Blood Vessel Disease 
| Cell Function |
Atherosclerosis |
| Hypertension |
Vasculitis |
| Aneurysms |
Venous Disease |
| Lymphatic Disease |
|
This category represents the most important group of disorders with respect to human
morbidity and mortality. The primary mechanisms of vascular disfunction
include:
1. Lumenal narrowing
2. Endothelial cell injury
3. Vessel wall weakening
Endothelial Cell Function:
1. Semipermeable barrier
2. Control of blood coagulability
Inhibition - prostacyclin
Stimulation - von Willebrand Factor
3. Extracellular matrix synthesis
4. Blood flow regulation
Vasoconstriction - ACE, endothelin
Vasodilation - prostacyclin, NO/EDRF
5. Regulation of inflammation/immune reactivity - HLA's, adhesion
molecules, IL
6. Regulation of cell growth - PDGF, FGF
7. LDL oxidation
Smooth Muscle Cell Function:
1. Blood flow regulation
2. Extracellular matrix synthesis
3. Regulation of cell growth
4. Proliferation
5. Migration
Arteriosclerosis
This is a category of diseases that have in common:
1. Wall thickening
2. Inelasticity
In order of importance with respect to human mortality and morbidity, this
category includes:
1. Atherosclerosis
2. Arteriolosclerosis
3. Monckberg's medial calcific sclerosis
Atherosclerosis
This disease is responsible for 50% of all deaths in the Western world. The
development of an intimal atheroma (plaque) disrupts flow (turbulence),
narrows lumenal diameter (ischemia), weakens underlying media
(aneurysms), and contributes to endothelial injury (thrombosis). This
condition begins in childhood but typically does not manifest until patients are in
their middle adult life.
Risk Factors:
Unmodifiable:
1. Age - The risk for complication increases about 6X from age
40-60.
2. Sex - Males 5:1 females
Females by age 80 equal
3. Familial Predisposition -
Multifactorial
Hypercholesterolemia
Dyslipoproteinemia
Modifiable
1. Hyperlipidemia
High LDL (cholesterol)
High VLDL (triglycerides)
Low HDL
2. Hypertension
BP> 160/95 5X risk for IHD than
BP< 140/90
3. Smoking > 1pck/day 2X risk for IHD
4. Diabetes mellitus 2X risk for IHD
100X risk for l.e. gangrene
5. Lack of exercise
6. Type A' personality
7. Obesity
Pathogenesis: Reaction to Cell Injury Theory
1. Overtime, non-denuding endothelial cell injury (viruses, toxins, hypoxia,
shear stress, turbulence) leads to an increase in endothelial permeability.
2. Lipid oxidation increases as a response from increased transport
(endothelial cells and macrophages) and as a response to localized
inflammation.
3. Release of growth factors and cytokines results in SMC proliferation,
migration and ongoing cell injury.
4. Plaques progress from fatty streaks in childhood to fibrofatty plaques of
adulthood. A critical event is the development of plaque complication:
A. Calcification
B. Ulceration - Embolization/Thrombosis
C. Hemorrhage
Type of damage is dependent on caliber of vessel involved.
Clinical:
1. Aorta - Aneurysm/rupture
2. Coronary a. - Obstruction /ischemia /MI/CIHD/sudden cardiac death
3. Cerebral a. - Stroke/TIA/ischemic encephalopathy
4. Peripheral a. - Leg gangrene/mesenteric occlusion/renal hypertension
Atherosclerosis is a multifactorial disease involving:
1. Endothelial dysfunction
2. Chronic inflammation
3. SMC proliferation
4. Extracellular matrix deposition
5. Lipid accumulation
6. Thrombosis
Hypertension
This is a common disorder (25% of U.S.) defined as sustained diastolic >
90mmHg. and sustained systolic > 140mmHg.. Patients that develop
hypertension have two basic problems to deal with. The first is identifying the
cause of the elevated blood pressure and the second is dealing with the impact
that this elevated b.p. has on the vasculature (arteriolosclerosis).
Primary Hypertension
Approximately 90% of all identified hypertensive patients have this form of the
disease. It is defined primarily by the lack of a definitive mechanism. It is
believed to be a consequence of genetic, environmental, and other unknown
alterations in the complex control mechanisms of blood pressure.
Examples:
1. Pressure dependent Na excretion:
Genetic variances in renal sodium excretion lead to Na
retention. With Na retention and fluid volume expansion,
reactive vasoconstriction occurs. As b.p. increases, Na
excretion increases leading to a new steady state.
2. Intracellular Na retention:
Defects in Na/K pump function lead to intracellular Na
accumulation. In smooth muscle, Na/Ca co-transport leads to
net Ca accumulation and an increase in vascular tone.
Secondary Hypertension
Patients with this form of the disease have clearly defined defects in
organs/tissue that directly interfere with b.p. regulation.
Examples: 1. Renal arterial stenosis
2. Renal disease
3. Cushing's syndrome (ACTH)
4. Thyrotoxicosis
5. Pheochromocytoma
6. Coarctation of the aorta
7. Vascular inflammation
8. Increased intracranial pressure
9. Psychogenic
Benign Hypertension
Patients have a slowly progressive increase in blood pressure with often
asymptomatic or minor clinical complications.
Malignant Hypertension
Patients rapidly develop tissue injurious blood pressure (Diastolic> 120mmHg.).
With retinal, brain and kidney damage.
Hypertensive Vascular Injury
Hyaline Arteriolosclerosis
Hyaline (blood proteins) deposition within the intima leads to vascular wall
thickening and luminal narrowing in combination with SMC hypertrophy.
This process is characteristic of changes seen in the kidney
(nephrosclerosis).
Hyperplastic Arteriolosclerosis
Onion skin lamination of arteriole walls combined with SMC hypertrophy
and hyperplasia. This reaction is characteristic of malignant hypertension
(necrotizing arteriolitis).
Vasculitis
General term referring to inflammation of arteries and veins. Inflammation of
the aorta is termed aortitis.
Polyarteritis Nodosa (PAN)
Arterial inflammation affecting medium and small arteries. Common sites
include the kidney, heart, and skeletal muscle. Although the etiology is
unknown, 30% of patients show the presence of hepatitis B antigen in
circulation.
Clinical:
Localized transmural inflammation
Thrombosis/infarction
Neutrophil infiltration
Fibrinoid necrosis
Recurrent inflammation
Malaise, fever, weight loss
Renal failure
Wegener's Granulomatosus
Vascular inflammation affecting adults with unknown etiology (autoimmune?).
Clinical: 1. Upper resp. tract inflam.
2. Lower resp. tract inflam.
3. Glomerular nephritis
Temporal (Giant Cell) Arteritis
The most common form of vascular inflammation. This disease affects the
major arteries of the head and neck. Typical patients are female over the age of
50.
Clinical: Pain over affected site
Fever, malaise, weight loss
Unilateral diplopia or vision loss
Blindness
Takayasu's Arteritis (Pulseless Disease)
This chronic inflammatory disease is mainly restricted to the aortic arch
and its major branches. Fibrinoid necrosis of these vessels leads to
reduced flow to upper extremities, visual disturbances, and neurologic
damage.
Kawasaki's Disease (Mucocutaneous Lymph Node Syndrome)
Vascular inflammation affecting the coronary arteries of infants and young
children. Disease is acute and may lead to MI.
Thromboangiitis Obliterans (Buerger's Disease)
Inflammatory vascular disease affecting arteries and veins of the
extremities. The disease has a remitting/relapsing course and is closely
associated with cigarette smoking. Primarily males (35-50), its incidence
is increasing in women.
Clinical: Raynaud's phenomenon
Severe pain (neural involvement)
Chronic ulceration
Gangrene
Aneurysms
This term refers to abnormal dilatations of arteries or veins but is most often
seen on the arterial side. The most common lesions that lead to wall weakness
are:
1. Atherosclerosis
2. Cystic medial necrosis
Atherosclerotic Aneurysms
This is the most common cause of aneurysms. They occur most often in
the aorta and more frequently in the abdominal aorta between the origin of
the renal arteries and the bifurcation of the common iliac a..
Clinical: male:female 5:1
Age > 50
Thrombosis/Embolization
Pressure erosion (vertebral bodies)
Pulsatile mass
Rupture
Course: Mortality rate is dependent on size (> 6 cm., 50% in 10 yrs)
Surgical mortality <5% prior to rupture and 50% after
rupture.
Aortic Dissection
Entry of blood into the arterial wall through an intimal tear results in
parallel dissection of the medial laminar planes. The most common
predisposing condition is hypertension (90%). Another factor is the
development of cystic medial necrosis in pathients with Marfan's
syndrome.
Clinical: Severe pain confused with MI
Double-barrel aorta
Cardiac tamponade
Venous Disorders
With few exceptions, venous disorders are causes of morbidity, discomfort, and
cosmetic problems, but are rarely lethal.
Varicose Veins
The most common form are the superficial venous varicosities of the lower
extremities. The primary cause is prolonged elevation of venous pressure.
Varicosities of the hemorrhoidal plexus (hemorrhoids) tend to form as a
result of pelvic congestion (pregnancy, constipation, straining).
Esophageal varices result from liver congestion often seen in conjunction
with chronic alcoholism and can be lethal.
Clinical: Asymptomatic
Pain
Local edema
Vascular insufficiency
Ulceration/bleeding
Phlebothrombosis/Thrombophlebitis
Condition affecting the deep veins of the lower extremities. The
terminology is often misleading. Clinicians often use the term
thrombophlebitis to describe all cases of deep vein thrombosis. This term
is also used to specifically describe the development of deep vein
thrombosis resulting from prior venous wall inflammation.
The term phlebothrombosis is used to refer to cases of deep vein
thrombosis resulting primarily from venous stasis (cardiac failure,
immobilization, surgery, abdominal cancer, severe burns).
Clinical: Asymptomatic
Inflammation/pain
Pulmonary embolism
Pulmonary infarction
Lymphatic Disorders
The lymphatic channels are often obstructed by infection (lymphangitis) with
the most common organism, group A beta-hemolytic streptococcus.
Obstruction of the lymphatics by surgery, fibrosis, cancer, infection (filariasis)
leads to lymphedema. Interstitial fluid accumulation leads to fibrosis (peau
d'orange) and ulceration.
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