Lecture 6 Pathophysiology

Blood Vessel Diseases

• This lecture covers blood vessel diseases, focusing on atherosclerosis, hypertensive vascular disease, and Mönckeberg medial sclerosis.
• The lecture discusses the structure and function of blood vessels, along with their response to injury.
• It also delves into the pathogenesis, epidemiology, and clinical consequences of each disease.

Structure and Function of Blood Vessels

• Blood vessels have regional specializations in structure and function.
• Different types of blood vessels (e.g., arteries, veins, arterioles, venules) have unique layers (intima, media, adventitia; elastic lamina).
• Arteries are responsible for high-pressure blood flow, characterized by muscular layers mediating vasoconstriction/dilation.
• Veins transport low-pressure blood back to the heart, with larger lumens for easier flow.
• Arterioles regulate blood flow to capillary beds.
• Blood pressure is controlled and regulated in the arterioles, which allow for vasodilation or vasoconstriction.

Vascular Wall Response to Injury

• Intimal thickening is a common response to vessel wall injury, regardless of specific cause.
• Injury prompts smooth muscle cell proliferation, extracellular matrix production, and inflammation.
• Smooth muscle cells migrate from the outer layer of the vessel into the inner tunic (intima), causing thickening and potentially disrupting normal blood flow.
• Multiple causes of injury include infection, inflammation, immune responses, and exposure to toxic substances (e.g., oxidized lipids from cigarette smoke).
• Neointimal smooth muscle cells exhibit characteristics different from medial smooth muscle cells, with a greater capacity for division and synthesis.

Arteriosclerosis

• Arteriosclerosis refers to hardening of the arteries, a general term for thickening of arterial walls and loss of elasticity.
• Three types are commonly recognized: hypertensive arteriosclerosis, atherosclerosis, and Mönckeberg medial calcific sclerosis.
• Hypertensive arteriosclerosis affects small arteries and arterioles and may cause downstream ischemic injury. It is associated with hypertension and includes variants like hyaline and hyperplastic arteriolosclerosis. Two variants have been described in relation to hypertension.
• Atherosclerosis is the most frequent and clinically significant type of arteriosclerosis, characterized by the presence of atherosclerotic plaques within the vessel intima.
• These plaques consist of a fibrous cap, a necrotic center, and varying amounts of lipid, both inside and outside cells.
• Mönckeberg medial calcific sclerosis involves calcification of the media of medium and small muscular arteries, typically in older adults, but is usually not clinically significant. Microscopic images illustrating these features are available in the lecture slides.

Hypertensive Vascular Disease

• Essential/primary hypertension (95%): Causes are generally unknown, with genetic predispositions and environmental factors contributing.
• Genetic polymorphisms in angiotensinogen and angiotensin II receptor genes and environmental factors (stress, obesity, smoking, inactivity, high salt consumption) interplay in blood pressure regulation.
• Blood volume, hormonal factors (e.g., angiotensin II, natriuretic peptides), cardiac output, peripheral resistance (regulated by arteriolar smooth muscle), and neural/local factors directly influence blood pressure.
• Secondary hypertension arises due to specific medical conditions, including chronic renal disease, renal artery stenosis, adrenal disorders (like primary hyperaldosteronism, Cushing syndrome, pheochromocytoma), and renin-secreting tumors.
• Hypertensive vascular disease is characterized by changes in smaller blood vessels, like hyalinoic arteriolosclerosis or hyperplastic arteriolosclerosis.

Atherosclerosis

• Atherosclerosis is the presence of atheromatous/atherosclerotic plaques in the arterial intima.
• The plaques feature a fibrous cap, necrotic center, and lipid components (both intracellular and extracellular).
• Atherosclerosis epidemiology shows higher prevalence in developed nations and is a significant cause of death globally, particularly due to ischemic heart disease (IHD).
• Risk factors include nonmodifiable factors like genetics, age, and gender, and modifiable ones such as hypertension, hyperlipidemia, smoking, diabetes, and inflammation.
• Risk factors can interact multiplicatively such that possessing multiple factors elevates the risk even more than simply adding the risks together.
• Pathogenesis follows the response-to-injury hypothesis, characterized by endothelial injury, intimal cellular proliferation, repeated thrombus formation, and various risk factors.
• Clinical consequences include a diverse array of complications, such as angina, myocardial infarction, stroke, peripheral artery disease, aneurysms, and renal artery stenosis.
• Unstable plaques are more susceptible to rupture, promoting thrombus formation, which can lead to potentially fatal consequences like ischemic events. Stable plaques, on the other hand, have a thicker fibrous cap and less risk of rupture.

Competencies

• Pharmacy students should understand the pathophysiological mechanisms of blood vessel diseases, use relevant medical terminology, integrate fundamental science concepts with clinical manifestations, comprehend the role of physicians within a comprehensive healthcare team, and link disease characteristics to appropriate drug treatment strategies.
• The lecture emphasizes the importance of recognizing risk factors and preventing cardiovascular complications.