Vascular Path Flashcards
causes of 2* HTN
any cardio, renal, and endocrine dx
=inc cardiac output +inc vasoconstriction= inc BP
a. Renal disease:polycystic disease, renal cell carcinoma (RCC), chronic renal failure, glomerulonephritis, renal artery
stenosis and fibromuscular dysplasia
b. Adrenocortical hyperfunction:congenital adrenal hyperplasia, adrenal tumors
c. Adrenal medullary hyperfunction: pheochromocytoma
d. Thyroid dysfunction: myxedema)
e. Pituitary dysfunction: acromegaly
f. Cardiovascular disease: coarctation of the aorta, polyarteritis nodosa
g. Pregnancy: eclampsia and pre-eclampsia
h. Neurologic disease:↑ intracranial pressure
i. Medications and drugs: glucocorticoids, cyclosporine, sympathomimetics, cocaine
describe hypertnsion (HTN)
sustained BP >139 systolic or > 89 diastolic
M>F, Afro-Am, smokers, obesity
90% primary (essential HTN/ unknown cause- linked to calories, salt or alcohol)
10% secondary (adrenal/renal cause)
HTN: increased risk for
eye (blindness), heart (LVH, IHD/MI, CHF, aortic dissection),
renal (ESRD), & brain (stroke)
INCREASE RISK OF ATHEROSCLEROSIS
(2) hitso pathologic features of HTN
Hyaline arteriolosclerosis- protein leaks
hyperplastic arteriolosclerosis- onion-skin
INCREASE RISK OF ATHEROSCLEROSIS
describe iodiopathic/primary/essential HTN
genetic + environmental causes ( linked to calories, salt or alcohol)
90% HTN cases
defects in renal homeostasis + vasoconstriction + defects in smooth muscle= inc cardiac output and inc peripheral resistance= HTN
(4) hormones maintaining BP homeostasis
renin- renal (increases BP)
angiotensinogen- hepatic (increases BP)
aldosterone- adrenal (increases BP)
ANP- cardiac (decreases BP)
Aortic Dissection: types
bad= proximal aorta=risk of rupture into the pericardial sac with cardiac tamponade and harm to coronary or cerebral vessels Type A (DI/DII): med/surgical emergency (poor prognosis); Type B (DIII): distal dissections= better prognosis
high risk for aortic dissection
- Connective tissue diseases (Marfan, Ehlers-Danlos= cystic medial degeneration)
- hypertension (Hypertrophy of the vasa vasorum)
- complication of arterial cannulation ( loss of smooth muscle)
- pregnancy
Aortic Dissection
Intimal tear, dissection into media (middle/outer third), thru adventitia HMG into chest, abdominal, or pericardial sac (poor prognosis); false channel (better prognosis)
Hyaline Arteriolosclerosis
Hyaline protein deposits, narrowed endothelial cell damage: DM, HTN (decades), elderly • endothelial cell dysfunction: plasma protein leakage/inc. SM cell & ECM synthesis • a/w Nephrosclerosis Renal Failure
Hyperplastic Arteriolosclerosis
Laminated “onion-skin” lesions
smooth muscle proliferation) obliterates lumen
Causes: fibrinoid nectosis, “flea bitten” kidney
• Life-threatening organ damage: brain, kidneys, heart medical emergency
Atherosclerosis
Affects elastic and muscular arteries
• Progressive accumulation of
lipid/lipid debris, smooth muscle cells, extracellular matrix, T-lymphocytes, macrophages/foam
cells in the intima
• Encroaches on the media &
adventitia (Atheroma) narrowing of the lumen (e.g., IHD, thrombus)
chronic inflammation
Atherosclerosis: modifiable risk factors
-Hypercholesterolemia(HC)/ Hyperlipidemia(HL) (Most important cause)
– HTN (major risk factor)
– DM (inc. HC/HL)
– Cigarette Smoking (inc. CRP)
steps in Pathogenesis of Atherosclerosis
- endothelial cell injury/dysfunction
- increase permeablility
- cytokine release and leukocyte/monocyte/macrophage emigration
- smooth muscle proliferation
- engulf lipid
- fatty streak
- ECM deposition
- fibrofatty atheroma
- plaque
- intimal ischemia
Elevated serum levels of CRP
Inflammation marker Risk Factor: - Atherosclerosis - Acute Myocardial Infarction - Stroke - Peripheral arterial disease - Sudden cardiac death
Atheromas: Thick vs Thin Fibrous Cap
Thin Fibrous Cap: Increase Risk of
Acute Coronary Thrombosis (AMI)
saccular aneurysms
- Saccular- spherical outpouchings
fusiform aneurysms
- Fusiform- diffuse, long, circumferential dilation
What are the two most important causes of aortic aneurysms?
HTN+atherosclerosis
other Risk: CT dx: Marfan (fibrillin), Scurvy, Ehler-Danlos; Matrix Metalloprotease (MMP)
What are the two most common locations for aortic aneurysms?
Below the renal arteries and above the bifurcation of the aorta. They may be fusiform or saccular, up to 15 cm in diameter and up to 25 cm in length. They are often accompanied by smaller aneurysms of the iliac arteries.
describe inflammatory aneurysms
Fibrosis; lymphocytes, marcophages, giant cells
Microbes infect plaque
describe mycotic aneurysms
invades Vasa vasorum= ischemia
Obliterative endarteritis
endarteritis
inflammation of the inner lining of an artery
Obliterative endarteritis
Obliterative endarteritis- severe proliferating inflammation of the inner lining of an arterythat results in an occlusion of the lumen of the artery
Dissections:
Intimal tear within the wall of a blood vessel, which allows blood to separate the wall layers
Massive hemorrhage
Aortic dissection: Types A/B
Type A: Debakey 1- ascending + descending aorta
Type A: Debakey 2- ascending aorta
Type B: Debakey 3- descending aorta
(*worst= closest to aortic valve)
Non-infectious Vasculitis:
Inflammation of vessel walls Thick, nodular Distrupts elastic lamina 1) Positive for immune complex deposition, 2) Antineutrophil cytoplasmic antibodies (ANCA), 3) Antiendothelial cell antibodiess
what Non-infectious Vasculitis
affect Large vessels: aorta, extremities, head, neck (2)
Giant cell (temporal) arteritis Takayasu arteritis
what Non-infectious Vasculitis affect Medium vessels: visceral (2)
Polyarteritis nodosa
Kawasaki disease
what Non-infectious Vasculitis affect Small vessels: arterioles, venules capillaries (4)
Microscopic polyangiitis
Wegner granulomatosis
Churg-Strauss syndrome
Henoch-Schonlein Purpura
what Non-infectious Vasculitis affect Small/med a, extremity veins, nerves (1)
Thromboangiitis obliterans (Buerger disease)
what Non-infectious Vasculitis: Segmental, thrombosing inflammation of small and medium sized arteries, esp. the tibial and radial arteries
Thromboangiitis obliterans (buerger disease)
what Non-infectious Vasculitis: Systemic vasculitis of small and med sized arteries, esp the renal and visceral vessels, spares pulmonary vessels
Polyarteritis nodosa
what Non-infectious Vasculitis: Necrotizing or granulomatous vasculitis of small to medium vessels, esp. in the lungs and upper airway
Wegner granulomatosis
what Non-infectious Vasculitis: Granulomatous vasculitis of medium and large arteries with ocular problems and weakening of the pulses in the upper extremities (2)
Takayasu arteritis (female50yo)
what Non-infectious Vasculitis: Arteritis of large to medium vessels, predilection for coronary arteries
Kasasaki disease
what Non-infectious Vasculitis: Small vessel vasculitis mediated by IgA immune complexes
Henoch Schonlein purpura
what Non-infectious Vasculitis: Necrotizing vasculitis of capillaries, arterioles and venules
Microscopic polyangiitis
describe Giant cell (temporal) arteritis
Large vessels: aorta, extremities, head, neck
Granulomatous inflamm.
Intimal fibrosis
Tcells, multinucl. Giant cells
Temporal artery
Ophthalmic artery
>50yo
Polymyalgia rheumatica
describe Takayasu arteritis
Large vessels: aorta, extremities, head, neck
Granulomatous inflamm.
Reduced BP, weak pulse
<50yo
Aorta arch (transmural)
Japanese women
describe Polyarteritis nodosa
Medium vessels: visceral
Necrotizing inflamm
Histo: Fibrinoid necrosis, lesions at varying stages, “string of pearls” healing
Multiple organs
Renal arteries, mesenteric, spares pulmonary vessels
Chronic HBV
describe Kawasaki disease
Medium vessels: visceral
Arteritis, mucocutaneous lymph node sx
Erythema/Desquamative rash (Conjunctiva, oral cavity, Hands/feet)
Tx: Aspirin and gamma globulin
Causes: coronary artery aneurysm, heart/lung block
Histo: inflammatory cell infiltrates
Asian children
Coronary artery
Microscopic polyangiitis
Small vessels: arterioles, venules capillaries
Necrotizing vasculitis, p-ANCAs (MPO-ANCA)
Histo: All lesions are of same age; Fragmented, apoptotic neut
Tx: Immunosuppression
glomerulonephritis and pulmonary capillaries
Wegner granulomatosis
Small vessels: arterioles, venules capillaries
Granulomatous inflamm., Necrotizing vasculitis,
c-ANCAs
Respiratory tract (lungs+nasal+pharynx), glomerulonephritis
Churg-Strauss syndrome
Small vessels: arterioles, venules capillaries
Eosinophil-rich,
Granulomatous inflamm., Necrotizing vasculitis
p-ANCAs
Respiratory tract
Asthma
Blood eosinophil
Henoch-Schonlein Purpura
Small vessels: arterioles, venules capillaries
IgA immune complex deposition
Palpable purpura, hematuria
Children, follows URI
Thromboangiitis obliterans (Buerger disease)
Small/med a, extremity veins, nerves
Segmental, thrombosing inflamm., fibrous tissue,
Leads to vascular insufficency
Histo: Occluding thrombus & microabscesses
Ulceration & gangrene
Autoamputation of digits
Cigarettes
Arteries in extremities
(UE/radial; LE tibial)
digits
Infectious vasculitis
1) Bacterial
(pseudomonas),
2) Fungal (mucor;
aspergillus)
by vascular/hemato spread
Raynaud phenomenon
recurrent vasospasm of the fingers and toes and usually occurs in response to stress or cold exposure
reduced blood= white/blue
Hemangioma
benign vascular tumor
vessels filled with blood
3 types (capillary, cavernous, pyogenic)
Histo: organized, lobular architecture. Each lobule consists of small vessels
Bacillary angiomatosis (bartonella)
benign
vascular proliferation involving the skin, bone, brain, and other organs
Gross: Red papules or nodules
Histo: PMN inflammation & capillary proliferation
-gram negative bacilli Bartonella on Warthin-Starry stain
Risk: immunocompromised patients,
also causes: cat-scratch fever & trench fever
-Tx w/ Abx’s
Kaposi sarcoma
Intermediate grade malignant tumors:
Locally invasive
Risk: AIDS (herpesvirus type 8), east. European males, transplants
Gross: - Red-purple patches, macules, papules, plaques or nodules
Morph: - nodular, Sheets of plump, proliferating spindle cells
Dilated irregular endothelial cell-lined vascular spaces with interspersed lymphocytes, plasma cells, and macrophages
Tx: excision,radiation,chemo Rx (good prognosis)
Angiosarcoma
malignant: aggressive tumor
Proliferation of endothelial cells (cell marker CD31)
breast, skin, liver
Gross: Aggressive, poorly demarcated, variegated, fleshy masses
Histo: dense clumps of Atypical cells lining vascular lumen
Risk: older adults, PVC, arsenic
(5 yr survival= 30%)
Syphilitic Aneurysm
Untreated 3* syphilis, treponema pallidum
Histo: “tree bark” intima
Enlarged heart
Causes thoracic aortic aneurysm
Obliterative endarteritis of vasa vasorum
HOW IS VASCULITIS DIAGNOSED?
Biopsy—surgical removal of a small piece of tissue for inspection under a microscope Angiography—a type of X-ray to look for abnormalities of blood vessels Blood tests (+ANCA)
effects of Antineutrophil cytoplasmic antibodies (ANCA):
Leads to vascular injury
Autoantibodies cause autoimmune swelling and inflammation of blood vessels
C-ANCA (anti-proteinase-3/PR3-ANCA)
Attacks in cytoplasm
Neutrophil azurophillic granules
Increase PMN activity
Intracellular components
Microbial peptides (polyangiitis)
P-ANCA (anti-myeloperoxidase/MPO-ANCA)
Attacks near nucleus
Lysosomal granules
Forms Oxygen free radials
Microbial antigens
Infection
Endotoxins
autoantibodies
Proliferative restenosis
Proliferative restenosis- metabolic syndrome = inc risk for coronary atherosclerosis
Tx: angioplasty: place stent with paclitaxel to limit smooth muscle hyperplasia
Risk factors for atherosclerosis in pulmonary vasculature: (different than systemic risk factors)
emphysema and fibrosis (obstructive and restrictive dx’s)
Raynaud phenomenon
recurrent vasospasm of the fingers and toes and usually occurs in response to stress or cold exposure
reduced blood= white/blue
varices
abnormally dilated vessel with a tortuous path
Caused by blocked venous drainage
phlebothrombosis vs Thrombophlebitis
phlebothrombosis= blood clot in a vein without inflammation. Thrombophlebitis = inflammation of a vein with a clot
Lymphangitis
inflammation or an infection of the lymphatic channels that occurs as a result of infection at a site distal to the channel.
Caused by acute streptococcal infection of the skin
lymphedema
lymphatic obstruction
localized fluid retention and tissue swelling caused by a compromised lymphatic system
Develops over time
Causes: infection, cellulitis
define angiitis & vasculitis
inflammation of blood vessel walls
Thick, nodular
Disrupts elastic lamina
What are the complications of hypertension?
Heart – concentric LV hypertrophy → LV dilatation → congestive heart failure, arrhythmias
• Blood vessels – arteriosclerosis → myocardial infarction, peripheral vascular disease, Aortic dissection
• Kidneys – ↓ GFR → chronic renal failure
• Brain – stroke (due to atherosclerosis) and intracerebral hemorrhage (due to Charcot-Bouchard microaneurysms)
• Retina - retinopathy → blindness
What are the risk factors for atherosclerotic cardiovascular disease?
Age, Sex (Male), Family history and genetic abnormalities, Post-menopausal females (decreased estrogen)
Hyperlipidemia, Hypertension, Diabetes
Smoking, Obesity, Inactivity, Stress, Alcohol
Genetic: rare single gene defects of aldosterone or Na+ channels. Polymorphisms at multiple sites are much more common,
but not well defined.
“Response to Injury” Hypothesis: pathogenesis of atherosclerosis
atherosclerosis is an aberrant chronic inflammatory response:
All five cell types in an atherosclerotic plaque are capable of liberating mediators that have a role in the disease progression.
These interact with the ECM and induce the formation of the thick fibrous cap with the lipid core.
What are complications of atherosclerotic disease?
myocardial infarction/ischemic heart disease, strokes, aortic aneurysms, and peripheral
vascular disease (distal lower extremity gangrene). In addition, rupture of an atherosclerotic plaque may cause thrombus
formation and occlusion of a vessel.
Which inflammatory marker in the serum correlates with the risk of ischemic heart disease and is important in the
overall risk stratification of patients?
Serum C-reactive protein (CRP)
What population is most at risk for the development of an abdominal aortic aneurysm?
Male, smokers, > 50 years of age, atherosclerosis, HTN
What is the incidence of abdominal aortic aneurysms?
<5% in males over 60 even with close to 100% aortic atherosclerosis in that population
What determines the risk of rupture of an abdominal aortic aneurysm?
The risk of rupture is directly related to the size of the aneurysm.
negligible risk if < 4cm,
1% per year if between 4-5cm,
11% per year if between 5-6 cm,
and 25% per year if > 6 cm.
Surgical treatment (prosthetic grafts) are usually recommended if the AAA is 5cm or greater in diameter
What is the mortality of abdominal aortic aneurysm surgery with and without rupture?
Operative mortality for un-ruptured aneurysms is approximately 5% and emergency surgery after rupture has a mortality rate
>50%
What is the mortality of a ruptured abdominal aortic aneurysm?
Mortality is about 50% for emergency surgery to repair a ruptured AAA, whereas it is only 5% operative mortality for
unruptured AAA
Describe the clinical features (sx) of temporal arteritis?
fever, fatigue, weight loss; facial pain and headache, especially along the course of
the superficial temporal artery, which is often painful to palpation. Ocular symptoms, associated with involvement of the ophthalmic artery, appear abruptly in 50% of patients, and include diplopia to complete vision loss.
What are (3) TYPES OF Hemangiomas (common benign vascular tumors) and what are their histologic features?
- Capillary hemangiomas of of skin, subcutaneous tissues, mucosa, liver, spleen or kidneys, which are un-encapsulated
aggregates of closely packed thin walled capillaries. These lesions frequently regress spontaneously to variable
degrees. - Cavernous hemangiomas with infiltrative growth of large, dilated vascular channels into deeper structures; they do
not tend to regress. and - Pyogenic granulomas which are pedunculated skin nodules of proliferating capillaries with extensive edema and
inflammation.
What are the diagnostic criteria of Kawasaki disease
- Bilateral non-exudativet conjunctival injection
- Changes of the mucosa of the oropharynx, including infected pharynx, infected and/or dry fissured lips, strawberry tongue
- Changes of the peripheral extremities, such as edema and/or erythema of the hands or feet, desquamation, usually
beginning periungually - Rash, primarily truncal, polymorphous but nonvesicular
- Cervical adenopathy
