Blood Vessels Flashcards
1
Q
Regional specializations of the vasculature
A
aorta: elastic tissue to accommodate high pulsatile forces, with the capacity to recoil and transmit energy into forward blood flow.
muscular arteries and arterioles: concentric rings of medial smooth muscle cells whose contractile state regulates vessel caliber and, thereby, blood flow and blood pressure.
venous system: relatively poorly developed medial layers that permit greater capacitance.
capillary wall: permits ready diffusion of oxygen and nutrients because it is comprised only of an endothelial cell and sparse encircling pericytes.
Thus, loss of aortic elastic tissue in a large artery may result in aneurysm, while stasis in a dilated venous bed may produce a thrombus.
2
Q
Arteries
A
Large or elastic:
aorta, its large branches and pulmonary arteries
Medium-sized or muscular
other branches of the aorta
Small: less than 2 mm in diameter vasa vasorum feed medium and large arteries outer 1/2 to 2/3 of the media
3
Q
Arterioles
A
20 - 100 μm diameter
Within the substance of tissues and organs
Arterioles (and small muscular arteries) are primary regulators of arterial blood pressure (autonomic system and other local and systemic controls)
Medial smooth muscle contraction changes lumen diameter
Resistance to fluid flow is inversely proportional to the fourth power of the diameter/radius
(i.e., halving the diameter/radius increases resistance 16-fold)
4
Q
Veins
A
Venous valves in the extremities
Large lumen
Approximately 2/3 of all the blood is in veins
Thin less well organized walls
***Postcapillary venules
Site of leukocyte exudation and vascular leakage
5
Q
Walls vs lumen in arteries and veins
A
Because it must sustain higher pressures, the artery has a thicker wall with more-organized elastin architecture than in the corresponding vein. Conversely, the vein has a larger lumen with diffusely distributed elastin, permitting greater capacitance.
6
Q
Capillaries
A
Approximately the diameter of a red blood cell (7-8 μm) or larger
Endothelial cell lining (no media)
Surrounding pericytes
Rapid exchange of diffusible substances
7
Q
Lymphatics
A
Endothelial cell lining (no media)
Valves in larger lymphatic vessels
System for returning interstitial tissue fluid and inflammatory cells to blood
Important pathway for disease dissemination
8
Q
Endothelial cells contain what important structure?
what types exist?
A
Contain Weibel-Palade bodies [membrane-bound storage organelles that contain von Willebrand factor (vWF)]
Junctions normally impermeable to large molecules (proteins) with exceptions:
- Fenestrated endothelial cells
- Discontinuous (sinusoidal)
endothelium
9
Q
Vascular Smooth Muscle- regulated by?
A
Responsible for vasoconstriction and dilation
Regulated by:
* promoters (PDGF, endothelin-1, thrombin, FGF, IFN-γ, and IL-1)
* inhibitors (heparan sulfates, NO and TGF-β)
* renin-angiotensin system, catecholamines, estrogen, and osteopontin (part of extracellular matrix)
Migrate to the intima and proliferate following injury
Synthesize collagen, elastin, and proteoglycans
Elaborate growth factors and cytokines
10
Q
Developmental (congenital, berry) aneurysms
A
saccular type aneurysm arising in an artery
with a developmental wall abnormality
seen in 2% of autopsies
mostly found in circle of Willis
11
Q
Arteriovenous fistulas
A
rare abnormal communications between arteries and veins
most congenital; some produced (rupture of an arterial aneurysm into adjacent vein, injuries that pierce walls of artery and vein, or inflammatory necrosis of adjacent vessels)
short-circuit blood and cause heart to pump additional volume (high-output cardiac failure can ensue)
12
Q
vascular anomalies that can rupture
A
developmental aneurysms (congenital, berry) and arteriovenous fistulas
13
Q
Fibromuscular dysplasia
A
focal irregular medial and intimal hyperplasia with thickening of walls of medium and large muscular arteries
occurs more commonly in young women
can cause HTN (affecting renal artery, –> compensatory renin)
14
Q
Hypertension (HTN)
A
Hypertension = Sustained chronically elevated pressure
Systolic > 140 mm Hg
2014 Evidence Based Guidelines suggest > 150/90 mm Hg for those > 60 years.
Diastolic > 90 mm Hg
Prehypertension
Systolic 120-139 mm Hg
Diastolic 80-89 mm Hg
29% of persons in the general population are HYPERTENSIVE
Risk for coronary artery disease, cerebral vascular accidents, hypertensive heart disease, aortic dissection, renal failure, etc
Systolic blood pressure is more important than diastolic blood pressure as a determinant of cardiovascular risk
15
Q
Blood Pressure Regulation
A
Blood pressure is proportional to cardiac output and peripheral vascular resistance
Major factors that determine blood pressure
Age, gender, body mass index, and diet (principally sodium intake)
Genetic variation in genes of renin-angiotensin-aldosterone system
Essential hypertension probably initiated by increased sodium retention with later coexisting increased vascular resistance
16
Q
Essential hypertension means
A
secondary
17
Q
Benign (essential) hypertension
A
controlled hypertension with no short term problems
18
Q
Hypertensive urgency
A
systolic >220 mm Hg or diastolic >120 mm Hg with no evidence of target organ damage
19
Q
Hypertensive emergencies
A
Accelerated hypertension- significant increase in B. P. associated with target organ damage (flame-shaped hemorrhages or exudates of fundus, renal failure, headache, angina, etc.)
Malignant hypertension- papilledema +/- accelerated HTN symptoms
20
Q
licorice ingestion
A
can cause hypertension
21
Q
3 patterns of arteriosclerosis
A
Arteriolosclerosis in small arteries and arterioles
Atherosclerosis (atheromas=atheromatous plaques=fibrofatty plaques) develops primarily in elastic arteries and muscular arteries
Monckeberg medial calcific sclerosis in muscular arteries of >50 y. o. with no vessel lumen narrowing (can ossify)
22
Q
Arteriolosclerosis (2 types)
A
1. Hyaline arteriolosclerosis Protein deposition (hyalinized) Seen in aging diabetes mellitus benign nephrosclerosis (hypertension)
- Hyperplastic arteriolosclerosis
Cell death (onion-skinning)
+/-necrotizing arteriolitis
Seen in malignant hypertension
23
Q
Atherosclerosis- levels of prevention
A
50% of deaths and serious morbidity in the Western World
ischemic heart disease mortality in US 5X Japan
1ry prevention – prevent the onset of disease (susceptible)
cigarette smoking, dietary habits, statins, and HTN control
2ry prevention – early diagnosis/risk factor assessment (asymptomatic)
3ry prevention – prevent recurrences with disease (symptomatic)
aspirin, statins, beta blockers, surgery
Improved treatments keeping patients alive
24
Q
Atherosclerotic Plaques
A
Can disrupt and precipitate thrombi or grow to cause decreased flow (obstruction)
→myocardial infarction, cerebral infarction, aortic aneurysms, peripheral vascular disease (gangrene), mesenteric occlusion, sudden cardiac death, chronic ischemic heart disease, and ischemic encephalopathy
Vasoconstriction can compromise lumen and disrupt plaque
Thrombus in/on plaque can eventually be incorporated into plaque
Can shed emboli
→focal and regional ischemia (TIAs, microinfarcts, ischemic digits)
Can encroach on media and weaken the vessel wall
→aneurysms and ruptures
** Turbulent flow and low shear stress →areas prone to atherosclerosis
Turbulent flow causes endothelial trauma and dysfunction
Laminar flow induces endothelial genes for products that protect against atherosclerosis (superoxide dismutase)
25
Where is atherosclerosis associated?
the intima
26
three outcomes of atherosclerotic plaques
aneurysm and rupture
occlusion by thrombus
critical stenosis
27
Obesity
Definition: “an accumulation of adipose tissue that is of sufficient magnitude to impair health”
28
Body mass index (BMI)
(weight in kilograms)/(height in meters)2
29
risks of obesity
diabetes, hypertension, hypertriglyceridemia, and low HDL cholesterol
Also increased risk of
nonalcoholic steatohepatitis, cholelithiasis, hypoventilation (Pickwickian) syndrome, hypersomnolence, secondary polycythemia, osteoarthritis, and cancers [endometrial and breast (hyperestrogenemia), thyroid, colon, kidney, gallbladder and esophageal (adenocarcinoma)]
30
Metabolic syndrome:
Obesity, dyslipidemia, hypertension, and insulin resistance (can also have hypercoagulability and inflammatory state)
Predisposes to cardiovascular disease and type 2 diabetes
31
Cholesterol Metabolism (breakdown)
2/3 LDL receptor pathway
1/3 Scavenger receptor pathway (oxidized LDL)!!!!
32
LDL receptor pathway of cholesterol metabolism
75% of LDL receptors are located on hepatocytes
The LDL receptor binds to apolipoproteins B-100 and E on LDL & IDL
→Endocytotic internalization
→↑Cytoplasmic cholesterol
→ Inhibition of cholesterol synthesis
Inhibit 3-hydroxy-3-methylglutaryl (3-HMG) coenzyme A reductase
Rate-limiting enzyme in the synthetic pathway
Statins also inhibit HMG-CoA reductase
Activate acyl-CoA: cholesterol acyltransferase (ACAT)
Favors esterification and storage of excess cholesterol
Down-regulates the synthesis of cell surface LDL receptors
Protects cells from excessive accumulation of cholesterol)
Statins promote synthesis of LDL receptors (↓intracellular cholesterol allows ↑LDL receptor formation )
33
Statins
block HMG CoA reductase →↓cholesterol levels and ↓cholesterol allows ↑LDL receptor formation
34
Hyperlipidemia
Mostly hypercholesterolemia
↑ risk with ↑ low density lipoprotein (LDL) LDL–C ≥190 mg/dL
↓ risk with ↑high density lipoprotein (HDL)
Exercise and alcohol ↑ HDL
Obesity and smoking ↓ HDL
↑LDL, ↓ HDL and ↑Lp(a) associated with ↑ atherosclerosis
Lowering cholesterol by diet or drugs slows atherosclerosis
Omega-3 beneficial
Trans-unsaturated fats are bad
Estrogens ↑ HDL &↓ LDL
Replacement therapy does not decrease risk for heart attacks in post menopausal women
↑ risk (2X) of coronary artery disease with oral contraceptive use in women >35 years who also smoke
35
Familial Hypercholesterolemia
Mutations in the LDL receptor gene
Toxic oxygen species from mФs and endothelium cause oxidation of LDL
Oxidized LDL receptors take over (scavenger receptor pathway)
LDL receptor mutations: > 900 of them
```
These mutations disrupt the receptor's
synthesis in the endoplasmic reticulum
***transport to the Golgi complex*
binding of apoprotein ligands
clustering in coated pits
recycling in endosomes
```
Class II (most prevalent); receptor protein transport from the endoplasmic reticulum to the Golgi apparatus is impaired due to abnormal protein folding
36
Familial HypercholesterolemiaGenetics and Phenotype
Autosomal dominant
Heterozygotes 2-3x elevation of plasma cholesterol levels
Homozygotes 5x elevation of plasma cholesterol levels
Develop severe atherosclerosis, mitral valve stenosis, corneal arcus and xanthomas
Die from complications as children or young adults
37
Other Atherosclerosis Risk Factors
elevated homocysteine
presence of lipoprotein a
elevated plasminogen activator inhibitor 1
Infections may contribute-- chlamydia pneumonia, ,herpes, cytomegalovirus
sedentary lifestyle
stress
38
C-Reactive Protein
Acute-phase reactant synthesized primarily by the liver
Has roles in opsonizing bacteria and activating complement
Involved in endothelial adhesion of WBCs and thrombosis
Strongly and independently predicts the risk of myocardial infarction, stroke, peripheral arterial disease, and sudden cardiac death
No evidence that lowering CRP reduces cardiovascular risk,
Smoking cessation, weight loss, statins and exercise all reduce CRP
39
Pathogenesis of atherosclerosis
Chronic endothelial injury (dysfunction)
Accumulation of lipoproteins (mainly LDL) with subsequent oxidation
Adhesion of monocytes with migration into the intima (now macrophages)
Adhesion and activation of platelets
Migration of smooth muscle cells becoming neointimal smooth muscle cells (proliferate and deposit extracellular matrix/collagen)
Accumulation of lipids in macrophages (foam cells), smooth muscle cells and extracellular spaces
40
Aneurysms
Localized abnormal dilation of a blood vessel or the wall of the heart
41
Most important causes of aortic aneurysms are
Atherosclerosis with associated inflammation (abdominal aorta)
macrophage metalloproteinases and inflammation induced smooth muscle apoptosis weaken vessel wall
Hypertension via ischemic medial cystic degeneration (thoracic aorta)
Other causes: Marfan syndrome (fibrillin), Loeys-Dietz syndrome (TGF-β receptors), Ehlers-Danlos syndrome (type III collagen), scurvy (collagen x-linking), trauma (traumatic aneurysms or arteriovenous aneurysms), congenital defects (berry aneurysms), syphilis and vasculitides
42
Mycotic aneurysms (infections)
from embolization of a septic embolus (infective endocarditis)
from extension of an adjacent suppurative process
from circulating organisms infecting the arterial wall
43
aneurysms vs pseudoaneurysms
True aneurysm – bounded by arterial wall component or myocardium
Saccular aneurysm – appears rounded
Fusiform aneurysm – involves long segment of artery and is not rounded
False aneurysm (pseudoaneurysm) = hematoma secondary to transmural rupture
44
Abdominal Aortic Aneurysms (AAA)
Usually below the renal arteries
Renal complications with involvement of renal arteries
M>F, smokers and age >50 years
```
Inflammatory AAA (5-10%) - lymphocytes, plasma cells and macrophages +/- giant cells (uncertain cause and occur at younger age)
IgG4 related disease with aortis and periaortitis - infiltrating IgG4+ plasma cells (may affect pancreas, biliary system, and salivary gland with fibrosis)
Mycotic abdominal aortic aneurysms - atherosclerotic AAAs that have become infected (Salmonella gastroenteritis)
```
45
Thoracic aortic aneurysms
also occur with similar complications (to AAAs) plus involvement of coronary ostia
46
Clinical consequences of aortic aneurysms
risk of rupture. Usually repair those over 5 cm.
Obstruction of a vessel leading to ischemic tissue injury
Embolism from atheroma or mural thrombus
Impingement on an adjacent structure, such as compression of a ureter or erosion of vertebrae
Presentation as an abdominal mass (often palpably pulsating) that simulates a tumor
47
Syphilitic (Luetic) Aneurysms
Obliterative endarteritis in tertiary stage of syphilis (lues) involves vasa vasorum (arterioles) of the thoracic aorta
Syphilitic aortitis - obliterative endarteritis of vasa → ischemic injury of the media → loss of the medial elastic fibers and muscle cells
Can lead to aneurysmal dilation that can include the aortic annulus leading to aortic valve incompetence
Can involve coronary ostia
48
AORTIC DISSECTION (DISSECTING HEMATOMA)
Dissection of blood between planes of the media
May or may not occur with an aneurysm
*** > 90% occur in men 40-60 with hypertension
Arteriolosclerosis → smooth muscle cell loss
In younger people may be connective tissue disorder (Marfan, Ehlers-Danlos, Vit. C deficiency)
Can be iatrogenic (arterial cannulation)
Rarely occurs during or following pregnancy
Occasionally 2ry to vasa vasorum rupture
49
terminology: genetic and general word for narrowing of arteries
arteriosclerosis
50
terminology: lesion of large arteries with formation of atheroma
atherosclerosis
51
terminology: lesion of small vessels
arteriolosclerosis
52
Dissection - Clinical
Sudden onset of excruciating pain, usually involves anterior chest, radiating to the back, and moving downward
*** Most common cause of death is rupture into the body cavities
Retrograde dissection into the aortic root → aortic valvular apparatus dysfunction with aortic insufficiency
Can dissect into neck, coronary, renal, mesenteric, or iliac arteries, and compression of spinal arteries may cause transverse myelitis
Occasionally the dissection can rupture back into vessel lumen causing a dual lumen vessel
*** Aggressive treatment of HTN may halt dissection
53
substantial atherosclerosis or other cause of medial scarring such as syphilis
dissection is unusual here.
54
Marfan Syndrome
Loss of function mutation of fibrillin
Heterozygotes have clinical symptoms
> 500 mutations of FBN1 gene (15q21) for fibrillin 1
Mutant fibrillin 1 prevents the assembly of normal microfibrils
With ↓fibrillin-1 there is ↑TGF-β activity and serum levels
Fibrillin 1 is involved in forming a complex that binds and inactivates TBF-β
TGF-β involved in embryonic development, cell growth and apoptosis
TGF-β ↑ collagen production and extracellular matrix (ECM) remodeling
leads to overgrowth of bones and myxomatous changes in mitral valves
55
called Loeys-Dietz syndrome
Mutations in the TGF-β receptors give rise to a similar syndrome
56
Principal Clinical Manifestations of Marfan syndrome
Skeleton: Slender with abnormally long legs, arms, and fingers (arachnodactyly); high-arched palate; hyperextensibility of joints; spinal deformities (kyphoscoliosis); pectus excavatum or pigeon-breast
Eyes: Bilateral dislocation (subluxation/ectopia lentis) of lens from weakness suspensory ligaments (ciliary zonules holding lens are made up exclusively of fibrillin)
Cardiovascular system: Aneurysmal dilation and aortic dissection; dilation of the aortic valve ring (aortic incompetence); mitral and tricuspid valve floppy valve syndrome giving rise to congestive cardiac failure
Death from aortic rupture is the most common cause of death
Can occur at any age
Cardiac failure also causes deaths
57
Large vessel vasculitis
granulomatous disease
58
med vessel vasculitis
immune complex mediated
anti-endothelial cell antibodies (e.g. Kawasaki disease)
59
Small vessel vasculitis (types)
Paucity of immune complexes (often with ANCA):
- without asthma or granulomas (microscopic polyangitis)
- granulomas, no asthma- Wegener granulomatosis
- Eosinophilia, asthma, and granulomas (Churg Strauss)
Immunce complex mediated:
-SLE
IgA (Henoch-schoenlein purpura)
Cyoglobulin
60
Vasculitis from direct infection
```
Bacterial (neisseria)
Rickettsial (Rocky Mountain spotted fever)
Spirochetal (Syphilis)
Fungal (aspergillosis, mucormycoses)
Viral (herpes-zoster, varicella)
```
61
Immunologic vasculitis
Immune complex-mediated
Infection-induced (hepatitis B and hepatitis C viruses)
Henoch-Schonlein purpura
Systemic Lupus Erythematosus and rheumatoid arthritis
Polyarteritis nodosa (HBsAg/HBsAg-Ab)
Drug-induced hypersensitivity reactions
Cryoglobulinemia
Serum sickness
Antineutrophil cytoplasmic antibody (ANCA)-mediated (pauci-immune)
Wegener granulomatosis - PR3-ANCA (c-ANCA)
Microscopic polyangiitis/polyarteritis- MPO-ANCA (p-ANCA)
Churg-Strauss syndrome- MPO- ANCA (p-ANCA)
```
Direct antibody mediated
Goodpasture syndrome (anti-glomerular basement membrane Ab)
Kawasaki disease (anti-endothelial Ab and also anti smooth muscle cell Ab)
```
62
Cell- Mediated vasculitis
Organ allograft rejection
Inflammatory bowel disease
Paraneoplastic vasculitis
63
Unknown vasculitis
```
Giant cell (temporal) vasculitis
Takayasu arteritis
```
64
Infectious Vasculitis
Sometimes from direct invasion of bacteria (pseudomonas) or fungi (Aspergillus and mucormycosis)
Can frequently accompany bacterial pneumonia
Can occur adjacent to caseous tuberculous abscesses
Can occur in superficial cerebral vessels in meningitis
Can be secondary to septic emboli
May result in a mycotic aneurysm or induce thrombosis and infarction
65
Non-specific Constitutional Symptoms with Vasculitis
```
Fever
Weight loss
Myalgia
Arthralgia
Malaise
Fatigue
```
66
Giant Cell (Temporal) Arteritis
Granulomatous arteritis of aorta, major branches and often the temporal arteries (can be tender on palpation)
Usually >50 and often associated with polymyalgia rheumatica
Most common vasculitis of elderly in US
Ophthalmic arterial involvement →diplopia and permanent blindness
May cause giant cell aortitis and thoracic aortic aneurysm
Can involve coronary arteries
67
Takayasu arteritis
Granulomatous inflammation of the aorta and its major branches.
Patients usually under 50
Marked weakening of pulses (Pulseless Disease) and reduced blood pressures of upper extremities
68
Kawasaki disease
Arteritis involving large, medium-sized or small arteries
Usually self limited in children
Coronary arteries often involved +/- aneurysms
Associated with mucocutaneous lymph node syndrome
- acute usually self-limited disease with fever, conjunctival and oral erythema (strawberry tongue) and a desquamative skin rash
69
Thromboangiitis Obliterans (Buerger Disease)
Segmental, thrombosing, acute and chronic inflammation
of medium-sized and small arteries (tibial and radial), and extending to veins and nerves of the extremities
Previously occurred almost exclusively among heavy cigarette-smoking men, increasing in women
Begins before age 35 in most cases
Chronic ulcerations of the toes, feet, or fingers and gangrene
Secondary Raynaud phenomenon
Exercise induced instep claudication
Nodular phlebitis
Severe pain, even at rest (nerve involvement)
70
Polyarteritis nodosa (classic)
Necrotizing inflammation in small to medium arteries, arterioles, capillaries or venules
Usually of young adults
Renal arterial involvement causes deaths
No glomerulonephritis
30% have hepatitis B surface Ag/Ab complexes
Malaise, fever, weight loss, HTN, abdominal pain and melena, muscular aches/pains, ulcers, infarcts, peripheral neuritis (mostly motor)
Rx – steroids and cyclophosphamide
71
Behçet disease
Neutrophilic vasculitis of small to medium arteries
Triad
recurrent oral aphthous ulcers
genital ulcers
uveitis
Can have positive pathergy test – minor trauma,
(sterile pinprick) causes exaggerated reaction
72
Granulomatosis with polyangiitis (Wegener granulomatosis)
Triad –
Acute necrotizing granulomas of the upper and/or lower respiratory tract
Necrotizing or granulomatous vasculitis in the lungs and upper airways +/-other sites (eyes, skin, heart)
Renal disease with focal necrotizing glomerulonephritis (crescentic) with hematuria/proteinuria +/- renal failure
c-ANCA (PR3-ANCA) - antineutrophil cytoplasmic autoantibodies targeting proteinase 3 (PR3) in azurophilic granules are highly specific
present in 95%
```
Clinical presentation
M > F; ~40 years
Persistent pneumonitis; bilateral nodular and cavitary infiltrates in 95%
Chronic sinusitis in 90%
Mucosal ulcerations of the nasopharynx in 75%
Renal disease in 80%
Skin rashes
Muscle pains
Articular involvement
Mononeuritis or polyneuritis
Fever
```
Untreated disease is malignant; 80% of patients die within 1 year
Responds to immunosupression (steroids, chemo, and anti-TNF)
73
Churg-Strauss syndrome
= allergic granulomatosis and angiitis
Eosinophil-rich and granulomatous necrotizing vasculitis
Possible hyper-responsiveness to allergen
Strong association with allergic rhinitis, bronchial asthma, lung infiltrates
Blood eosinophilia
**p-ANCA (MPO-ANCA) perinuclear antimyeloperoxidase in 50%
Palpable purpura
Involves respiratory tract
**Coronary arteritis and eosinophilic myocarditis are the principal causes of morbidity and mortality
74
Microscopic polyangiitis
= leukocytoclastic vasculitis
Necrotizing vasculitis with few or no immune deposits (pauci-immune) involving capillaries and small vessels.
Possible reaction to drugs, organisms, or exogenous or tumor proteins
p-ANCA (MPO-ANCA) targeting perinuclear antimyeloperoxidase in lysosomes + in >70%
```
“Palpable purpura" of skin
Necrotizing glomerulonephritis (90% of patients) Pulmonary capillaritis is common
Hemoptysis, arthralgia, abdominal pain or bleeding, hematuria, proteinuria, hemorrhage, and muscle pain or weakness
```
75
Vasculitis Associated with Other Disorders
Seen with rheumatoid arthritis, SLE, malignancy, mixed cryoglobulinemia and Henoch-Schönlein purpura
Vasculitis resembling hypersensitivity angiitis or classic polyarteritis nodosa
Rheumatoid vasculitis after long-standing, severe rheumatoid arthritis
visceral infarction
may cause a clinically significant aortitis
Lupus vasculitis
vs antiphospholipid antibody syndrome
aggressive anti-inflammatory therapy
vs aggressive anticoagulant therapy
76
Hypothermia
Prolonged exposure to low ambient temperature
At about 90°F, loss of consciousness occurs, followed by bradycardia and atrial fibrillation at lower core temperatures
Direct effects: Physical disruptions and high salt concentrations within cells due to crystallization of the intra- and extracellular water
Indirect effects: Circulatory changes
Vasoconstriction and increased permeability (leading to edema)
Alcohol causes vasodilation lowering body temperature faster
77
diffferent effects of hypothermia
Frostnip
Vasoconstriction involving nose, ears, hands, feet
Chilblain (Perniones/Perniosis)
Nonfreezing temperatures and damp conditions
Chronic, recurrent vasculitis with red raised lesions
Immersion (trench) foot
Feet have been wet, but not freezing
May not heal, chronic pain, edema and blotchy discoloration
Often produces a superficial, moist, liquefaction gangrene
Frostbite
Sudden sharp drops in temperature that are persistent
Vasoconstriction and increased viscosity of the blood
Hyperemia and edema, large, clear blisters, vesicles filled with hemorrhagic fluid to complete gangrene
78
Raynaud Phenomenon
Pallor or cyanosis of the digits of the hands or feet and, infrequently, tips of the nose or ears
Primary Raynaud phenomenon (disease)
Cold or emotion-induced vasoconstriction
Patients should undergo evaluation to rule out an underlying 2ry cause (approximately 10% of patients have secondary Raynaud phenomenon)
Late in the course intimal thickening can appear
Median age is 14 years, prevalence 3% - 5% of population
Secondary Raynaud phenomenon
Arterial insufficiency caused by various conditions
SLE, systemic sclerosis (scleroderma), atherosclerosis, or Buerger disease
79
Varicose Veins
Dilated, tortuous veins
increased intraluminal pressure and loss of vessel wall support
Valves incompetent
venous stasis, congestion, edema, pain, and thrombosis
Prevalence 10-30% (10-20% ♂; 25-33% ♀)
At risk
>50 y/o
obese
women - elevated venous pressure in pregnancy
long periods of standing or long car or airplane rides -lead to venous stasis and pedal edema (simple orthostatic edema)
Can develop stasis dermatitis (brawny induration)
Variation in the thickness of the vein wall (dilation in some areas and hypertrophy of the smooth muscle and subintimal fibrosis in others)
** Phlebosclerosis - elastic tissue degeneration and spotty calcifications within the media
80
Thrombophlebitis & Phlebothrombosis
90% in deep leg veins
```
Predisposing factors:
Cardiac failure
Pregnancy
Obesity
Postoperative state
Prolonged bed rest or immobilization
Estrogen therapy (2X)
Oral contraceptives (3-6X)
Genetic hypercoagulability syndromes
** Neoplasia, particularly adenocarcinomas of the pancreas, colon, or lung, (paraneoplastic syndrome)
*** Migratory Thrombophlebitis (Trousseau syndrome/sign)- thrombi disappear in one site and appear in a new site
(do not confuse with Trousseau phenomenon/sign from hypocalcemia)
```
** Pulmonary embolism is common complication and may be presenting symptom
** Pain can be elicited on squeezing the calf muscles or forced dorsiflexion of the foot (Homan sign)
Plegmasia alba dolens (painful white leg) - iliofemoral venous thrombosis in pregnant or recently pregnant women
Also occurs in periprostatic veins and pelvic venous plexus
81
Vena Cava Syndromes
Superior Vena Cava Syndrome
* Usually neoplasm compresses or invades with cyanosis and dilation of the veins of the head, neck, and arms
If pulmonary vessels also compressed have respiratory distress
Inferior Vena Cava Syndrome
* Neoplasm compresses or penetrates (renal, hepatic or adrenal cortex carcinomas) or a thrombus * propagates upward with leg edema, distention of lower abdomen superficial collateral veins
With renal vein involvement massive proteinuria
82
Lymphangitis & Lymphedema
* Lymphangitis - Infections involving lymphatics with red streaks
(Group A beta hemolytic streptococci)
in severe cases produces cellulitis or focal abscesses
* Acute lymphadenitis - red streaks with painful enlarged regional lymph nodes
* Obstructive (secondary) lymphedema – dilation of lymphatics with increased interstitial fluid caused by
malignant tumors obstructing lymphatic channels or lymph nodes
removal of regional groups of lymph nodes
postirradiation fibrosis
filariasis
postinflammatory thrombosis and scarring
** Chronic edema can lead to thickened skin (brawny induration or peau d’orange)
83
Primary lymphedema (three forms)
isolated congenital defect (simple congenital lymphedema)
familial Milroy disease (heredofamilial congenital lymphedema) have lymphatic agenesis or hypoplasia
lymphedema praecox - age 10 to 25 years, usually female, unknown cause with edema starting in the feet and slowly accumulating throughout life (extremity may swell to many times its normal size and the process may extend to the trunk)
84
Chylous ascites, chylothorax, and chylopericardium -
caused by rupture of obstructed, dilated lymphatics into the peritoneum, pleural cavity, or pericardium
85
Vascular Ectasias
Telangiectasia - congenital anomaly or acquired permanent exaggeration of preformed vessels
composed of prominent capillaries, venules, and arterioles
Nevus Flammeus (birthmark) - most common form of ectasia (usually head and neck)
Port-wine stain - Nevus flammeus that may grow proportionately with child with no tendency to fade
86
Sturge-Weber syndrome
```
uncommon congenital disorder
venous angiomatous masses in the
leptomeninges
ipsilateral port-wine nevi with
trigeminal nerve distribution
often associated with mental retardation,
seizures, hemiplegia, and
radiopacities in the skull
```
87
Spider Telangiectasia (Arterial Spider)
dilated subcutaneous arteries or arterioles about a
central core that blanches when pressure is applied
to its center.
usually face, neck, or upper chest
Most frequent in pregnant women and in cirrhosis (hyperestrinism)
88
Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu Disease) –
Congenital malformations consisting of dilated capillaries and veins
Present at birth and distributed widely over the skin and mucous membranes of the oral cavity, lips, and respiratory, gastrointestinal, and urinary tracts
Autosomal dominant mutations
in TGF-β signaling pathway genes
89
Bacillary Angiomatosis
Opportunistic infection of immunocompromised persons (AIDS)
Involves skin, bone, brain, and other organs
Bartonella species -Gram-negative bacilli
B. henselae –domestic cat reservoir with cat flea its vector
Same agent causes cat-scratch disease
B. quintana - human reservoir with human body louse vector
Same agent causes trench fever
Host induction of hypoxia-inducible factor 1 (HIF-1α) →↑ VEGF →↑ vascularity
Rx- macrolide antibiotics (erythromycin)
Closely related vascular lesion in liver and spleen called bacillary peliosis
90
Hemangiomas
Hemangiomas constitute 7% of all benign tumors in infancy and childhood
Common in skin (majority) and liver (1/3)
Malignant transformation rare
Angiomatosis - involves large segment of the body (such as an entire extremity)
91
Capillary hemangiomas
most common vascular tumor
in skin, subcutaneous tissues, and mucous membranes, but can be in any organ with a vascular supply
lumina may thrombose
rupture of vessels causes scarring (hemosiderin pigment occasionally found)
92
Juvenile hemangioma
"strawberry type" capillary hemangioma of the skin of newborns
1 in 200 births
grows rapidly in the first few months
regresses by age 7 in 75% to 90%
93
Pyogenic granuloma (lobular capillary hemangioma)
```
polypoid capillary hemangioma
1/3 develop after trauma
rapidly growing red nodule
skin or gingival or oral mucosae
bleed easily and often ulcerated
edema and inflammatory infiltrate
(resemble exuberant granulation tissue)
```
94
Granuloma gravidarum
(pregnancy tumor) - pyogenic granuloma that occurs in the gingiva of 1% of pregnant women (regresses after delivery)
95
Cavernous Hemangioma
Larger, less circumscribed, and
more frequently involves deep structures
than capillary hemangiomas
May be locally destructive
No tendency to regress
Intravascular thrombosis with associated dystrophic calcification
Hemangiomas of the brain threatening since cause pressure symptoms or rupture
96
Hemangioblastomas
in Von Hippel-Lindau disease
Angiomatous lesions cerebellum, brainstem, and eye
Cystic neoplasms in the pancreas and liver
Other visceral neoplasms
97
Lymphangioma Circumscriptum
= Capillary (simple) lymphangioma
small lymphatic channels
tend to occur subcutaneously in the head and neck and in axilla
absence of luminal erythrocytes
98
Cavernous Lymphangioma
= cystic hygroma
in children in the neck or axilla and, rarely, retroperitoneum
massively dilated, cystic lymphatic spaces
cystic hygromas (lymphangioma colli) of the neck occur in Turner syndrome
99
Kaposi Sarcoma Pathogenesis
Human herpesvirus 8 [HHV-8] (KS-associated herpesvirus [KSHV]) proteins isolated in 1994 from a skin lesion of AIDS patient
95% of KS lesions are infected with KSHV (ɣ-herpesvirus subfamily w/ EBV)
KSHV infects endothelial cells
Viral induced G-protein induces VEGF production
** Most primary KSHV infections are asymptomatic!
Immunosuppression and AIDS appear to be important cofactors
In early stages KS appears to be a reactive, polyclonal lesion with only a
few cells infected
100
Kaposi Sarcoma Stages
Patch stage- pink to purple solitary or multiple macules
Dilated angulated blood vessels and chronic inflammatory cells (lesions difficult to distinguish from granulation tissue)
Plaque stage- larger, violaceous dermal jagged vascular channels lined by plump spindle cells with occasional mitoses with RBC extravasation**
Nodular stage – raised nodular lesions
often accompanied by involvement of lymph nodes and of viscera
sheets of spindle cells with mitotic figures and slit-like spaces that often contain rows of red cells
101
3 major types of kaposi sarcoma
HIV associated
transplant associated
endemic- African or Ashkenazi Jews
102
Hemangioendothelioma
Histologic features and clinical behavior intermediate between hemangiomas and angiosarcomas
Epithelioid hemangioendothelioma
vascular tumor occurring around medium and large veins in the soft tissue of adults
inconspicuous well-defined vascular channels and tumor cells are plump and often cuboidal
most cured by excision
103
Angiosarcoma
**Can be induced by radiation and foreign material left in the body
Histology varies from differentiated (hemangiosarcoma) to anaplastic
Immunohistochemistry: CD31, CD34, Factor VIII or vWF
Cutaneous angiosarcoma
Small, often asymptomatic, red nodules
Eventually become large, fleshy, pale, gray-white, with central softening, necrosis and hemorrhage
Hepatic angiosarcomas
Associated with carcinogens [arsenic, Thorotrast and vinyl chloride**]
Many years between exposure and tumors
Lymphangiosarcoma
Arise in chronic lymphedema (approximately 10 years following radical mastectomy)**
104
Glomus Tumor (Glomangioma)
Benign often painful** tumor
From modified cells of the glomus body
(arteriovenous anastomosis involved in thermoregulation)
Most commonly distal digit
Small slightly elevated, rounded, red-blue, firm nodules
minute foci of fresh hemorrhage if under the fingernails
Specialized glomus cells (modified smooth muscle cells on electron microscopy) arranged around vessels
105
Balloon Angioplasty
Balloon dilation of a stenosis via
percutaneous transluminal
coronary angioplasty)
Causes plaque rupture, medial
dissection, and stretching of the
media
```
Complications:
Abrupt reclosure (extensive circumferential or longitudinal dissection, thrombosis)
Proliferative in-stent restenosis (intimal thickening in 30% to 50% of patients within the first 4 to 6 months)
```
106
Vascular Stents
Expandable tubes of metallic mesh
Used in 90% of angioplasties
Limit elastic recoil and mechanically
prevent vascular spasm
Damage endothelium and stretch wall
Initially covered by platelet-fibrin coating
and later by endothelium-lined neointima
```
Complications
Early - thrombosis
use platelet antagonists)
Late - intimal thickening
use antiproliferative drugs, e.g. paclitaxel or sirolimus
```
107
Vascular Grafts
Synthetic or autologous
Large-diameter (12 to 18 mm) Dacron grafts in high-flow locations such as the aorta
Small-diameter fabric grafts (up to 6 to 8 mm) perform less well (thrombotic occlusion)
Endothelialization of clinical grafts is unusual
* neointima in a 12- to 15-mm zone near the anastomosis
* pseudointima with thrombus or cells other than endothelial cells lining remainder of graft
