CVD: Blood Circulation and Atherosclerosis Flashcards
How is deoxagenated and oxygenated blood circulated?
- The right atrium receives deoxygenated blood from the systemic circulation. The two major systemic veins, the superior and inferior venae cavae, empty into the right atrium. The superior vena cava drains blood from regions above the diaphragm and the inferior vena cava drains blood from areas below the diaphragm.
- The right ventricle receives blood from the right atrium through the tricuspid valve, a valve found in the opening of the atrioventricular septum. When the right ventricle contracts, the pressure within the ventricular chamber increases causing the blood to flow toward the pulmonary trunk and the right atrium. The tricuspid valve closes to prevent any potential backflow into the right atrium.
- The Left atrium receives oxygenated blood via four pulmonary veins. Most of the filling occurs while the atria are relaxed.
- The left ventricle receives blood from the left atrium through the bicuspid (mitral) valve which is situated in the opening of the atrioventricular septum. The left ventricle ejects blood into the aorta through the aortic semilunar valve.
What are the heart muscle layers?
muscle layers epicardium, myocardium, endocardium
Conduction system of the heart
Parts of the ECG
The major points on the ECG are the P wave, the QRS complex, and the T wave.
* The small P wave represents the depolarization of the atria.
* The large QRS complex represents the depolarization of the ventricles, a stronger electrical signal because of the larger size of the ventricular cardiac muscle.
* The T wave represents repolarization of the ventricles. Atrial repolarization occurs during the QRS complex but is masked.
Action potential in cardiac myocytes
- Myocardial cells are activated
- rapid depolarization of cells through ion channels with influx of Na+
- plateau follows with Na+ channels closing and slow Ca2+ channels open
- repolarzaiton follows with slow Ca2+ channels closing
- During the refractory period, myocytes cannot be stimulated in this time frame until things come back to the original state
How does action potential differ between skeletal muslce and cardiac muscle?
Differ in activation potential and contraction.
* action potential and contraction is strong and brief for skeletal so can be contracted repeatedly.
How does parasympathetic and sympathetic autonomic innervation effect the heart?
- parasympathetic stimulation (vagus nerve) → decreases heart rate with hyperpolarization and slower depolarization
- sympathetic stimulation (sympathetic cardiac nerve) → increase heart and rate and force of contraction with reduced repolarization and faster depolarization
Systemic blood pressure
Pressure goes down as we get away from the heart.
Why is glucose more damaging in smaller vessels?
- Capillleries damaged by glucose are more subjected to glucose because it can cause changes with membrane proteins.
- With aorta, the effect of glucose is less important it has a lot more area and elasticity and can deal with greater pressures
pathophysiology of hypertension
Notes
* See inflammation in bigger blood vessels
* RAAS regulates blood pressure
* Insulin resistance can be induced by FAs but they also damage vessels
What are cardiovascular diseases?
A family of diseases that affect the heart and (bigger) blood vessels
* Main causes are atherosclerosis and hypertension
CVD association with FAs vs. glucose
- Associated with atherogenic dyslipidemia: high TG, increased LDL particles, and low HDL particles
- The link with glucose is not strong. It implicates a vast array of other metabolic factors (inflammation, adipokines/cytokines, fatty acids)
Association between TG and CVD
TG is consdiered a silver bullet and one of the best predictors of heart disease
* more significant in women
* a strong predictor of CVD
* TG levels increase with age
What are the 2 main causes of CVD?
BP and atherosclerosis
What are some underlying mechanisms causing CVD?
- Aging of irreplaceable elastin
- Oxidation and cross linking of collagen and elastin
- Accumulation of lipids and activated macrophages in blood vessels.
What does an artery with atherosclerosis look like?
Cholesterol and lipoproteins bind to the arterial wall getting into the intima, and expand the wall outwards into the lumen. Macrophages try to eat the fat and other debris causing it to grow becoming a foam cell, which is then trapped and cannot leave. Macrophages also secrete cytokines and other immmune cells such as monocytes and T cells which contribute further to plaque build up. As it grows bigger the core of the plaque no longer receives nutrients or oxygen supplies. Cellular debris forms and necrosis
How does a narrowing of the blood vessel occur?
fatty streaks develop with lipid droplet attachment to arterial wall followed by accumulation of fats in the wall and plaque build up which grows into the lumen narrowing the vessel and restricting flow causing stenosis
How does thrombosis occur?
- lesion iniation: more LDL particles in circulation have greater potential to bind walls (can also be oxidized and cause damage) and once inside macrophages try to clear LDL and secrete cytokines forming foam cells
- fatty streak: appear when the presence of foam cells at the site of plaque formation expands with a progressive lipid core secreting cytokines and growth factors which activated the endothelium and attack to smooth muslce cells (proliferation)
- fibrous plaque: presence of foam cell, with smooth muscle cell mitigation to the endothelium building up a wall rich in SMC and and collagen. neovascularization occurs and platelets get activated.
- thrombosis: cell debris ruptures, the lipid core becomes necrotic, the endothelium bursts released a thrombus (blood clot) and get more plateletal activated and can travel to a distal site getting stuck and clotting it.
What are the important layers of the vessel walls?
- endothelium
- intima
- elastic lamina interna
- media
Macroscopic changes associated with Atherosclerosis
- vasoconstriction
- VSMC migration (vasoconstriction)
- inflammation
- cytokines (creates inflammation)
- adhesion molecules
- thrombosis
- hypercoagulation
- platelet activation
- decreased fibrinolysis
- endothelial dysfunction
- macrophage phenotype
What suggests we are hardwired to develop atherosclerosis?
atherosclerosis in ancient populations from distinct populations including pre-agricultural and hunters/ gatherers (ancient egyptians, peruvians, ancestral puebloans, unangans) which are subjected to CT scans to visualized calcified plaques and signs of atherosclerosis were discovered in 34% of the mummies
What did athersclerosis correlated with in anciet populations?
atherosclerosis correlates with age at time of death
* increase of plaque formating with age
What were the lives of ancient populations like and what conclusion can be drawn from this?
Concluded that main driver for athersclerosis was age. They had different diets and lifestyles and only variable of association was age.
* The presence of atherosclerosis in ancient human populations raises the possibility of a basic predisposition to the disease
* The severity raises with age suggesting it could be inherent to human ageing
