Heart and Blood Vessels

What are the three layers of a blood vessel?

Intima, Media, and Adventitia

What cells line the intima?

Endothelial cells

What are the main components of the vessel wall ECM?

Elastin, collagen, and glycosaminoglycans

What is the main function of the arterial media?

Provides strength and regulates vessel tone through smooth muscle contraction

What supplies blood to the outer media and adventitia?

Vasa vasorum

What is contained within the adventitia?

Connective tissue, nerve fibers, and vasa vasorum

Which vessels are the most important for blood pressure control?

Arterioles

What is the main function of capillaries?

Diffusion and exchange of substances

Where does most vascular leak and leukocyte adhesion occur during inflammation?

Post-capillary venules

What proportion of the body's blood volume is contained in veins?

Approximately two-thirds

What is vasculogenesis?

Formation of blood vessels during embryonic development

Which growth factor is essential for vasculogenesis?

VEGF

What is angiogenesis?

Formation of new blood vessels in adulthood

What is arteriogenesis?

Remodeling and adaptation of arteries to chronic changes in flow or pressure

What is a major function of healthy endothelial cells?

Maintaining a non-thrombogenic surface

What important clotting protein is stored in endothelial cells?

von Willebrand factor

What molecule do endothelial cells release to cause vasodilation?

Nitric oxide (NO)

What molecule is released during hypotension to promote vasoconstriction?

Endothelin-1

What is endothelial dysfunction?

An altered endothelial phenotype characterized by impaired vasoreactivity and increased thrombosis

What diseases are associated with endothelial dysfunction?

Atherosclerosis, thrombosis, and hypertensive vascular disease

What functions do vascular smooth muscle cells (VSMCs) perform?

Control vessel tone, proliferate, and produce ECM

Which growth factor stimulates VSMC proliferation?

PDGF

Which molecule inhibits VSMC proliferation?

Nitric oxide

What causes intimal thickening?

Endothelial injury causing VSMC proliferation and ECM deposition

What is neointimal hyperplasia?

Proliferation of VSMCs within the intima after injury

How does arteriosclerosis affect the vessel lumen?

It progressively narrows and may completely occlude the lumen

What blood pressure defines hypertension in these notes?

139 mmHg systolic or >89 mmHg diastolic

Why is hypertension called the silent killer?

It often remains asymptomatic until complications occur

Name four complications of hypertension.

Atherosclerosis, renal disease, heart failure, and aortic dissection

What determines blood pressure?

Cardiac output (CO) and total peripheral resistance (TPR)

How does increased sodium affect blood pressure?

Increases blood volume and therefore blood pressure

What are major vasoconstrictors involved in blood pressure regulation?

Angiotensin II, endothelin, and adrenaline

What are major vasodilators involved in blood pressure regulation?

Nitric oxide and prostacyclin

What hormone initiates the RAAS pathway?

Renin

Where is renin produced?

Juxtaglomerular cells of the kidney

What converts angiotensin I into angiotensin II?

Angiotensin-converting enzyme (ACE)

What are the effects of angiotensin II?

Vasoconstriction and stimulation of aldosterone release

What does aldosterone do?

Increases sodium and water reabsorption

What syndrome involves increased ENaC activity causing hypertension?

Liddle syndrome

What is secondary hypertension?

Hypertension caused by an identifiable underlying condition

What causes renovascular hypertension?

Renal artery obstruction reducing kidney perfusion

What is hyaline arteriosclerosis?

Protein leakage and ECM deposition in vessel walls

What is hyperplastic arteriosclerosis?

Concentric smooth muscle thickening associated with severe hypertension

What does arteriosclerosis mean?

Hardening of the arteries

What is Mönckeberg medial sclerosis?

Calcification of muscular arteries without significant luminal obstruction

What is the most clinically important form of arteriosclerosis?

Atherosclerosis

Why do premenopausal women have lower atherosclerosis risk?

Vasoprotective effects of estrogen

Name four modifiable risk factors for atherosclerosis.

Hyperlipidemia, hypertension, smoking, and diabetes

Which lipoprotein is most strongly associated with atherosclerosis?

LDL

What is the role of HDL?

Transports cholesterol from tissues to the liver

How do omega-3 fatty acids affect LDL levels?

They decrease LDL

What effect does exercise have on HDL?

It increases HDL

How does cigarette smoking affect cardiovascular risk?

It approximately doubles the risk

How does diabetes contribute to atherosclerosis?

Causes endothelial damage and hypercholesterolemia

What are the three theories of atherogenesis?

Response to injury, response to retention, and oxidative modification hypothesis

What is the initiating event in the response-to-injury hypothesis?

Endothelial injury or dysfunction

Which areas are particularly susceptible to endothelial injury?

Arterial bifurcations and sites of turbulent flow

What cell type becomes a foam cell?

A macrophage that has ingested oxidized LDL

What adhesion molecule helps monocytes enter developing plaques?

VCAM-1

What cytokine released by macrophages promotes inflammation in plaques?

TNF-alpha

What forms the necrotic core of an atherosclerotic plaque?

Dead foam cells, lipids, and cellular debris

At what arterial occlusion does exertional angina commonly occur?

Approximately 70% occlusion

What events can lead to acute thrombosis of a plaque?

Erosion, rupture, or hemorrhage

What is a vulnerable plaque?

An inflamed plaque prone to rupture

Why do heart attacks commonly occur between 6 am and midday?

Blood pressure is higher, increasing shear stress on plaques

What is an aneurysm?

A localized abnormal dilation of a blood vessel or heart wall

What is a dissection?

Blood entering the vessel wall and separating its layers

What genetic disorder commonly predisposes to aneurysm formation?

Marfan syndrome

What protein is defective in Marfan syndrome?

Fibrillin

What are the two most important causes of aneurysms?

Atherosclerosis and hypertension

Which type of aneurysm is most commonly caused by atherosclerosis?

Abdominal aortic aneurysm (AAA)

Which group is most likely to develop AAA?

Male smokers over 50 years old

What enzyme family contributes to aneurysm formation by degrading ECM?

Matrix metalloproteinases (MMPs)

What is the major risk factor for aortic dissection?

Hypertension

What vessel layer is primarily weakened in aortic dissection?

The media

What symptom strongly suggests aortic dissection?

Sudden severe chest pain that radiates downward

What is the most common cause of death in aortic dissection?

Rupture leading to massive hemorrhage

What is vasculitis?

Inflammation of blood vessel walls

What are common systemic symptoms of vasculitis?

Fever, malaise, myalgia, and arthralgia

How much blood does the heart pump each day?

About 6000 liters

Which ventricle has the thicker wall?

Left ventricle

What hormone is released by stretched atrial myocytes?

Atrial natriuretic peptide (ANP)

What structures electrically connect cardiac myocytes?

Gap junctions within intercalated discs

Name the four heart valves.

Aortic, pulmonary, mitral, and tricuspid

What is the normal cardiac pacemaker?

The sinoatrial (SA) node

Describe the normal cardiac conduction pathway.

SA node → AV node → Bundle of His → Bundle branches → Purkinje fibers

When does coronary blood flow primarily occur?

During diastole

What are the three major coronary arteries?

LAD, LCX, and RCA

What is ischemic heart disease (IHD)?

Myocardial ischemia caused by inadequate blood supply

What percentage of IHD cases are caused by coronary atherosclerosis?

Approximately 90%

What degree of coronary stenosis typically produces exertional angina?

More than 75%

What degree of stenosis typically produces angina at rest?

More than 90%

What are the three major contributors to IHD pathogenesis?

Atherosclerosis, thrombosis, and vasospasm

What is stable angina?

Chest pain during exertion due to fixed coronary stenosis

What is unstable angina?

Chest pain occurring at rest or with less activity due to plaque disruption

What is Prinzmetal angina?

Angina caused by coronary vasospasm

What is a myocardial infarction?

Death of myocardial tissue due to ischemia

What is the most common cause of MI?

Rupture of an atherosclerotic plaque with thrombus formation

How long is myocardial injury potentially reversible after ischemia begins?

Approximately 20 minutes

What is the gold-standard biochemical marker for MI?

Troponin T or Troponin I