Cardiovascular

Cardiovascular System: Normal Structure and Function
Blood flow through the heart
• Deoxygenated blood from the systemic circulation returns through the superior and inferior venae cavae to the right atrium. Blood from the heart muscle itself also drains into the right atrium through the coronary sinus.
• Blood flows from the right atrium through the tricuspid (right atrioventricular) valve into the right ventricle.
• When the right ventricle contracts, blood passes through the pulmonary semilunar valve into the pulmonary trunk and pulmonary arteries, which carry it to the lungs.
• In the lungs, blood releases carbon dioxide and takes up oxygen. Oxygenated blood returns to the left atrium through the pulmonary veins.
• Blood flows through the mitral (bicuspid or left atrioventricular) valve into the left ventricle.
• When the left ventricle contracts, blood passes through the aortic semilunar valve into the aorta and is distributed through the systemic circulation.
• Arteries carry blood away from the heart; veins return blood to the heart. The terms refer to direction of flow, not oxygen content.
Circulatory circuits and perfusion
• The right side of the heart pumps blood to the lungs; the left side pumps blood through the systemic circulation. The left ventricle must generate greater pressure because it supplies the entire body.
• The pulmonary circuit is a low-pressure, low-resistance circuit; the slide lists flow at 5 liters/min, pressure at 25/8 mmHg, and mean arterial pressure (MAP) at 14.
• The systemic circuit is a higher-pressure, higher-resistance circuit; the slide lists flow at 5 liters/min, pressure at 120/80 mmHg, and MAP at 93.
• Perfusion means blood flow through an organ’s capillaries, sufficient to support normal cellular function and homeostasis.
• Effective perfusion depends on a healthy pump (the heart), healthy blood vessels, and adequate blood volume to create pressure gradients.
Atherosclerosis and Coronary Artery Disease
Effects on arteries and blood flow
• Atherosclerosis involves deposition of fatty and fibrous material in arterial walls. The material can harden over time, reduce vessel compliance, narrow the lumen, reduce tissue blood flow, and increase resistance and cardiac workload.
• Lumen: the open space within a blood vessel through which blood flows.
• Occlusion: narrowing or blockage of a vessel lumen; it can be partial or complete.
• Compliance: a vessel’s ability to stretch and recoil. Atherosclerotic lesions reduce compliance at the affected site.
• Ischemia: inadequate blood flow to a tissue. If ischemia is prolonged and tissue dies, the result is necrosis; in the heart, this is a myocardial infarction (heart attack).
• Atherosclerosis can affect coronary, cerebral, and other arteries. Cerebral atherosclerosis has been discussed as a contributing factor associated with Alzheimer’s disease dementia, not necessarily as its sole cause.
Arterial wall structure
• The tunica intima is the innermost layer; its endothelial lining contacts the blood.
• The tunica media is the middle layer, composed primarily of smooth muscle that can change vessel diameter.
• The tunica adventitia is the outer connective-tissue layer.
• An atheroma is the site of an atherosclerotic lesion in the arterial wall.
Plaque development
1. Endothelial damage or dysfunction is described as an early initiating event in atherosclerosis.
2. Excess LDL particles can enter the arterial wall, particularly the tunica intima and underlying tissue. LDL carries cholesterol from the liver to peripheral tissues.
3. LDL can become oxidized or otherwise modified. Immune cells are recruited to the area, including monocytes that enter tissue and become macrophages.
4. Macrophages engulf modified LDL. When overloaded with lipid, they appear foamy and are called foam cells. Their accumulation forms an early fatty streak.
5. In a more advanced lesion, inflammatory signals stimulate smooth muscle cells to proliferate and migrate, forming a fibrous cap over the plaque. A fibrous plaque can narrow the lumen while remaining relatively stable.
6. In a complicated lesion, inflammation and tissue damage can weaken or rupture the plaque surface. Blood then contacts underlying tissue, triggering clot formation. A clot can rapidly produce complete occlusion.
7. If a coronary artery becomes completely blocked, downstream heart muscle loses its blood supply. Prolonged ischemia can cause tissue death and a heart attack.
“The earliest initiating events in starting your discussion on atherosclerosis is the damaged endothelium.”
Coronary artery disease
• Coronary artery atherosclerosis can occur at one or multiple sites, and lesions vary in length and severity.
• The lecture showed an angiographic example with a 99% blockage in the left anterior descending artery and an 80% blockage farther along it. The left anterior descending artery supplies a major portion of the left ventricle.
• Reduced coronary blood flow can cause chest pain, especially when the heart’s oxygen demand rises during activity.
Atherosclerosis Risk Factors and Biomarkers
Risk factors
• Non-modifiable risk factors listed in the notes: age, gender, family history, and race.
• Modifiable risk factors listed in the notes:
• High LDL (“bad cholesterol”) and low HDL (“good cholesterol”).
• Hypertension.
• Cigarette smoking.
• Elevated C-reactive protein (CRP), as a marker associated with inflammation.
• Risk factors increase likelihood; they do not guarantee that a cardiovascular event will occur. The lecture discussed lifestyle changes, medication, and surgical intervention as possible ways to reduce risk.
Cholesterol
• LDL (low-density lipoprotein) transports cholesterol to peripheral tissues. Chronically elevated LDL is associated with greater atherosclerosis and cardiovascular risk.
• HDL (high-density lipoprotein) supports reverse cholesterol transport. Higher HDL is generally considered a more favorable profile.
• Dyslipidemia refers to an unfavorable lipid profile, such as high LDL and low HDL.
• The lecture described longitudinal studies, including the Framingham studies, as evidence associating higher cholesterol and lower HDL with cardiovascular complications. It also emphasized that heart attacks can occur in people without an unfavorable cholesterol profile.
• Dietary approaches discussed included reducing saturated fat and emphasizing fruits and vegetables.
C-reactive protein
• CRP is produced by the liver in response to inflammation and can be measured with a blood test.
• Inflammation-related signals, including interleukin-6 (IL-6), can stimulate liver production of CRP.
• Chronically elevated CRP may indicate inflammation somewhere in the body; it is not specific to atherosclerosis.
• The lecture described CRP and cholesterol as complementary risk markers: people with unfavorable cholesterol and high CRP were presented as having the greatest risk of a coronary event, while favorable levels of both were associated with lower risk.
Hypertension
Blood pressure categories
• The lecture emphasized that, according to the cited guidelines, normal blood pressure is less than 120 systolic and less than 80 diastolic.
• The JNC 7 table in the notes lists:
• Normal: systolic <120 and diastolic <80.
• Elevated: systolic 120–129 and diastolic <80.
• Stage 1: systolic 130–139 or diastolic 80–89.
• Stage 2: systolic >140 or diastolic >90.
• The lecture used consistent readings of 119/79 as normal and 130/87 as not normal under this chart.
• The notes cite the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7, 2003).
Causes and consequences
• Primary (essential) hypertension is idiopathic: no specific underlying cause is identified in most cases.
• Secondary hypertension results from an underlying condition. The lecture estimated that about 10% of cases are secondary and mentioned endocrine causes involving cortisol, thyroid hormone, aldosterone, or adrenaline, as well as potentially treatable underlying disease.
• Hypertension can injure the endothelium and contribute to atherosclerosis. It may go unnoticed for a long time, making blood-pressure measurement important.
• Blood pressure is related to blood volume: reducing volume can lower pressure, while increasing volume can raise it.
Drug treatments
• Diuretics reduce blood volume.
• Beta-blockers reduce heart rate and contractility, decreasing cardiac workload.
• Vasodilators relax arteries and reduce constriction.
• Calcium channel blockers and ACE inhibitors are among the drug classes discussed.
• The renin–angiotensin pathway:
1. When the kidneys detect low blood pressure or volume, they release renin.
2. Renin converts angiotensinogen to angiotensin I.
3. Angiotensin-converting enzyme (ACE) converts angiotensin I to angiotensin II.
4. Angiotensin II binds receptors on vascular smooth muscle and promotes vasoconstriction, which raises blood pressure.
5. ACE inhibitors reduce angiotensin II production; angiotensin II receptor blockers prevent angiotensin II from exerting its receptor-mediated effects.
Lifestyle and device-based approaches
• The DASH diet (Dietary Approaches to Stop Hypertension) was described as emphasizing fruits and vegetables and reducing salt and fat.
• Exercise and dietary changes were discussed alongside pharmacological treatment as ways to address hypertension.
• Carotid baroreceptors detect changes related to blood pressure and signal the brain. When stimulated by high pressure, they can lead to reduced sympathetic nervous system activity.
• The lecture also described a baroreceptor-stimulation device as a biotechnology-based treatment approach, noting its FDA approval and clinical availability at the time of the lecture.
Course and Reference Context
• The material is from Unit 3: Cardiovascular Pathophysiology, with McCance & Huether Chapters 31 and 32 listed in the notes.
• The slides cite Taubes, Science, volume 296, pages 242–245 (2002); Scientific American (2002), “Atherosclerosis: The New View”; JNC 7 (2003); and an article on intracranial atherosclerosis and Alzheimer’s disease dementia in Alzheimer’s & Dementia (2011).