Blood Vessels And Vasculitis Flashcards
General definition of Arteriosclerosis? What are the general patterns?
Means hardening of the arteries, it is a generic term for arterial wall thickening and loss of elasticity. There are three general patterns.
1.a Hyaline Arteriosclerosis where arterioles show homogenous pink hyaline thickening associated with luminal narrowing.
1.b Hyperplastic Arteriosclerosis where vessels exhibit concentric, laminated thickening of the walls with luminal narrowing.
2. Monckberg Medial Sclerosis is characterized by calcification of muscular arteries.
3. Artherosclerosis is the most frequent and clinical pattern
Artherosclerosis?
It is determined by a combination of acquired, cholesterol, smoking and hypertension, and inherited risk factors like LDL receptor gene mutation. An artheromatous plaque consists of raised lesion with a soft core of lipid covered by a fibrous cap. Beside mechanically obstructing blood flow, the plaques can rupture and lead to obstructive vascular thrombosis
Modifiable risk factors like hyperlipidemia, more specifically hypercholesterolomia, hypertension, cigarette smoking and diabetes mellitus are major risk factors for artherosclerosis.
Pathogenesis of Artherosclerosis?
It begins with endothelial dysfunction like enhanced leukocyte adhesion and altered gene expression, following that there is an accumulation of lipoproteins and macrophages. This causes a viscous cycle that stimulates the release of GF, cytokine and chemokines. Smooth muscle cells will start to synthesize collagen that stabilizes the artherosclerotic plaque which engulfs the lipids.
What are artherosclerotic plaques susceptible to?
- Rupture, Ulceration or erosion which can lead to thrombosis.
- Hemorrhage, the plaque can rupture and cause intra plaque hemorrhage.
- Artheroembolism, the plaque rupture can discharge debris into the blood stream.
- Aneurysm formation.
Certain types of plaques, like the ones with few SMC so a thin fibrous cap, are more likely to rupture.
Aneurysm? Classification?
Is a localized abnormal dilation of a blood vessel or the heart that may be congenital or acquired. When it involves at attenuated but intact arterial wall it is called a true aneurysm when it is a defect in the vascular wall leading to an extra vascular hematoma it is called a false aneurysm. The two most important causes of sporadic aortic aneurysms are artherosclerosis and hypertension.
They are classified base on their shape and size : Saccular aneurysms are spherical outpouchings involving only a portion of the wall, fusiform aneurysms are diffuse circumferential dilations of a long vascular segment
Other factors such as trauma, vasculitis, congenital defects can also weaken the vessel walls and lead to aneurysms.
Abdominal Aorta Aneurysm?
Occurs more frequently in men and smokers, develops rarely before 50 years old. Clinical manifestations include : rupture into the peritoneal cavity, obstruction of a vessel branching off from the aorta resulting in ischemic injury, Embolism. The risk of rupture is related to the size, most aneurysms expand at the rate of 0.2/0.3 cm per year. Since it is a systemic disease it is very likely that there is artherosclerosis in other vascular beds.
Thoracic Aorta Aneurysms?
Most commonly associated with hypertension. These can present with symptoms like : respiratory difficulties, difficult swallowing due to compression of esophagus, persistent cough and hoarseness due to compression of laryngeal nerves.
Aortic Dissection?
It occurs when blood separates the laminar planes to form a blood filled channel within the aortic wall. This can be catastrophic if the channel rupture and hemorrhages into adjacent spaces. This occurs in men ages 40 to 60 with hypertension or in younger adults with systemic or localized abnormalities of CT affecting the aorta like Marfan syndrome.
The dissections are classified in two types :
1. Proximal lesion, Type A, in one ascending aorta with or without involvement of descending aorta. DeBakey I and II.
2. Distal legions, Type B, beyond the subclavian artery. DeBakey III.
Clinically the classic symptom is sudden excruciating tearing or stabbing pain beginning in the anterior chest, radiating between the scapulae and progressing downward. Death is most likely caused by hemorrhage of fluid into pericardial, pleural or peritoneal cavity.
Vasculitis definition?
It is a general term for vessel inflammation. Major signs of inflammation are infiltration of leukocytes. The two most common pathogenic mechanisms of vasculitis are immune mediated inflammation and direct invasion of vessel walls by pathogens.
Immune Complex Associated Vasculitis?
This form can be seen in immunologic disorders such as SLE as the production of immune complexes deposit in vessels. Immune complex deposition is also implicated in Drug Hypersensitivity Vasculitis where the antibodies directed at drug modified proteins cause an immune reactions, and Vasculitis Secondary to Infections where antibodies and microbial constituents form complexes and deposit.
Antineutrophil Cytoplasmic Antibodies (ANCAs)?
They are a heterogenous group of autoantibodies that are directed against constituents, mainly enzymes, of neutrophils. ANCAs are useful diagnostic markers. Anti proteinase 3, Anti Myeloperoxidase are two markers which ANCAs bind to. ANCAs activate neutrophils and this causes the destruction of the vessel wall.
Giant Cell (Temporal) Arteritis ?
Most common form among older patients, it is a chronic inflammation of large arteries that principally affect extra cranial arteries of the head, especially the temporal, vertebral and ophthalmic arteries. This disorder stems from a T cell mediated immune response against vessel wall antigens. This causes pro inflammatory cytokines such as TNF and also a granulomatous response. There is intimal thickening and luminal diameter reducing. Symptoms are fever, fatigue, weight loss, headache, facial pain. Patients can become blind in 15% of the cases if left untreated. Corticosteroids or anti TNF therapies are effective.
Takayasu Arteritis ?
This is a rare granulomatous vasculitis of the medium and larger arteries characterized by ocular disturbances and weakening of the pulse inn the upper extremities. It causes transmural fibrous thickening of the aorta. It shares many attributes with GCV but the major difference is that it typically affects women under 40 yr old. Symptoms include the constitutional ones with reduced blood pressure, weak pulses in the carotid, ocular disturbances, blindness, neurological defects. The course of the disease is variable as it might progress rapidly or enter a quiescent stage.
Polyarteritis Nodosa (PAN) ?
It is a systemic vasculitis of small or medium sized arteries, typically involving renal and visceral vessels. 30% of patients have chronic hepatitis B and related immune complexes disorders. In the early phase polymorphonuclear cells infiltrate the vessel and the inflammation starts causing transmural necrosis. The chronic phase is where polymorphonuclear cells are substituted by macrophages and destroy the internal and external elastic lamina giving rise to fibrinoid necrosis. The course of the disease is frequently remitting and episodic. A classic presentation can involve hypertension due to renal artery involvement, abdominal pain, bloody stools caused by GI lesions. Untreated it is fatal however immunosuppressants cure or cause remission in 90% of cases.
Kawasaki Disease (Mucocutaneous Lymph Nodes Syndrome) ?
It is an vasculitis of large to medium sized arteries of infancy as patients in 80% of the cases are four yr old or younger. It stems primarily from coronary artery involvement that can cause thrombosis, aneurysms and acute MI. The pathogens is is unknown. A variety of infectious agents have been implicated, and the vascular damage is primarily mediated by T cells and macrophages. Clinically it presents with edema of hands and feet, erythema of palms and soles, rash, cervical lymph node enlargement. In 20% of untreated cases a series of cardiovascular problems arise. It resembles PAN as there is transmural inflammation and fibrinoid necrosis although less prominent that PAN.
