ANEURYSM
Aneurysm is the abnormal dilation of a segment of arterial blood vessel or heart. There are two types: True and false aneurysm.
True aneurysm is the dilation of an intact, modified wall of arterial blood vessel or heart. E.g. atherosclerotic, syphilitic, & congenital aneurysm; ventricular aneurysm following transmural myocardial infarction. There are two types of true aneurysm: saccular and fusiform aneurysm.
Saccular aneurysms are spherical dilations, involving a limited segment of the vessel wall. Their sizes are between 5 and 20cm.
Fusiform aneurysms are diffuse dilations affecting an extensive segment of the vessel wall. Their diameter and length are up to 20cm
False aneurysm is the dilation of a vessel wall arising from a luminal defect, leading to extravascular hematoma still in connection with vascular lumen. E.g. ventricular rupture supported by pericardial scar tissues after myocardial infarction.
Dissection is the entrapment of blood between media layer of arterial wall, arising from a luminal tear and weak media.
Causes of aneurysm
Aneurysm may occur due to weakness of arterial wall or inherited defects in connective tissue synthesis.
- Atherosclerosis: causes ischemia & smooth muscle cells loss, thereby weakening inner media. (Main cause of abdominal aortic aneurysm)
- Hypertension: causes ischemia & smooth muscle cells loss, thereby weakening outer media. (Main cause of aneurysm of ascending aorta)
- Inflammatory infiltrates (e.g. in vasculitis): macrophages produce matrix metalloproteinases that breakdown components of ECM.
- Embolization of septic embolus in infective endocarditis, or adjacent suppurative infection.
- Tertiary syphilis: causes obliterative endarteritis in vasa vasorum of thoracic aorta, resulting in aortic media weakening. May also infect aortic valve annulus.
- Trauma
- Vitamin C deficiency: this causes an abnormal collagen fiber structure.
- Myocardial infarction
- Marfan syndrome: defective fibrillin-1 synthesis leading to elastin degradation & inelastic media.
- Loeys-Dietz syndrome: mutation of TGF-βR leading to less elastic fibers and more type 1 & 3 collagen fibers in media.
- Ehlers-Danlos syndrome: defective synthesis of vascular type III collagen.
- Congenital: berry aneurysm, especially in the circle of wills.
The examples of aneurysms include: abdominal and thoracic aortic aneurysm.
Abdominal aortic aneurysm
This is the abnormal dilation of a segment of the abdominal aorta, below the renal arteries & above its bifurcation. Atherosclerosis is the main cause. Other contributing factors include: inflammatory infiltrates; adjacent gastrointestinal infections (e.g. salmonella). They together weaken the media layer.
There is greater risk of rupture for aneurysms greater than 6cm in diameter. Lesions greater than 5cm require emergency surgical intervention, with bypass involving prosthetic graft. Abdominal aortic aneurysm also contains mural thrombus.
Clinical manifestations: palpable pulsating abdominal mass; rupture into peritoneal cavity or retroperitoneal tissues; obstruction of renal, iliac, mesenteric, & spinal arteries; ischemic injury of kidney, leg, G.I tract, spinal cord; embolization; ureteral or vertebral bone compression.
Thoracic aortic aneurysm
This is the abnormal dilation of a segment of the thoracic aorta. It commonly affects the ascending aorta. The main cause is hypertension. Hypertension causes hypertrophy of vasa vasorum, resulting in degenerative changes in aortic media. Other causes include: Marfan syndrome; Loeys-Dietz syndrome; syphilis.
Clinical manifestations: dyspnea from lung & airway compression; bone pain from compression of ribs & vertebral body; cough from irritation of recurrent laryngeal nerve; dysphagia due to impingement on esophagus; aortic valve dilation and insufficiency; myocardial ischemia from narrowing of coronary artery.
Aortic dissection
This is the entrapment of blood between the media layer of the aortic wall due to a luminal tear. This condition starts with a tear in the aortic lumen. In most cases, the cause of tear is unknown. It usually occurs on the ascending aorta. Aortic dissection may also rupture through the adventitia.
Risk factors include: hypertension in men between 40 & 60 years old; young people with connective tissue disorders (e.g. Marfan syndrome & others); diagnostic catheterization in hospitals; cardiopulmonary bypass.
Classification of aortic aneurysm: Type A (DeBakey type I & 2); Type B (DeBakey type 3). The more serous type A involves either the ascending & descending aorta (DeBakey type I) or only the ascending aorta (DeBakey type II).
Type B involves only the descending aorta, immediately just after the subclavian artery (DeBakey type III).
Clinical manifestations: severe chest pain that radiates to the back between the scapulae; rupture into pericardial, pleural, peritoneal cavity; cardiac tamponade; aortic insufficiency; myocardial infarction; extension of disection into carotid, coronary, mesenteric, iliac, renal arteries resulting in ischemia; compression of spinal arteries resulting in transverse myelitis.
VASCULITIS
Vasculitis is the inflammation of vessel walls ranging from large to small vessels, including capillaries. The main causes include: immune reaction & direct invasion of infectious agents. Other causes are: mechanical trauma; radiation.
Vasculitides represent a term that encompasses different diseases affecting vascular walls. Categorizing various vasculitides depends on these outcomes: size of vessel affected; granulomatous inflammatory reaction; necrotizing inflammation on vessel wall; organs affected; presence of autoantibodies; immune complex formation.
Classification of vasculitis include: non-infectious and infectious vasculitis. These classifications are important in initiating accurate therapy.
Causes of non-infectious vasculitis may be either of these:
- Immune complex reactions arising from drug hypersensitivity (e.g. penicillin, streptokinase) & viral antigens (e.g. hepatis B surface antigens).
- ANCA including MPO-ANCA & PR3-ANCA, which are antibodies against neutrophil cytoplasmic antigens-myeloperoxidase (MPO) & proteinase-3 (PR3) respectively. MPO is found in lysosomal granules, responsible for generating free oxygen radicals. PR3 is found mainly in neutrophil azurophilic granules. The activation of MPO-ANCA may come after usage of drugs (e.g. propylthiouracil). Induction of both MPO-ANCA & PR3-ANCA comes after infection, which causes release of MPO & PR3 from neutrophils.
- Anti-endothelial cell antibodies
The followings are examples of vasculitides arising from noninfectious causes:
Giant cell arteritis
This is a T-cell mediated, medial granulomatous inflammation of large to small arteries that results in intimal thickening. It primarily affects temporal artery. Other arteries it affects include: vertebral, ophthalmic artery & aorta. Age of onset is above 50 years.
Clinical manifestations: fever; headache; fatigue; weight loss; pain on palpation of temporal region of head; diplopia; total vision loss.
Diagnosis requires biopsy & histological investigation. Urgent treatment using corticosteroids and anti-TNF therapy.
Takayasu arteritis
This is an immune-mediated granulomatous inflammation of large and medium arteries resulting in transmural fibrosis and intimal thickening. It primarily affects the aortic arch. Other vessels may include: other parts of aorta; pulmonary artery; carotid artery; renal & coronary artery; brachiocephalic artery. Occurs in people less than 50 years old.
Clinical manifestations: fever; fatigue; weight loss; low blood pressure & weak pulses in upper extremity; claudication on movement; neurological problems; ocular problems; retinal hemorrhages; total blindness; pulmonary hypertension; myocardial infarction; systemic hypertension (renal artery thickening).
Polyarteritis nodosa
Polyarteritis nodosa is an immune-complex mediated necrotizing vasculitis, affecting medium or small arteries excluding (pulmonary artery, arterioles; capillaries).
Occasionally, it comes in association with chronic hepatitis B infection. It primarily affects renal, & visceral arteries (liver, G.I, heart). It usually occurs among young adults; however, it may also affect children and older adults.
Clinical manifestations: fever; fatigue; weight loss; systemic hypertension (renal artery involvement); abdominal pain and melena; peripheral neuritis & muscle pain.
Treatment with corticosteroids and cyclophosphamide are effective.
Kawasaki disease (mucocutaneous lymph node syndrome)
This is an immune-mediated inflammation which causes acute vasculitis, affecting large to small arteries. It usually affects children < 4 years old, and has a specific likeness for coronary artery.
Clinical manifestations: fever; conjunctival and oral erythema; edema and desquamative rash on hands and feet; erythema of palms and soles; cervical lymphadenopathy; coronary artery aneurysm; myocardial infarction; death.
Treatment is effective with immunoglobulin therapy and aspirin.
Microscopic polyangiitis
It is an immune complex-mediated acute systemic necrotizing vasculitis, which affects arterioles, capillaries, & venules. Unlike polyarteritis nodosa, the lesions present uniformly and can affect mucocutaneous tissues; kidney; lungs; heart; G.I tract.
It may occur in association with drug hypersensitivity (e.g. penicillin); infection (e.g. streptococci); tumor proteins.
Clinical manifestations: hematuria; hemoptysis; abdominal pain or bleeding; muscle pain or weakness; palpable purpura; extensive renal and brain complications.
To avoid complications, effective treatment with corticosteroids and cyclophosphamide improve survival.
Churg-Strauss syndrome (allergic granulomatosis & angiitis)
This is an immune-mediated, necrotizing & granulomatous inflammation affecting arterioles, capillaries, & venules. It mainly affects the upper & lower respiratory tracts. It may also affect other organs including heart, skin, kidney, G.I tract.
The causes may include: hyperresponsiveness to allergic stimuli; use of leukotriene receptor antagonists in asthmatic patients. Serology test occasionally identifies MPO-ANCA.
Clinical manifestations: allergic rhinitis; asthma; lung infiltrates; peripheral eosinophilia; palpable purpura; G.I bleeding; glomerulosclerosis; cardiomyopathy.
Granulomatosis with polyangiitis (Wegener granulomatosis)
This is an immune-mediated, necrotizing & granulomatous inflammation affecting medium to small arteries. It affects primarily both the upper and lower respiratory tracts and kidneys. It may affect other organs too. It affects more males than females at an average age of about 40 years.
Clinical manifestations: fever; chronic sinusitis; ulceration of the nose & nasopharynx; persistent pneumonitis with bilateral nodular and cavitary lesions of the lungs; glomerulonephritis; hematuria; rashes; joint pain; muscle pain; mononeuritis; polyneuritis.
Effective treatment strategy include: corticosteroids; cyclophosphamide; TNF-antagonists.
Thromboangiitis obliterans (Buerger disease)
This is a thrombosing, inflammatory reaction affecting medium to small arteries (tibial & radial artery). It may extend to the veins and nerves. Occurs in heavy cigarette smokers usually below the age of 35 years old.
Causes include: tobacco components; immune-mediated response. Disease is prevalent in Indian subcontinent, among Israelis and Japanese.
Clinical manifestations: superficial phlebitis; Raynaud type cold sensitivity in the hands; instep claudication with severe pain at rest; chronic ulceration of toes, feet, fingers resulting in gangrene.
Infectious vasculitis
Bacteria (e.g. Streptococci spp.) & fungi (e.g. Aspergillus and Mucor Spp.) are the main causes of infectious vasculitis. Ways vascular infections may occur include:
- Local tissue infection (e.g. bacterial pneumonia; bacterial pharyngitis)
- Adjacent abscess
- septicemia
- Embolization of septic embolus in infective endocarditis.
Vascular infections weaken arterial walls, causing mycotic aneurysm which results in thrombosis. Therefore, bacterial meningitis due to N. meningitides infection causes brain infarction.