VASCULOPATHIES Flashcards
(34 cards)
What is Vasospasm?
Recall that endothelial cells release a host of mediators that modulate its smooth muscle wall. When arteries undergo uncontrolled contraction or dilation likely due to inappropriate mediator release, that’s called vasospasm. Of course, from a flow and perfusion perspective, the constriction is more problematic, potentially producing downstream ischemia. It’s important to note that structural changes to vessel wall (to be discussed in greater detail in these lectures) make it more susceptible in responding inappropriately to normal mediator-induced activities.
What are some clinical examples of Vasospasm?
Raynaud phenomenon • Young women (> men) • Episodic small artery vasospasm in fingers/toes, nose, ears, or lips • Results in blanching and cyanosis of fingers or toes • Precipitated by cold temperature and emotions • No underlying disease or pathology (primary) • Seen in association with other disorders (secondary) Subarachnoid hemorrhage due to aneurysm – may be followed by cerebral aneurysm in the 410 days after the hemorrhagic event, leading to ischemic stroke Variant (prinzmetal) angina – ischemia and potential myocardial infarction
An aneurysm is what? they can be classified by? True Versus False?
An aneurysm of a vessel wall is a localized weakness, which can get larger over time, and which can lead to very significant bleeding if it ruptures. Aneurysms can be developmental or congenital. Additionally, acquired aneurysms occur over time True aneurysms have structural changes in all 3 of the layers of the vessel wall – the intima, media, and adventitia. False aneurysms (pseudoaneurysms) typically have full-thickness wall disruption, but are ‘contained’ by the body’s responses of adhesion development, fibrosis, thickening of natural fascial planes, etc. that effectively (for a period of time anyway) wall off the process.
Pathophysiology of the acquired aneurysm?
• Atherosclerosis, causing severe wall remodeling • Hypertension-induced arteriolosclerosis, causing severe wall remodeling • Infection (generally bacterial), causing wall damage and weakness • Syphilis (specific bacterial agent), with its well described vascular pathology • Intrinsic wall quality is dysfunctional or poor (see Cystic medial necrosis below) • Inflammation-induced proteolytic activity, leading to collagen breakdown • Wall infiltration by, or excess production of, additional unhelpful extracellular matrix
Dissection of a vessel is what? often the result of?
Dissection can occur when any weakness in the arterial wall allows blood to enter and wedge open/expand the vascular layers through its high pressure quality. Dissections are often an outcome or sequela of earlier aneurysm formation, but they can occur without previous aneurysm.
Complications of either the aneurysm or dissection of a vessel?
Complications of either aneurysm or dissection are the following pathologic processes. Keep in mind that clinical findings will be very dependent on the actual artery involved.
- Rupture, with potentially catastrophic hemorrhage
- Thrombosis, due to alterations in blood flow mechanics and potential damage to the endothelial wall
Thoracic aortic aneurysm often leads to? Common pathophysiologies?
Aneurysm of aortic arch or descending thoracic aorta often leads to ballooning of the aorta in either a saccular or fusiform manner.
More common pathophysiology with thoracic aneurysms is the presence of…
- Hypertension-induced changes
- Intrinsically poor wall quality due to connective tissue disorders (Marfan and EhlersDanlos syndromes)
- Syphilis (tertiary) inducing obliterative, fibrosing destruction of the vasa vasorum, which eventually causes chronic ischemia to the aorta from the outside-in direction
Symptoms of a thoracic aortic aneurysm?
Symptoms of a thoracic aortic aneurysm are diverse because of the anatomy of the region.
- Difficulty in breathing or swallowing, depending upon pressure against the respiratory tree or esophagus
- Pain, if erosion into the bone of the ribs or vertebrae occurs
- Cardiac sequelae including 1) aortic insufficiency as valvular problems develop, and 2) myocardial ischemia due to changes in the anatomy of the coronary artery ostia
- hemodynamic compromise/hypovolemic shock if rupture occurs
Abdominal aorta aneurysm incidence? Risk factors? Common pathology findings?
The abdominal aorta developing aneurysmal distention is fairly common aging pathophysiology, with about 5% of men and 1-2% of woman having a > 3.0 cm AAA by age 65.
- Risk factors: male gender, smoking, age > 50 years
- Common pathology findings include moderate-severe atherosclerosis, although many of the aneurysm pathophysiologies describe above likely contribute
Clinical Symptoms of an Abdominal Aortic Aneurysm?
Clinical symptoms are also quite variable, depending upon where and how big the AAA becomes.
- asymptomatic (often)
- a pulsating abdominal mass
- enlargement and compression of adjacent structures (eg., ureter)
- obstruction/occlusion of, or extension into, a branch vessel leading to ischemia
- embolism, of either thrombotic or atherosclerotic material
- hemodynamic compromise or hypovolemic shock if rupture occurs
When can dissection occur in a vessel? What are the two patient profiles that are often seen with dissection? Where can dissections occur?
A dissection can occur when a tear/injury in the intima allows for high-pressure flow to tunnel through the layers of the vascular wall. Dissections can occur with or without dilation/aneurysm formation, but if it occurs in the setting of aneurysm, it’s likely because the aneurysm has already created an environment (endothelial or intimal injury as dilation progresses) that predisposes to a subsequent dissection; this is called a dissecting aortic aneurysm. Some important epidemiology associated with dissection:
- 2 patient profiles are often seen – 1) older men (50-60’s) with histories of atherosclerosis and hypertension, and 2) younger patients with connective tissue defects (Marfan syndrome)
- can occur anywhere along the length of the aorta, although usually within 10 cm of the aortic valve – these are the most clinically severe aortic dissections
What are some classic symptoms of dissection?
- excruciating pain with radiation to scapular region of the back, and with a distinct downward trajectory as the dissection progresses
- rupture into pericardial, pleural, or peritoneal cavities can be catastrophic
- cardiac-related sequelae are major complications o Aortic root and valve compromise aortic insufficiency o Bleeding to pericardial sac cardiac tamponade o Dissection into branch (such as coronary) vessels MI
Explain Cystic Medial Degeneration? Associated with? Locations affected? treatment?
Associated with Marfans, and a massive Baclofen overdose.
Caused by a mutation of the FNB1 gene on chromosome 15 that encodes the protein fibrillin-1, Marfan syndrome is an autosomal dominant disorder that is inherited ¾ of the time, and arises due to sporadic mutation ¼ of the time. Fibrillin-1 protein is necessary in maintaining a normal quality to the extracellular matrix, particularly the production and quality of elastic fibers. While clinical symptoms are quite variable, locations in the body where elastic fibers are prevalent are most likely affected.
- Aorta – cystic medial degeneration predisposing to aneurysm or dissection
- Cardiac valves – aortic or mitral insufficiency, mitral valve prolapse
- Ligaments and skeletal system – hyperflexible joints, disproportionately elongated limbs and digits, scoliosis, chest wall/sternum abnormalities
- Eye – ciliary zonules of the eye use elastic fibers to hold the lens in place, therefore, MFS patients have lens dislocation
Negative inotropic agents are primarily used to reduce general cardiac output, along with strenuous activity avoidance, and many MFS patients have normal lifespans.
Explain VEIN/VENULE PATHOLOGY AND VARICOSITY DEVELOPMENT?
Veins and venules don’t undergo a tremendous amount of pathology, and much of what does occur is structural remodeling over time. Veins/venules are the vascular system’s reservoir system, so they can undergo quite extensive dilation when needed. That ability to dilate is maximized and pathologized in certain situations, both of which eventually demonstrate increased intravascular venous pressure:
1) valves within the venule become incompetent over time (see right image), leading to backflow/retrograde flow.
2) downstream obstruction phenomena cause decreased venous outflow (think esophageal or rectal variceal development). Both of the situations lead to a venous paradigm/biologic truism…
Increased intravenous pressure leads to vascular dilation that becomes irregular and permanent which leads to varicosity development (varicose veins)
Explain Thrombophlebitis?
Inflammation and thrombosis are two broad pathologies that can occur to veins; either one can exist on its own (a phlebitis or a venous thrombosis), or either one can precede (and instigate) the other (thrombophlebitis).
Any etiology that increases the chances of either inflammation or thrombosis can cause a thrombophlebitis.
- Can be medically trivial
- Can be medically significant – note that a deep venous thrombosis often shows inflammation, and is a type of thrombophlebitis
- Can occur repeatedly in different locations – a migratory thrombophlebitis
What are hemiangioma’s? Occur where?
A benign collection of (generic) vessels defines a hemangioma, a neoplasm of endothelial cells.
Hemangiomas may occur on the skin surface or anywhere within the body. Hemangiomas can be congenital/visible at birth, but most are acquired by just living.
Explain the 3 common hemiangioma’s?
- Capillary hemangiomas are typically redder because the capillaries are usually more superficial (when on the skin)
- Cavernous hemangiomas are usually deeper in locations and have large, dilated vessels
- Lobular hemangiomas are usually capillary in nature, but arranged in lobules; these hemangiomas tend to occur after trauma or pregnancy
explain Angiosarcoma’s? tend to show up where?
This malignancy of endothelial cells, like a hemangioma, can occur almost anywhere in the body because of the distribution of endothelium. However, it tends to show up more likely in the skin, liver, breast, and soft tissue.
Angiosarcoma has some well-known patient settings (Boards alert) in which it arises:
- Older individuals without known risk factors, on the head, face, and scalp
- Breast - following radiation therapy
- extremities that have lymphedema, such as following lymph node regional dissections (ex: breast carcinoma treated with regional lymph node dissection)
- liver – following arsenic exposure (as is found in some pesticides)
- liver – following Thorotrast exposure (a radiology contrast agent used in the 30-50’s)
- liver – following polyvinyl chloride exposure (as is found in plastics)
What are the general features of immune mediated Vasculitis?
Here we will be discussing immune-mediated vasculitis, with purposeful ignoring of how an infection can sometimes induce either immune complex formation or cross-reactivity (molecular mimicry) responses. Rather, this category focuses on non-microorganism-induced immune reactions that lead to vascular wall inflammation; these vasculitic reactions may be any mixture of Type 2, Type 3, or Type 4 hypersensitivity pattern reactions.
• Autoantibody production and activity
o Anti-neutrophil cytoplasmic antibody (ANCA’s) – predominate types are IgG autoantibodies against proteinase 3 (PR3-ANCA/c-ANCA) or myeloperoxidase (MPO-ANCA/p-ANCA); there are other ANCA’s, but these two are the most important
o Anti-endothelial cell antibody
Finally, immune-mediated vasculitis can have different gross appearances, depending upon the tissue and disease in question. However, usually something in the petechiae-purpura spectrum is most typical.
When thinking about the immunemediated vasculitides, consider the following features: • General size of vessels affected (although this is highly variable) • Types of inflammation involved • Serum ANCA involvement? • Distinguishing clinical findings
What does this show?
Left image: petechiae dotting the surface of a so-called ‘flea-bitten’ kidney (Boards alert), which can be seen in several types of vasculitis that affect the kidney (also with SLE, Goodpasture syndrome, subacute endocarditis, malignant hypertension). In this case, the kidney is being affected by microscopic polyangiitis.
Explain Giant cell arteritis? (temporal arteritis) Demographic? Likely pathogenesis? Associated with?
This is the most common form of vasculitis in elderly patients. A biopsy from a section of the superficial temporal artery (while only part of the clinical workup) can be confirmatory.
- Female > male; most common in people over 70
- Associated with HLA-DR4
- Likely in pathogenesis: T-cell immune responses against vessel wall antigens, with the creation of autoantibodies against endothelial cell and smooth muscle cell antigen
Symptoms of giant cell arteritis? Affects which arteries? Treatment?
Symptoms are variable, but often include headache, pain in the head’s temporal regions, and constitutional symptoms (fever, malaise, and/or weight loss). However, ocular symptoms when present are the most the pressing concern. Occurs in 50% of patients abruptly Major reason to treat with corticosteroids (to prevent vision loss)
The distribution of vasculitis varies, but is typically described as involving medium – large arteries.
- Vertebral, and temporal arteries often involved
- Ophthalmic artery involvement can lead to diplopia and vision loss
- Aortic or aortic arch involvement can lead to giant cell aortitis (uncommon)
Microscopically what happens in giant cell arteritis?
Microscopically, a segmental granulomatous vasculitis is occurring, meaning not all portions of an affected vessels will appear diseased (and hence, a positive biopsy requires luck). . The elastic lamina becomes fragmented, and chronic and granulomatous inflammation will be apparent
Explain Takayasu arteritis? Features? Demographics?
This is the other major vasculitis that affects medium - large arteries. Some of the clinical features and pathologic findings can overlap giant cell arteritis, although they are different disease processes. Aorta and aortic arch involvement is characteristic, and leads to many of the clinical features.
- Loss of pulse in the upper extremities (‘pulseless disease’)
- Ocular manifestations: o Visual loss or field defects o Retinal hemorrhages
- Neurologic abnormalities
- Renal artery involvement causing renovascular hypertension
In contrast to giant cell arteritis, the classic patient with Takayasu arteritis is younger. • Most common in Asia and >> women • Affects younger adults, usually less than 40 y/o • Long term survival is possible, provided acute manifestations are controlled/not fatal
