavenges lipoprotein particles

Foam cell

Lipid-laden; plays active role in cholesterol metabolism and secretes macrophage products



cognitive decline (Bivard et al, 2018; Ay and Koroshetz, 2006).

One cause of haemorrhagic stroke is intracranial aneurysm, which results from a weakness of the vascular wall, ballooning and becoming prone to rupture. Intracra-nial aneurysm causes most cases of suba-rachnoid haemorrhage (SAH); 75% of patients with SAH are under 65 years of age. Berry aneurysms are responsible of 85% of cases of SAH; they are referred to as berry aneurysms because the dilated vessel resembles a ‘berry on a stem’ and these may occur in the Circle of Willis (Fig 2) (Newby et al, 2014).

In acute cerebral infarction, there is neuronal cell necrosis, which can cause permanent damage unless reperfusion with thrombolytics (‘clot-busting’ drugs) is undertaken urgently.

In transient ischaemic attack (TIA), there is transient ischaemia usually lasting two to three hours, however this can last up to 24 hours. TIAs can be a predictor of future strokes, especially if risk factors are not managed. It was previously thought that TIAs did not cause any lasting neuro-logical damage, however, neuroimaging has shown that, in 50% of patients, there are micro-infarctions associated with

Complete abrogation of the coronary blood supply can result in irreversible damage to the region of the myocardium supplied by the affected artery. This often occurs due to the rupture of an atheroma in the vessel wall, which triggers the for-mation of a thrombus.

The thrombus causes acute ischaemia, which, if left untreated, can lead to myo-cardial cell necrosis and MI involving either the whole thickness of the heart muscle (ST elevation MI) or only part of the cardiac wall (non-ST elevation MI). In case of ST elevation MI, without reperfusion within 6-12 hours, there will be irreversible damage, cardiac remodeling, arrhythmias, heart failure and a high risk of death (Jarvis and Saman, 2017).

Cerebrovascular diseaseThe brain receives blood from two main paired arteries; the internal carotid and vertebral arteries, and where their branches terminate (at the base of the brain) form the anastomotic Circle of Willis supplying different regions of the brain (Fig 2).

Cerebrovascular disease (CVD) includes events, such as cerebrovascular accidents (strokes), in which brain tissue becomes starved of oxygen and risks permanent damage. This can occur either due to a vessel occlusion that alters the intracere-bral blood supply or haemorrhage caused by vessel rupture.

Causes of CVD can be further described as: ● Intrinsic blood vessel defect secondary

to atherosclerosis, inflammation or malformation, or due to aneurysm (abnormal widening of an artery) or dissection (tear in the intimal layer of an artery wall);

● Blockage of an intracranial blood vessel by an embolus that has migrated from extracranial vessels after – for example, clot formation in the heart due to atrial fibrillation or atheromatous plaque rupture and thrombus formation in the carotid arteries;

● Inadequate cerebral blood flow and decreased perfusion due to an injury or hyper-viscosity of the blood (for example, in polycythaemia);

● Blood vessel rupture causing haemorrhage.Around 20% of strokes are caused by

brain haemorrhage (haemorrhagic stroke), while 80% are due to a blockage from thromboembolic disease (ischaemic stroke) (Caplan, 2018). Table 1 lists the dif-ferent types of stroke and the risk factors.


Table 1. Stroke types and risk factorsHaemorrhagic stroke Risk factors

Intracerebral haemorrhage Hypertension, trauma, vascular malformations, bleeding diatheses, illicit drug use

Subarachnoid haemorrhage Smoking, hypertension, genetic susceptibility, cocaine use

Ischaemic stroke Risk factors

Ischaemic (thrombosis) Atherosclerotic risk factors (for example, age, gender, smoking and diabetes); history of stroke or transient ischaemic attack

Ischaemic (embolic) Atherosclerotic risk factors (for example, age, gender, smoking and diabetes); history of heart disease, atrial fibrillation, valvular disease, endocarditis

Source: adapted from Caplan, 2018

Fig 2. Circle of Willis

Anterior communicating artery

Horizontal segment of anterior cerebral artery

Frontal lobe

Horizontal segment of middle cerebral artery

Temporal lobe

Right posterior communicating artery

Superior cerebellar artery

Pontine branches

Right anterior inferior cerebellar artery

Right vertebral artery

Basilar artery

Left posterior communicating artery

Optic chiasm



Peripheral arterial diseasePeripheral arterial disease (PAD) refers to arterial syndromes caused mainly by ath-erosclerotic obstruction in the arteries of the lower limbs. Risk factors for PAD are therefore similar to those for atheroscle-rosis (smoking, diabetes, hypertension and hyperlipidaemia). Causes of PAD are listed in Box 1.

PAD can be classified according to disease severity; its prevalence increases from the age of 40 and is highest in people with a history of CAD and/or CVD (Arm-strong, 2017).

Over time, PAD causes luminal nar-rowing of the blood vessels, limiting blood flow to the tissues and leading to chronic ischaemic pain in the lower limbs. More advanced PAD can lead to arterial obstruc-tion resulting in pain at rest, ulceration and compromised tissue viability.

Ischaemic leg pain that is relieved by rest (usually resolving within around 10 minutes) and occurs at particular walking distances is referred to as intermittent claudication. Patients with PAD may expe-rience pain in the feet, calves, thighs or buttocks, according to which part of the peripheral arterial blood supply is affected:● Buttock or hip claudication is due to

PAD in the aortoiliac vessels;● Thigh claudication is due to PAD in

the common femoral artery;● Calf claudication is due to PAD in the

superficial femoral artery (upper two- thirds of the calf ) and popliteal artery (lower third of the calf );

● Foot claudication is due to PAD in the tibial and peroneal arteries.Persistent ischaemia can damage the

peripheral nerves, which can in turn lead to neuropathic pain and/or loss of sensa-tion – potentially causing functional impairment, infections and foot ulcera-tion (McDermott, 2015). PAD is more common in people with diabetes than in those without it (9.5% and 4.5%, respec-tively), with PAD exacerbating peripheral neuropathies, which are also more common in people with diabetes.

Patients who already have stenotic arteries in the limbs are at risk of devel-oping acute limb ischaemia, which may be caused by a clot (thrombus) in the stenotic vessel, trauma or thromboembolism and this is a surgical emergency.

The clinical features of acute and chronic limb ischaemia are shown in Box 2.

VasculitidesThis refers to inflammatory diseases affecting the arteries and capillaries

are sometimes caused by aortitis linked to conditions such as syphilis, or by diseases such as Takayasu’s arteritis, Reiter’s syn-drome, giant cell arteritis and ankylosing spondylitis (Newby et al, 2014).

Aortic dissectionThe aorta is exposed to high pulsatile blood pressures and shear stresses, and so may be more vulnerable to rupture than any other blood vessel. A tear in its intimal layer can cause aortic dissection, the majority of which occur within 10cm of the aortic valve.

The tear in the intimal layer is the initial insult. As blood flows through it, there is subsequent degeneration of the medial layer and creation of a false lumen along-side the true lumen of the aorta.

Blood flows between the tunica intima and media eventually separating these layers causing a false lumen. This diver-sion of blood flow from its normal course means that, eventually, blood flow through some branches of the aorta may be reduced. This leads to reduced blood flow in the coronary, brachiocephalic, intercostal, visceral, renal and iliac vessels (Safi, 2017).

Aortic dissection may be congenital or acquired, and is more common in people with hypertension. As mentioned above, genetic connective tissue disorders such as Marfan syndrome and Ehlers-Danlos syn-drome can increase the risk of aortic dis-section. Patients with congenital aortic stenosis and metabolic disorders such as homocystinuria are also at increased risk. Pregnancy may be a risk factor in women presenting with aortic dissection before the age of 40.

Aortic dissection can be categorised based on whether it affects the ascending or the descending aorta – or both.

Some cases cases of berry aneurysm occur in association with adult polycystic kidney disease or with other genetic dis-eases such as Ehlers-Danlos syndrome (a collagen disorder). In the remaining cases, 5% may be due to an arterio-venous malformation and 10% of cases of SAH may be due to non-aneurysmal causes

Aortic diseaseDiseases that affect the aorta – the largest artery in the body – can lead to aneurysm or dissection or can cause aortitis – inflammation of the aorta. In many cases a decision must be made for patients to have either active surveillance or prompt intervention. In some of these diseases, atherosclerosis is the key underlying pro-cess, but the aorta is also affected by many diseases with a completely different pathogenesis.

An aortic aneurysm refers to abnormal widening of the aorta, which makes the vessel prone to rupture. An aortic dissec-tion is when there is a tear in the tunica intima (innermost layer) of the vessel wall which allows blood to track between the tunica intima and tunica media. Both can affect either the thoracic aorta, or the abdominal aorta – or both.

Aortic aneurysmAn aorta with an aneurysm is more than 1.5 times the anteroposterior diameter expected for the patient’s age and gender (Sheehan, 2017). Although aortic aneu-rysms can occur in the thoracic segment of the aorta, in 90% of cases they are abdom-inal and situated below the renal arteries.

Most aortic aneurysms are secondary to atherosclerosis, but they can also be due to cystic medial necrosis (CMN), a completely different process involving cyst-like lesions and the accumulation of a baso-philic ground substance.

In CMN, the aorta shows signs of col-lagen and elastin loss from its tunica media and tunica externa (external layer of the vessel wall), as well as marked smooth muscle loss. The aorta becomes vulnerable and, in case of abdominal aortic aneurysm (AAA), is at risk of rupture. Without prompt diagnosis and intervention, a rup-tured AAA will lead to massive haemor-rhage and death.

Some genetic connective tissues disor-ders, such as Marfan syndrome or Ehlers-Danlos syndrome, can affect the elasticity of the aorta, leading to CMN and putting patients at risk of aortic aneurysm (and aortic dissection). Other genetic diseases may also be implicated. Aortic aneurysms


Box 1. Causes of peripheral arterial disease

●Aortic coarctation or dissection●Arterial embolism or thrombosis●Vasospasm●Trauma●Arterial tumour●Rarer causes: Takayasu’s arteritis,

temporal arteritis, thoracic outlet obstruction, Buerger’s disease, adventitial cystic disease, occluded limb aneurysm, popliteal artery entrapment, iliac endofibrosis, ergot toxicity, radiation fibrosis, retroperitoneal fibrosis



stroke and treatment options. Current Treatment Options in Cardiovascular Medicine; 8: 3, 193-200.Bivard A et al (2018) Transient ischemic attack results in delayed brain atrophy and cognitive decline. Stroke; 49: 2, 384-390.Caplan LR (2018) Overview and evaluation of stroke. Bit.ly/UtDStrokeCascieri MA (2002) The potential for novel anti-inflammatory therapies for coronary artery disease. Nature Reviews Drug Discovery; 1: 2, 122-130.Jarvis S, Saman S (2017) Diagnosis, management and nursing care in acute coronary syndrome. Nursing Times; 113: 3, 31-35.Jennette JC et al (2012) Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis and Rheumatology; 65: 1, 1-11.Merkel PA (2018) Overview of and approach to the vasculitides in adults. Bit.ly/UtDVasculitidesMcDermott MM (2015) Lower extremity manifestations of peripheral artery disease: the pathophysiologic and functional implications of leg ischemia. Circulation Research; 116: 9, 1540-1550.Morasch MD (2017) Vertebral artery revascularization. Bit.ly/UtDRevascularization Newby DE et al (2014) Cardiovascular disease. In: Walker BR et al (eds) Davidson’s Principles and Practice of Medicine (22nd edn). Edinburgh: Churchill Livingstone.Safi HJ (2017) Aortic dissection. BMJ Best Practice.Sheehan MK (2017) Abdominal aortic aneurysm. BMJ Best Practice. bestpractice.bmj.com/topics/en-gb/145Zhao XQ (2018) Pathogenesis of atherosclerosis. Bit.ly/UtDAtherosclerosisPathogenisis

Table 2 lists the main types of systemic vasculitides.

Their consequences depend on the size of the blood vessels they affect, how many vessels are involved, and/or the target organ. In many diseases that cause vascu-litis, it remains unclear what the trigger is or why there is a predilection for a par-ticular blood vessel or organ but these dis-eases have the common feature in that in most cases they occur due to an immune-mediated process.

ConclusionAtherosclerosis is the often underlying process in the main arterial diseases (coro-nary artery, cerebrovascular, aortic and peripheral arterial disease). The rarer vas-culitides have a different pathogenesis but potentially similar clinical manifestations.

The incidence of arterial diseases is growing due to unhealthy lifestyles and the ageing of the population, increasing the burden on the healthcare system. Since many of them are due to atherosclerosis, active primary and secondary prevention through the management of modifiable risk factors is a priority. In some cases of arterial disease, prompt recognition of emergencies and referral for multidiscipli-nary care are needed. NT

ReferencesArmstrong E (2017) Peripheral arterial disease. BMJ Best Practice. bestpractice.bmj.com/topics/en-gb/431Ay H, Koroshetz WJ (2006) Transient ischemic attack: are there different types or classes? Risk of

mainly. The vasculitides are defined by the presence of inflammatory cells in the vessel walls leading to damage and destruc-tion of the wall (Merkel, 2018). They have a completely different pathogenesis to ath-erosclerosis, but in some cases can still produce similar clinical manifestations.

Vasculitides are a heterogeneous group of diseases driven by autoimmune pro-cesses. Often associated with rheumato-logical diseases, they include a broad range of diseases, some of which have a predilec-tion for either a particular size of blood vessel or a particular organ. Classification of the vasculitides is based on the predom-inant size of the vessel affected but there may be some overlap with certain vascu-litides (Merkel, 2018).

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Vascular system series DatePart 1: Anatomy and physiology AprPart 2: Diseases affecting the arterial system MayPart 3: Diseases affecting the venous system Jun

Box 2. Clinical features of limb ischaemia

Acute limb ischaemia●Pain●Pale limb●Pulselessness●Extremely cold limb (this feature

can be unreliable as limb takes temperature of the environment)

●Paraesthesiae (a feature of irreversible ischaemia)

●Paralysis (a feature of irreversible ischaemia)

Chronic limb ischaemia●Diminished or absent pulse●Bruits suggesting turbulent flow,

no association with degree of vessel narrowing

●Reduced skin temperature●Pale skin, worse on elevation●Muscle wasting●Skin changes, nail changes

“Atherosclerosis is the often underlying process in the main arterial diseases”

Table 2. Main types of vasculitides Large vessel vasculitis

Medium-size vessel vasculitis

Small vessel vasculitis Variable-size vessel

● Takayasu’s arteritis

● Giant cell arteritis

● Polyarteritis nodosa

● Kawasaki disease

ANCA-associated vasculitis:● Granulomatosis with polyangiitis (Wegener granulomatosis)● Microscopic polyangiitis● Eosinophilic granulomatosis with polyangiitis

(Churg-Strauss syndrome)Immune-complex small-vessel vasculitis● Cryoglobulinaemic vasculitis● Anti-glomerular basement membrane disease● IgA vasculitis (Henoch-Schönlein purpura)● Hypocomplementemic urticarial vasculitis

● Cogan’s syndrome● Behçet’s disease

ANCA = antineutrophil cytoplasmic autoantibody

Source: adapted from Merkel, 2018; Jennette et al, 2013

vascular system 2: diseases affecting the arterial system · fibrous capsule. the plaques are prone...

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