Cardiac Pathology - Vascular Disease Flashcards
What are the 5 main mechanisms of vascular disease?
- Gradual lumen obstruction (atherosclerosis (arteries/aorta) or arteriolosclerosis (arterioles))
- Sudden lumen obstruction (thrombosis, emoblism, or aortic/arterial dissection)
- Aneurysm/dissection (prefers larger caliber arteries (esp. aorta) with principle risk of rupture
- Vasculitis (spectrum of inflammatory diseases affecting aorta down to arterioles/capillaries/venules)
- Extrinsic vascular compression
What are examples of extrinsic vascular compression?
- Compartment syndromes: vascular collapse from surrounding hemorrhage/edema/inflammation. in a limited anatomic compartment (extremities, abdomen)
- -Vena cava syndromes (SUPERIOR & inferior): obstruction to caval flow usually caused by surrounding neoplastic adenopathy or occasionally from intra-caval tumor thrombus
What is MECHANISM #1 for vasculitis?
- VAST MAJORITY of most clinically morbid disease is ARTERIAL and dominated by ATHEROSCLEROSIS
- atherosclerosis prefers larger vessels (aorta, medium to large arteries): causing gradual lumen obstruction +/- aneurysmal dilation.
What are the main risk factors for atherosclerosis?
-Older age, male gender, post-menopausal women, FAMILIAL tendency (typically polygenic/multifactorial), hypercholesterolemia, hypertension, diabetes mellitus, and smoking
What is the pathogenesis associated with atherosclerosis?
- Only crudely understood
- “endothelial injury” leading to:
- -intimal collection of lipid-laden macrophages
- -Smooth muscle migration from media into intima
- -Intimal accumulation of extra-cellular matrix
- -WBCs as co-factors in above
What is an unstable plaque?
Inc. risk of surface rupture and platelet aggregation/fibrin clot formation = thrombosis - with risk of complete/sudden lumen occlusion
What is HTN or diabetes mellitus is present with atherosclerosis?
- Large vessel atherosclerosis is accelerated
- Arterioles become gradually obstructed (arteriolosclerosis)
What does arteriolosclerosis cause in HTN and diabetes?
Typically non-bypassable disease in the microcirculation: kidneys, retina, CNS/peripheral nervous system, heart and skin (e.g. diabetic foot ulceration)
-Untreatable small vessel vasculitis
What are the two types of hypertension?
95% - “essential” with multifactorial/polygenic/familial factors
5% - “secondary” (usually from reveal artery or adrenal disease) = potentially curable cases (DONT MISS)
What is malignant/accelerated HTN?
Medical emergency!!
Inc. risk of acute end-organ injury: heart, CNS, kidneys
What causes chronic end organ effects in HTN?
-Arteriolosclerosis, accelerated atherosclerosis and Inc. left ventricular and aortic strain: CAD/ischemic heart disease, thoracic aortic aneurysm, LVH/CHF, stroke (ischemic or hemorrhagic), retinopathy, nephropathy
What is the #2 mechanism of atherosclerosis?
-Sudden lumen occlusion
–> most common cause of life-threatening vascular events
Arterial: acute myocardial infarction, stroke, mesenteric ischemia/bowel infarction and acute leg ischemia/gangrene
What is an embolism?
Cardiac source until proven otherwise (e.g. left atrial or left ventricular thrombus)
Sudden lumen occlusion: Arterial:
- Acute myocardial infarction, stroke, mesenteric ischemia/bowel infarction and acute leg ischemia/gangrene
- Vast majority: unstable atheromatous plaque with rupture causing overlying occlusive thrombosis
- Embolism
- Aortic dissection can suddenly occlude orifices of exiting arteries
What happens in Veins with occlusive thrombosis?
- DVT: (usually iliofemoral veins) with risk of PE and sudden death: serum D-dimer testing and CT angiography
- Splanchnic venous thrombosis (mesenteric, portal/splenic, hepatic veins) = risk of bowel infarction or Budd-Chiari syndrome: Inc. likelihood of associated congenital hyper coagulable state or chronic myeloproliferative syndrome
What do you see and what is first treatment in PE?
Shortness of breath, chest pain
-Tx: first heparin, then may need vena cava filter/”strainer” if more traveling thrombi
With any DVT, what is it usually caused by?
Surgery/trauma/sepsis OR due to serious underlying congenital or acquired hyper coagulable state (e.g. malignancy)?
What is the #3 mechanism of atherosclerosis?
Aorta/large artery aneurysm or dissection due to arterial wall weakening
What is aneurysmal dilation?
- Especially affects aorta (Laplace’s law) but also can involve medium to large arteries
- Mechanism of weakening:
- -Ordinary atherosclerosis (esp. infra-renal abdominal aorta in smokers)
- Hypertension (esp. ascending throacic aorta)
- Misc. causes: inherited connective tissue disease (e.g. Marfan’s), vasculitis (Takayasu’s and giant cell - big vessel vasculitis), connective tissue/autoimmune diseases, and infection or aortic/arterial wall
- –> most feared complication: rupture and exsanguination
What is Aortic Dissection?
Dissecting hemorrhage/hematoma within aortic wall
- Type A (most lethal) = ascending +/- more distal aorta –> may lead to tamponade & coronary artery occlusion
- Type B = descending aorta and/or aortic arch
What are the pre-disposing factors for dissection?
- HTN if patient > 40 yrs
- Inherited connective tissue disorder (e.g. Marfan’s) if patient
What is the #4 mechanism of atherosclerosis, Vasculitis?
=inflammation of vascular wall ranging from neutrophilic to granulomatous
- lumen compromise secondary to inflammatory reaction +/- overlying thrombosis
- can be associated with secondary aneurysms
- Clinically a spectrum from benign skin limited disease (luekocytoclastic vasculitis) commonly to aggressive visceral vasculitis disease with high mortality (e.g. ANCA-associated vasculitides)
What age groups are vasculitic diseases/symptoms common?
- Largely adult diseases:
- -Except Henoch-Schonlein Purpura (HSP = IgA-related vasculitis) and Kawasaki disease (risk of coronary vasculitis)
- Vasculitis in middle-aged/elderly adults:
- if affecting distribution of external carotid artery = GIANT CELL (TEMPORAL) arteritis with risk of vision loss: diagnose with temporal artery biopsy and Rx with corticosteroids
What vasculitis might you see commonly in practice?
Giant cell arteritis: external carotid system is inflamed –> risk of vision loss
What are 5 life-threatening/aggressive vasculitis in adults?
- Anti-neutrophil cytoplasmic antibody (ANCA) - associated diseases (small vessel vasculitis)
- -Wegener’s: anti-PR3 antibodies (c-ANCA)
- -Microscopic polyangiitis: anti-myeloperoxidase Ab (MPO = pANCA) - Goodpasture’s syndrome = anti-glomerular basement membrane antibodies (anti-GBM)
- Occasionally connective tissue diseases (e.g. SLE)
- Polyarteritis nodosa (PAN)
- Churg-Strauss syndrome (asthma with partial association with anti-MPO)
What is on your differential if you see a vasculitis with pulmonary-renal syndrome?
- Diffuse pulmonary hemorrhage plus rapidly progressive glomerulonephritis
- -> Ddx: ANCA-associated vasculitis vs. Goodpasture’s vs. SLE
How to diagnose vasculitis using clinical suspicion?
Often challenging differential diagnosis exercise (variable/non-specific symptoms)
How to diagnose vasculitis using serological testing?
- Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) = systemic inflammation markers
- Antibody detection: ANCA (PR3/MPO), ANA/anti-ds DNA, anti-GMB, IgA detection in tissues with immunofluorescence
- Misc: cryoglobulins, complement (C3/C4), and Hepatitis B and C serology
What are routine things you order for vasculitis diagnosis?
ANCA panel + autoimmune panel!
What imaging studies do you use for vasculitis diagnosis?
Especially aorta (Takayasu's disease) and organ-directed angiography (small aneurysm formation in PAN: kidneys, mesentery) -Chest X-ray/CT scan (Wegener's/pulmonary-renal syndrome)
What tissue biopsies are used for vasculitis diagnosis?
Skin or deeper
-Especially ANCA-associated disease/pulmonary-renal syndromes (lung or kidney Bx), giant cell arteritis (temporal artery), HSP (kidney/skin), connective tissue disease with a dominant vasculitic component (varied site biopsies) and leukocytoclastic vasculitis (skin)
What are the rarest vasculitis categories?
-Polyarteritis nodosa
-Churg-Strauss syndrome
-Thromboangiitis obliterans
(Buerger’s disease) = distal extremity arteritis in heavy cigarette smokers
What are the benign types of vascular neoplasms?
- Hemangiomas
- Lymphangiomas
- Glomus tumor
- Bacillary angiomatosis
What is a Hemangioma?
Most common type of benign vascular neoplasm.
- Dominantly prefer the skin (cherry/purple papules)
- May involve any visceral organ: but favors liver, spleen and soft tissue
- Pyogenic granuloma - rapidly growing/friable capillary hemangioma in response to trauma - unpredictable response to trauma - not concerning
What are lymphangiomas?
Uncommon
-Largest examples most frequently in neck/axilla of young children (cystic hygroma)
What is a glomus tumor?
Glomus cell proliferation associated with vascular channels: PAINFUL small tumors of distal digits.
What is Bacillary angiomatosis?
Vascular proliferation associated with Bartonella infection (e.g. cat scratch species) in immunosuppressed patients
What are vascular ecstasies?
- Usually discrete lesions with dilated pre-existing vessels resembling hemangiomas but appearing flat/non-papular
- Very common in skin/mucous membranes
- Common cause of birth marks (e.g. port wine stain): extreme form = Sturge-Weber syndrome
- Systemic vascular ectasia syndrome with risk of serious bleeding (epistaxis, GI, GU) = Osler-Weber-Rendu (Hereditary Hemorrhagic Telangiectasia)
What are arteriovenous malformations?
- Tangled mass of arteries and veins without intervening capillary bed
- If large enough: can cause high output heart failure
- In brain: risk of rupture with fatal cerebral hemorrhage
What is an arteriovenous fistula?
Short circuiting of vascular system.
- From penetrating vascular injury
- Arterial aneurysm rupturing into adjacent vein
- Surgically created for hemodialysis
What are two malignant, LOW GRADE vascular proliferations?
- Kaposi’s sarcoma
2. Epithelioid hemangioendothelioma
What is Kaposi’s sarcoma?
SKIN +/- visceral involvement:
- Associated with HHV-8
- HIV and non-HIV associated types
- Immunosuppressed vs. non-immunosuppressed patients
- Very common in Africa
- Some older males have slow growing kaposi sarcoma on their lower legs
What is Epithelioid hemangioendothelioma?
Esp. liver and soft tissue
What is the most common HIGH GRADE malignant vascular neoplasia?
Angiosarcoma
What is Angiosarcoma?
- Tendency to occur in skin of head and neck in elderly but any visceral soft tissue site can be affected (e.g. liver, breast)
- Typically aggressive reddish/purple lesions in skin: often recurrent disease with hematogenous metastases.
- Patients with chronic lymphedema: Inc. risk of angiosarcoma (e.g. post mastectomy, radiation, ancillary dissection patients = Stewart-Treves Syndrome)
