Alterations of cardiovascular function Flashcards
Vessel diameter pattern
Large at aorta -> smaller until smallest at capillaries -> larger again until largest at venae caveae
Total cross-sectional area pattern of blood vessels
smallest at aorta and vanae caveae and largest at capillaries
Average blood pressure patterns
Largest at aorta and smallest at venae caveae
Velocity of blood flow patter
- volume makes blood flow faster in veins even though there is low BP
- highest at aorta (starting as a river), lowest at capillaries (like in a field) and high again at venae caveae *going back into a river)
Atherosclerosis
- most common type of arteriosclerosis which is a group of 3 diseases
- “hardening of the arteries”
- arteries become very stiff and thickened due to the deposition of fibro-fatty plaques between layers of the vessel wall
Between what two layers of the vessel wall do the fibro-fatty plaques deposit?
tunica media and tunica intima
Epidemiology of atherosclerosis
- no disease in the U.S is responsible for more deaths
- very prevalent - North America, Europe, Austraila, Russia and developed nations
- mortality rate for ischemic heart disease in USA is 6x higher than that of Japan
Risk factors for atherosclerosis
- Age: risk rises with each decade
- Sex: Males more prone than females
- Familial Predisposition
- Acquired risk factors
Age as a risk factor for atherosclerosis
- early stages of atherosclerotic disease are seen in young children
- from age 40 to age 60 there is a fivefold increase in incidence of myocardial infarct
Sex as a risk factor for atherosclerosis
- between ages 35 and 55, mortality rate for white women is one fifth that of white men
- after menopause, risk increases in women, rates are same for both sexes in their 60’s and 70’s
Familial predisposition as a risk factor for atherosclerosis
- family risk for hypertension or diabetes
- high blood lipid levels due to genetics
Acquired Risk Factors for atherosclerosis
“the big 4”
- high blood lipid levels due to diet
- hypertension
- cigarette smoking
- diabetes mellitus
Acquired Risk Factors: Hyperlipidemia
- high total cholesterol levels increase risk of atherosclerosis
- atherosclerosis is very unusual with total serum cholesterol levels below 150 mg/dl
Different types of cholesterol
LDL and HDL
-lipoproteins are carrier molecules which transport cholesterol in the bloodstream (hypercholesterolemia)
LDL
- low-density lipoproteins: “bad cholesterol”
- believed to mobilize lipid into the bloodstream
HDL
- high-density lipoproteins: “good cholesterol”
- high = healthy
- believed to mobilize lipid from cells and from plaques to the liver for excretion in the bile (taking from blood into tissues)
Significance of types of cholesterol
- a high level of LDL is a strong indicator of risk of coronary and atherosclerotic disease
- increased LDL has been shown to results in endothelial dysfunction (damaged cause clotting)
- HDL’s are though to prevent or relay atherogenesis and to thus be protective
- exercise raises the HDL level
- Obesity and smoking both lower the HDL level.
Acquired Risk Factors: Hypertension
- may be more important than hypercholesterolemia after age 45
- men age 45-62 whose blood pressure exceeds 160/95 mmHg have a fivefold greater risk than men with blood pressures 140/90 mmHg.
Acquired Risk Factors: Smoking
- smoking one or more packs of cigarettes a day for several years increases the death rate from ischemic heart disease by up to 200%
- cessation of smoking reduces this risk with time
Acquired Risk Factors: Diabetes Mellitus
- specifically type II
- diabetes induces hypercholesterolemia
- the incidence of myocardial infarction is twice as high in diabetics
- diabetics also have an increased risk of stroke
- diabetics have a 100-fold increased risk of atherosclerosis-induced gangrene of the lower extremities (poor circulation)
Other risk factors of atherosclerosis
Other risk factors- difficult to measure:
- insufficient regular physical activity (raises HDL when active)
- competitive, stressful life style with “type A” personality behavior
- use of oral contraceptives
- multiple risk factors impose more than an additive effect
- Atherosclerosis may also appear in the absence of any apparent risk factors
Oxidized LDL
- smoking lead to this
- is more readily ingested by macrophages
- chemotactic for circulating monocytes
- increases monocyte adhesion
- inhibits motility of macrophages in the lesions
- stimulates release of chemical mediators
- cytotoxic to endothelial and smooth muscles cells
- antioxidants (vitamin E) may help provide some protection against atherosclerosis
Steps to atherosclerosis
- chronic endothelial enjury
- endothelial dysfunction
- smooth muscle emigration from media to intima
- Macrophages and smooth muscle cells engulf lipid
- Smooth muscle proliferation, collegen and other ECM deposition, extracellular lipid
- What does chronic endothelial injury allow?
LDL lipoproteins to accumulate in the intima and become oxidized
What are some causes of endothelial injury?
- Hyperlipidemia
- Hypertension
- Smoking
- Immune reactions
- Hemodynamic factors
- Toxins
- Endothelial dysfunction
- for example: increased permeability, leukocyte adhesion
- monocyte adhesion and emigration
- monocytes adhere and migrate between endothelial cells and engulf LDL’s to become foam cells
- Smooth muscle emigration from media to intima
- macrophage activation
- smooth muscle cells migrate towards the intimate and proliferate
- Macrophages and smooth muscle cells engulf lipid
- the accumulation of foam cells show up as fatty streaks and induce an inflammatory response
- the smooth muscle engulfing lipid are also referred to as foam cells
- Smooth muscle proliferation, collagen and other ECM deposition, extracellular lipid
- Collagen and elastin are produced by the smooth muscle cells forming a fibrous plaque
- called a fibrofatty atheroma
Further progression of atherosclerosis
- the plaque can ulcerate or rupture, further injuring the endothelial cells
- platelets become stimulated and forming thrombi and thromboemboli
- calcium becomes deposited in the lesion (due to dystrophic calcification)
- fissuring, rupture or ulceration of the plaque may form cholesterol emboli (cholesterol can form crystals)
- treatment may involve anti-platelet or thrombolytic drugs
Consequences of plaque formation: Atherosclerotic Occlusions
- in small vessels, such as the coronary arteries and cerebral arteries, partial or total vascular occlusion may result
- > ischemia
Consequences of plaque formation: Atherosclerotic Aneurysms
-in large vessels, such as the aorta, the lumen doesn’t become occluded, but atherosclerotic aneurysms may develops
aneurysm definition
weakness or defect in arterial wall, pushed to the outside due to the increased blood pressure pushing it out of the way of the lumen
Consequences of plaque formation: Atherosclerotic Thrombi
- thrombi may form over the top of the lesion (these may form suddenly and cause infarction)
- called complicated lesions = atheroma + blood clot
- chronic lesion w/acute crisis
Clinical consequences of the location of atherosclerosis
- coronary arteries
- cerebral arteries
- renal arteries
- intestinal arteries
- atherosclerosis in the extremities
coronary arteries
major factor in the development of myocardial infarction
cerebral arteries
major factor in the development of stroke
renal arteries
hypoperfusion of the kidneys (not enough blood flow), reduced renal capacity and renin release, and leads to hypertension
intestinal arteries
- chronic ischemia causes nonspecific gastrointestinal problems
- acute occlusion causes massive intestinal infarction
Atherosclerosis in the extremities
- chronic ischemia: undwrperfusion of the leg muscles leading to cramps
- sudden occlusion of the arteries leads to gangrene
Players in the pathogenesis of atherosclerotic lesions
- chronic endothelial injury as an initiating agent (thrombogenic)
- hemodynamic disturbances (turbulent blood flow, atherosclerosis often found @ bifurcations)
- adverse effects of hypercholesterolemia
- smoking increases LDL oxidation
- Endothelial toxins
Endothelial toxins
- homocysteine
- marked increase in homocysteine after menopause
Systolic pressure
peak blood pressure which occurs during contraction of the ventricles
Diastolic pressure
minimum blood pressure which occurs as the heart rests between contractions
Normal BP
Systolic less than 120
Diastolic less than 80
Prehypertension BP
systolic 120-139
diastolic 80-89
Stage 1 hypertension
systolic 140-159
diastolic 90-99
Stage 2 hypertension
systolic greater than 160
diastolic grater than 100
Mean arterial Blood Pressure
MAP = diastolic pressure + 1/3 of the pulse pressure
diastolic + ((sys-diast)/3)
Pulse pressure
systolic pressure - diastolic pressure
