Vascular Anomalies, HTN, Atherosclerosis, Aneurysms/Dissections Flashcards
3 concentric histologic layers of blood vessels
Intima (single layer of endothelial cells)
Media (well organized in arteries, haphazard in veins)
Adventitia (external to media, often separated from it by wide external elastic lamina)
Describe media component in elastic arteries
High elastin content — allows expansion during systole, recoil during diastole —> propels blood toward organs
What changes occur in the media component of elastic arteries with age?
Becomes less compliant with increasing age —> increased systolic BP
Describe media component in muscular arteries
Circumfirentially oriented smooth muscle; arteriolar smooth muscle contraction = vasoconstriction, or relaxation = vasodilation
______ are the principle point of physiologic resistance to blood flow — wherein resistance to fluid flow is inversely proportional to the fourth power of the diameter
Arterioles
[Small changes in vasoconstriction at this level has profound effects on BP]
Small arterioles that supply O2 to the outer media of large arteries
Vaso vasorum
Most inflammatory reactions affect what type of blood vessel?
Veins — leads to vascular leakage and leukocyte exudation
Describe architecture of veins
Larger lumens, thinner and less organized walls
Less rigid = susceptible to dilation and compresion, as well as infiltration by tumors and inflammatory processes
Reverse flow d/t gravity is prevented in the extremities by ____ ____
Venous valves
Describe architecture and function of lymphatic vessels
Thin walled, lined by specialized endothelium
Return intestinal fluid and inflammatory cells to the bloodstream
Transport bacteria etc. and tumor cells, making them a pathway for disease dissemination
Blood pressure control occurs at the level of the _______
Gas and nutrient exchange occur at the level of the _____
Arteriole
Capillary
ADPKD is associated with what type of vascular anomaly?
Berry aneurysm (circle of willis)
Anomaly characterized by abnormal connection between arteries and veins; in other words, capillaries are not present
Arteriovenous malformations (AVM)
Large or multiple AVMs may shunt blood from arterial to venous circulation, forcing the heart to pump additional volume leading to ______
High-output cardiac failure
Focal irregular thickening in medium and large musclar arteries, including renal, carotid, splanchnic, and/or vertebral vessels
Fibromuscular dysplasia
With fibromuscular dysplasia, first degree relatives have an increased incidence, as do young _____.
Medial and intimal hyperplasia leads to _____ _____
This condition displays on angiography as ___________-appearing due to marked attenuation of adjacent media
One of the major complications is development of an ______
Women
Luminal stenosis
“String of beads”
Aneurysm
Fibromuscular dysplasia of renal arteries leads to what complication?
Renovascular HTN
Cell type that creates nonthrombogenic surface, maintaining blood in fluid state and modulating the medial smooth muscle tone, metabolizing hormones (angiotensin), regulating inflammation, and affecting growth of other cell types (especially muscle cells)
Endothelial cells
[note that endothelial dysfunction results in proinflammatory and prothrombogenic state, resulting in thrombus formation, atherosclerosis, and vascular lesions of HTN]
Describe vascular smooth muscle cells
Ability to proliferate (can be maladaptive)
Synthesize collagen, elastin, and proteoglycans
Elaborate growth factors and cytokines
Vasoconstriction and/or dilation
Stereotypical response of a vessel wall to ANY insult
Intimal thickening
[associated with endothelial cell dysfunction or loss; stimualtes sm m cell recruitment and proliferation and associated matrix synthesis]
Neointimal sm m cells are motile, undergo cell division, and acquire new biosynthetic capabilities
T/F: smooth muscle cells can not return to nonproliferative state even if endothelial layer is normalized
False — these cells CAN return to nonproliferative state with normalization of endothelial layer (a change that may take place with lifestyle modifications, medication, etc.)
However, the healing response can result in intimal thickening that may impede blood flow
What is the initial event following vascular injury?
Endothelial cell activation!
Insults d/t turbulent flow, HTN, cytokines, complement, bacterial products, lipid products, hypoxia, acidosis, viruses, cig smoke, etc. —> increased expression of PROCOAGULANTS, ADHESION MOLECULES, and proinflammatory factors as well as altered expression of chemokines, cytokines, and GROWTH FACTORS signify “activated state”
Response to vascular injury:
- Recruitment of smooth muscle cells or smooth muscle precursor cells to the _____
- Smooth muscle cell _____
- Elaboration of ______
Intima
Mitosis
ECM (thrombogenic!)
Definition of hypertensive vascular disease as it relates to increased risk of atherosclerosis
Sustained systolic > 139 mmHg, or sustained diastolic >89 mmHg associated with increased risk of atherosclerosis
Causes of secondary HTN
Primary aldosteronism, Cushing syndrome, or pheochromocytoma
[other causes — renal disease, exogenous hormones, acromegaly, thyroid conditions, pregnancy, coarctation of aorta, polyarteritis nodosa, psychogenic, sleep apnea, acute stress, increased ICP]
HTN secondary to __________ is caused by increased production of renin from the ischemic kidney.
A _____ can be heard on auscultation of the affected kidneys
Renal artery stenosis
Bruit
What pt populations are at increased risk of essential (primary) HTN? What are some complications?
Risk factors: increasing age, African Americans have higher prevalence
Complications: cardiac hypertrophy and heart failure, multi-infarct dementia, renal failure
50% of untreated HTN pts die of ischemic heart disease (IHD) or CHF; another 1/3 die of stroke
Signs and symptoms of malignant HTN
Systolic > 200 mmHg, diastolic > 120 mmHg
Severe HTN, renal failure, retinal hemorrhages and exudates, +/- papilledema; often superimposed on pre-existing benign HTN
Untreated leads to death within 1-2 years
BP is a function of what 2 physiologic processes?
Cardiac output — HR and stroke volume (strong influence by blood volume — relationship with renal sodium excretion vs. reabsorption)
Peripheral vascular resistance — regulated at level of arterioles; influenced by neural and hormonal inputs
Humoral and neural factors that cause constriction in peripheral vessels
Humoral: Angiotensin II Catecholamines Thromboxane Leukotrienes Endothelin
Neural:
Alpha-adrenergic
Humoral and neural factors that cause dilation in peripheral vessels
Humoral:
Prostaglandins
Kinins
NO
Dilators:
Beta-adrenergic
The volume expansion resulting from activation of the RAAS induces myocardial release of ______, leading to Na+ excretion and diuresis as well as vasodilation - thus lowering BP
ANP
What condition in the kidney might result in RAAS activation and ANP release?
Renal artery stenosis
Compare/contrast the 2 forms of small blood vessel disease result from HTN
Hyaline arteriolosclerosis — homogenous pink (hyaline) thickening of the vessel wall, with associated luminal narrowing
Hyperplastic arteriolosclerosis — occurs in SEVERE HTN, smooth muscle cells form concentric lamellations (“onion skinning”) with resultant luminal narrowing
What condition tends to occur in those >50 y/o and is characterized by calcification of muscular arteries, involving internal elastic membrane, but there is NO narrowing of the lumen, and thus NO clinical significance?
Monckeberg medial sclerosis
Raised lesion with a soft grumous core of lipid covered by a fibrous cap
Atheroma = atheromatous = atherosclerotic plaque
[used interchangeably]
Why are premenopausal women somewhat protected from atherosclerosis?
Atheroprotective effects of estrogen
Major risk factor for atherosclerosis that is sufficient to initiate atheroma development even in the absence of other factors
Hypercholesterolemia
How does metabolic syndrome contribute to atherosclerosis risk?
Insulin resistance, HTN, dyslipidemia, hypercoagulability, and proinflammatory state may contribute to endothelial dysfunction and/or thrombosis
What serum marker may be used to predict cardiovascular risk?
C reactive protein (CRP)
Atherosclerosis does not occur randomly in vessels, nor does it occur everywhere uniformly. Where do most lesions tend to occur and why?
Most lesions tend to occur at opening of exiting vessels, branch points, posterior abdominal aorta, etc. — due to HEMODYNAMIC TURBULENCE and other flow disturbances in these locations
Lipids in atheromatous plaques are predominantly cholesterol and cholesterol esters; they accumulate in the _____, are taken up by macrophages and partially oxidized.
This modified LDL further accumulates in macrophages and ______ cells, forming _____ cells and a lesion known as a “fatty streak”. this stimulates an inflammatory response to accumulation of this toxic form of LDL
Intima
Smooth muscle; foam
As part of the pathogenesis of atherosclerosis, accumulatioin of cholesterol crystals within macrophages is recognized by the inflammasome, which leads to ____ secretion. More macrophages and ______ are recruited and activated. Inflammatory cytokines further activate endothelial cells, and growth factors stimulate smooth muscle cells to migrate to the intima and proliferate.
IL-1; T-lymphocytes
Several growth factors are implicated in smooth muscle proliferation. What are some examples?
PDGF (released by locally adherent platelets)
Fibroblast growth factor
TGF-alpha
Once there is initial formation of an atheromatous plaque, the soft fibrofatty structure becomes covered with a fibrous cap (dense collagen fibers). The center of the plaque is _______, containing lipid, debris, foam cells, and thrombus, surrounded by a zone of inflammatory and smooth muscle cells
Necrotic
Common sites of atherosclerosis involvement
[in decreasing order of frequency]:
Abdominal aorta Coronary arteries Popliteal arteries Internal carotid arteries Circle of willis
Complications of atherosclerotic plaques
Rupture and ulceration — may lead to thrombosis
Hemorrhage — may follow plaque rupture
Embolism — may follow plaque rupture
Aneurysm formation
One of the consequences of atherosclerosis is gradual shrinkage of vessel lumen, eventually leading to ischemia downstream. At a point known as _____ _____, approximately 70% of the vessel is occluded which may lead to chronic ischemia of myocardium, bowel, brain, the extremities, etc.
Critical stenosis
What are some characteristics of atheromatous plaques that are more prone to rupture?
Those in which the fibrous cap is continually being remodeled
Those with increased inflammation — which can accelerate cap degradation and inhibit its resynthesis, thus reducing the amount of collagen in the cap and weakening it
Physical stresses can cause plaque rupture — like changes in BP, vasoconstriction, etc.
T/F: there is a direct relationship between plaque thickness and likelihood of rupture
True — the thicker the plaque, the more vulnerable it is to rupture
What is the difference between true vs. false aneurysm?
True aneurysm = an intact (but thinned) muscular wall at the site of dilation
False aneurysm = defect through the wall of the vessel, communicating with an extravascular hematoma
What connective tissue disorder is associated with increased risk of aneurysm formation?
Marfan syndrome — defective fibrillin synthesis
Conditions in which there is net degradation of vascular wall CT can predispose pts to aneurysms, this includes inflammatory conditions like atherosclerosis, which result in increased ________
Matrix metalloprotease
What are some conditions that predispose to aneurysm by weakening the vascular wall by ischemia?
Atherosclerosis —> ischemia of inner media
HTN —> ischemia of outer media
Tertiary syphilis —> ischemia of outer media (thoracic aorta)
How does tertiary syphilis contribute to ischemia of the outer media (particularly in thoracic aorta)
Obliterative endarteritis (characteristic of late-stage syphilis) shows a predilection for small vessels, including those of the vasa vasorum of the thoracic aorta
This leads to ischemic injury of the aortic media and aneurysmal dilation which sometimes involves the aortic valve annulus (aortic valve regurgitation) — sometimes referred to as “tree barking”
During pathogenesis of aneurysms, loss of vascular wall elastic tissue, or ineffective elastin synthesis leads to cystic medial degeneration, with disrupted and disorganized elastin filaments and increased ground substance (proteoglycans). Cystic medial degeneration is a final common result of different conditions, including ischemic medial damage and _____ syndrome.
However, the 2 MOST IMPORTANT causes of aortic aneurysms are ______ and ______
Marfan
Atherosclerosis; HTN
Where do mycotic aneurysms originate from? (multiple)
Septic emboli (usually complication of infective endocarditis)
Extension of an adjacent suppurative process
Circulating organisms directly infecting the arterial wall
AAAs are characterized by severe _______ of the aorta, covered with mural thrombus. They may be detected as a _________ mass in the abdomen
Atherosclerosis; pulsating
AAAs occur in the abdominal aorta, usually below the _____ arteries and often involve the _______ arteries
Renal; common iliac
Complications of AAA
Rupture and hemorrhage
Occlusion of branching arteries and downstream ischemia
Embolism
Impingement on another structure
AAA rupture risk is related to aneurysm ______
Size! — aneurysms 5cm or greater are usually managed surgically
Thoracic aortic aneurysms are often d/t _____, or less commonly congenital defects in CT: Marfan syndrome. Marfan is a _____ inherited disorder resulting in defective synthesis of fibrillin (FBN1), leading to aberrant ______ activity that weakens elastic tissue
HTN
AD
TGF-B
Clinical presentation of thoracic aortic aneurysm
Clinical presentation is often d/t impingement of: lower respiratory tree, esophagus, recurrent laryngeal nn
Aortic valvular insufficiency
Rupture
Complication of aortic aneurysm in which blood enters a defect in the intima and travels through a tissue plane within layers of the aortic media
Who is most at risk for this complication?
Aortic Dissection
Most commonly occurs in hypertensive males age 40-60, or younger patients with Marfans
[primary risk factor is HTN]
Classic presentation of aortic dissection
Sudden onset of severe chest pain (usually beginning in anterior chest), radiating to the back between the scapulae, and moving downward as the dissection progresses
—can be confused with AMI!
What is a “double-barreled aorta”?
If dissecting aorta hematoma re-enters the lumen of the aorta through a second distal intimal tear, a new false vascular channel is created — creating appearance of double-barreled aorta
This averts a fatal extraaortic hemorrhage, and over time, such false channels can be endothelialized to become recognizable chronic dissections
With aortic dissection, blood enters aortic wall via an intimal tear (cause is generally unknown), forming an intramural hematoma. Usually in hypertensive patients, there is some degree of cystic medial degeneration. Where do most aortic dissections arise?
Most arise in the ascending aorta, within 10 cm of the aortic valve
Aortic dissections can rupture through the _______ leading to massive hemorrhage or _____ ______ (hemorrhage into pericardial sac)
Adventitia; cardiac tamponade
Classifications of aortic dissections and which are more common
Type A = DeBakey I and Debakey II
Type B = DeBakey III
Type A dissections (involving the ascending aorta) are more common and associated wtih higher morbidity and mortality. They are treated with antihypertensive therapy and an attempt to surgically repair the intimal tear
