patho quiz 4 hypertension and atherosclerosis.txt

• Endothelial cells (ECs)
• Smooth muscle cells (SMCs)
• Extracellular matrix (ECM)

• Intima
• Media
• Adventitia

• Single layer of ECs
• Underlaying dense elastic membrane (internal elastic lamina) consisting of ECM

• Layers of SMCs and connective ECM
• The outer limit of the media is defined by the external elastic lamina consisting of ECM

• Connective tissue
• Nerve Fibers
• Vasa vasorum

Cells of this layer receive nutrients and oxygen from pores in internal elastic lamina (fenestrations) and from small arterioles that originate from outside the vessel and reside in the adventitia (vasa vasorum)

carry oxygenated, nutrient-rich blood to tissues

responsible for diffusion exchange of nutrients, oxygen, and waste between blood and tissues

Carry deoxygenated blood to lungs

• Include the aorta and its large branches (innominate, subclavian, common carotid, and iliac)
• The elastic, fiber rich media layer of these vessels expands during systole and recoils during diastole. This propels blood through the peripheral vasculature
• These vessels can be affected by atherosclerosis

• Include other brances of the aorta, such as the coronary and renal arteries
• Rich in SMCs and regulates blood flow and blood pressure by vasoconstriction and vasodilation
• These vessels can be affected by atherosclerosis

• Lie within organs and tissues
• The media layer of these vessels is rich in SMCs and regulates blood flow and blood pressure by vasoconstriction and vasodilation
• The arterioles are principal points for regulating blood pressure and velocity and for changing pulsatile flow and steady flow

• They are approximately the diameter of a RBC (7-8micrometers)
• They consist of an endothelial cell lining but no media layer
• Their thin walls and slow blood flow make them ideal for diffusion exchange between blood and tissues

larger, larger, thinner

• Irregular dilation (varicose veins)  varices
• Compression  restricted blood flow
• Penetration by tumors  tumor metastatsis
• Damage by inflammatory processes  thrombophlebitis

• Coronary heart disease
• Cerebrovascular accidents
• Cardiac hypertrophy and subsequent heart failure
• Aortic dissection
• Renal failure

• Blood volume (Na homeostasis)/cardiac output
• Peripheral resistance (vasodilation/constriction of arterioles)
• Kidneys (regulate bp in two ways)

Renin converts angiotensin to angiotensin 1. ACE then converst ANG1 to ANG2. ANG2 is responsible for vasoconstriction and aldosterone secretion (signals NA reabsorption)

controls the amount of Na reabsorbed

• Genetic factors  possibly due to combinations of mutations or polymorphisms that cooperate to result in HTN
• Reduced renal Na secretion  causes increased blood volume needed to maintain Na homeostasis
• Vasoconstrictive influences
• Stress (vasoconstrictive factors; epinephrine)
• Smoking (vasoconstrictive; nicotine)
• Obesity (increase in capillary bed size)
• Excessive salt consumption (increase blood volume)

Atherosclerosis is characterized by fibrofatty deposits or plaques that protrude into or obstruct the vascular lumina. It contributes to approximately half of all deaths in the western world.

• Myocardial infarction (heart attack)
• Cerebral infarction (stroke)
• Aortic aneurisms
• Peripheral vascular disease (gangrene of the legs)
• Ischemic injury

directly impairs EC function through increased production of Oxygen Free Radicals

• Familial (genetic) predisposition (hyperlipidemia)
• Hyperlipidemia/ hypercholesterolemia (lifestyle)
• Hypertension
• Cigarette smoking
• Diabetes
• Stress

physical injury to EC

circulating constituents of smoke cause EC damage

chemical/inflammatory injury

disruptions of laminar flow contribute to monocyte and platelet adhesion to endothelial cells

Chronic endothelial injury �!endothelial dysfunction; monocyte adhesion and migration �! macrophage activation; smooth muscle recruitment �! Macrophage and smooth muscle cells engulf lipid �! smooth muscle proliferation, collagen and other ECM deposition, extracellular lipid

• Increased vascular permeability
• Leukocyte and monocyte adhesion, emigration (into the lamina), and transformation into macrophages  causing swelling of intima
• Insudation (integration and invasion) of liproproteins into the vessel wall and the intima and subsequent oxidation of these lipids
• 1. Stimulates monocyte accumulation in intima (chemoattractant)
• 2. Is cytotixic to ECs and can induce EC dysfunction
• Platelet adhesion and activation
• Activation of platelets and macrophages and release of factos that promote SMC emigration

• EC injury and dysfunction
• SMC emigrate from media to intima- this is accompanied by SMC proliferation and SMC synthesis and secretion of ECM components, resulting in accumulation of collagen and proteoglycans in intima and intima swelling
• Oxidized lipids accumulate within macrophages and SMCs
• oThis stimulates the release of growth factors and cytokines by macrophages and SMCs
• oThis is cytotoxic to SMCs- causing inflammation as body attempts to clear dying SMCs