Blood Vessels. Dr. Nabila Hamdi MD, PhD

Transcription

1 Blood Vessels Dr. Nabila Hamdi MD, PhD

2 ILOs Understand the structure and function of blood vessels. Discuss the different mechanisms of blood pressure regulation. Compare and contrast the following types of hypertension: benign, malignant, essential and secondary. Discuss the morphologic effects of hypertension on different organs and enumerate their clinical consequences. Compare and contrast between hyaline and hyperplastic arteriosclerosis in terms of pathogenesis, morphology and clinical significance. Differentiate between arteriosclerosis, atherosclerosis and Mönckeberg medial sclerosis. Be aware of the risk factors of atherosclerosis Outline the development of the atherosclerotic lesion with respect to: pathogenic mechanisms morphology clinical manifestations complications

3 Outline I. STRUCTURE AND FUNCTION OF BLOOD VESSELS II. VASCULAR WALL RESPONSE TO INJURY III. BLOOD PRESSURE REGULATION IV. ARTERIOSCLEROSIS HYPERTENSIVE VASCULAR DISEASE Pathogenesis of Hypertension Vascular Pathology in Hypertension MONCKEBERG MEDIAL SCLEROSIS ATHEROSCLEROSIS Epidemiology Pathogenesis Morphology Clinical Consequences 3

4 STRUCTURE AND FUNCTION OF BLOOD VESSELS Regional vascular specializations Elastic arteries Iliac, pulmonary Expansion/recoiling Coronary, renal Vasoconstriction/ Vasodilation Arterioles are where blood flow resistance is regulated 4

5 STRUCTURE AND FUNCTION OF BLOOD VESSELS Endothelial Cell Properties and Functions Injury or exposure to certain mediators results in endothelial activation, a state in which endothelial cells have adhesive, procoagulant surfaces and release factors that lead to smooth muscle contraction and/or proliferation and matrix synthesis. 5

6 STRUCTURE AND FUNCTION OF BLOOD VESSELS Vascular Smooth Muscle Cells Participate in both normal vascular repair and pathologic processes such as atherosclerosis. When stimulated by various factors, SMC can: proliferate upregulate ECM collagen, elastin, and proteoglycan production elaborate growth factors and cytokines. SMC also mediate the vasoconstriction or vasodilation that occurs in response to physiologic or pharmacologic stimuli. 6

7 VASCULAR WALL RESPONSE TO INJURY Thrombosis Atherosclerosis Hypertensive vascular disease Intimal Thickening: A stereotypical response of the vessel wall to any insult. Infection, inflammation, immune injury, physical trauma (e.g., from a balloon catheter or hypertension), or toxic exposure (e.g. oxidized lipids or cigarette smoke) Neointimal smooth muscle cells lack the capacity to contract like medial smooth muscle cells, but do have the capacity to divide and have a considerably greater synthetic capacity than their medial colleagues. 7

8 ARTERIOSCLEROSIS Arteriosclerosis literally means hardening of the arteries It is a generic term reflecting arterial wall thickening and loss of elasticity. Three distinct types are recognized, each with different clinical and pathologic consequences: Hypertensive vascular disease: affects small arteries and arterioles and may cause downstream ischemic injury. Two variants, hyaline and hyperplastic arteriolosclerosis are described in relation to hypertension. Mönckeberg medial sclerosis is characterized by the presence of calcific deposits in muscular arteries, typically in persons older than 50. The lesions do not encroach on the vessel lumen and usually are not clinically significant. Atherosclerosis is the most frequent and clinically important pattern. 8

9 BLOOD PRESSURE REGULATION 9

10 BLOOD PRESSURE REGULATION Renin-producing tumors Aldosterone-secreting adrenal tumors (adrenal cortex) Natremia/Kalemia?? 10

11 HYPERTENSIVE VASCULAR DISEASE Essential hypertension results from the interplay of genetic polymorphisms and environmental factors. Sustained diastolic pressures greater than 90 mmhg, or sustained systolic pressures greater than 140 mmhg are used as cutoffs in diagnosing hypertension in clinical practice. Without appropriate treatment, 50% of hypertensive patients die of ischemic heart disease (IHD) or congestive heart failure, and another third succumb to stroke. Detection and treatment of asymptomatic hypertension constitute one of the few instances in which preventive medicine has a major demonstrated health benefit. 11

12 HYPERTENSIVE VASCULAR DISEASE Pathogenesis: The mechanisms leading to hypertension in the vast majority of affected persons remain unknown. Essential hypertension (idiopathic) (95%). Secondary hypertension: most cases are due to Primary renal disease (acute glomerulonephritis, chronic renal disease) Renal artery narrowing (Renal artery stenosis) (renovascular hypertension) Renin-producing tumors Adrenocortical hyperfunction (primary aldosteronism, Cushing syndrome) Pheochromocytoma Single-gene disorders (rare) cause hypertension by affecting renal sodium resorption (enzymes involved in aldosterone metabolism or proteins that affect sodium resorption) 12

13 HYPERTENSIVE VASCULAR DISEASE Reduced renal sodium excretion Increase in fluid volume Vasoconstriction/Structural changes In vessel walls Increased cardiac output Increased vascular resistance Essential Hypertension Genetic factors Angiotensinogen polymorphisms and angiotensin II receptor variants Environmental factors Stress, obesity, smoking, physical inactivity, and high levels of salt consumption 13

14 HYPERTENSIVE VASCULAR DISEASE Although it occasionally manifests in an acute aggressive form, high blood pressure is much more often asymptomatic for many years (Benign hypertension). Hypertension increases the risk of: Stroke Multi-infarct dementia Atherosclerotic coronary heart disease Cardiac hypertrophy and heart failure (hypertensive heart disease) Aortic dissection Renal failure Malignant hypertension (5%): rapidly rising blood pressure (systolic over 200 mm Hg or diastolic over 120 mm Hg). It is associated with renal failure and retinal hemorrhages and, if untreated, leads to death in within 1 to 2 years. 14

15 HYPERTENSIVE VASCULAR DISEASE Morphology: Hypertension accelerates atherogenesis and causes degenerative changes in the walls of large and medium sized arteries that can lead to aortic dissection and cerebrovascular hemorrhage. Two forms of small blood vessel disease are hypertension-related: Hyaline arteriolosclerosis is associated with benign hypertension The lesions stem from leakage of plasma components across injured endothelial cells, into vessel walls and increased ECM production by smooth muscle cells in response to chronic hemodynamic stress. Ex: Nephrosclerosis in the kidneys (glomerular scarring). The same changes occur in elderly patients (normo- or hypertensive) and in diabetic microangiopathy (hyperglycemia-associated endothelial cell dysfunction) Hyperplastic arteriolosclerosis is more typical of severe (malignant) hypertension. The laminations consist of smooth muscle cells and thickened, and reduplicated basement membrane. In malignant hypertension these changes are accompanied by fibrinoid deposits and vessel wall necrosis (necrotizing arteriolitis), which are particularly prominent in the kidney. 15

16 HYPERTENSIVE VASCULAR DISEASE Morphology: Hyaline arteriolosclerosis Homogeneous, pink hyaline thickening of the arteriolar walls, with loss of underlying structural detail, and luminal narrowing. Hyperplastic arteriolosclerosis Onionskin, concentric, laminated thickening of arteriolar walls and luminal narrowing. 16

17 ATHEROSCLEROSIS Atherosclerosis is characterized by the presence of intimal lesions called atheromas (or atheromatous or atherosclerotic plaques). The basic structure of an atheromatous plaque 17

18 ATHEROSCLEROSIS Epidemiology: Atherosclerosis is virtually ubiquitous among most developed nations but is much less prevalent in Central and South America, Africa, and parts of Asia. In the Western world, roughly half of all deaths are attributed to atherosclerosis. Epidemiologic data related to atherosclerosis mortality typically reflect deaths caused by ischemic heart diseases (IHD) (one fourth of all deaths in the US). The mortality rate for IHD in the United States is among the highest in the world, approximately five times higher than that in Japan. The prevalence and severity of atherosclerosis and IHD have been correlated with a number of risk factors. The risk factors have roughly multiplicative effects. Thus, two factors increase the risk of myocardial infarction approximately four-fold, and three (hyperlipidemia, hypertension, and smoking), increase the rate by a factor of 7. 18

19 ATHEROSCLEROSIS Epidemiology: Risk factors 19

20 Pathogenesis: ATHEROSCLEROSIS Endothelial injury Intimal cellular proliferation ATH Repeated formation and organization of thrombi Risk factors Response-to-injury hypothesis Atherosclerosis is a chronic inflammatory response of the arterial wall to endothelial injury 20

21 Pathogenesis: Fatty streaks are composed of lipid-filled foamy macrophages but are only minimally raised and do not cause any significant flow disturbance oxldl 21

22 ATHEROSCLEROSIS Morphology: Atherosclerotic plaques have three principal components: (1) Cells, including smooth muscle cells, macrophages, and T cells (2) Extracellular matrix, including collagen, elastic fibers, and proteoglycans (3) Intracellular and extracellular lipids Atherosclerotic plaque in the coronary artery (F): fibrous cap (C): central necrotic core (largely lipid) (L): lumen is moderately narrowed by this eccentric lesion, which leaves part of the vessel wall unaffected (arrow). Collagen is stained blue 22

23 ATHEROSCLEROSIS Clinical Consequences: Large elastic arteries (e.g., aorta, carotid, and iliac arteries) and large and medium-sized muscular arteries (e.g., coronary, renal, and popliteal arteries) are the vessels most commonly involved by atherosclerosis. The major clinical consequences of atherosclerosis are: Myocardial infarction Cerebral infarction (stroke) Aortic aneurysms Renal artery narrowing Peripheral vascular disease (Intermittent claudication, gangrene of extremities) Intermittent claudication: An aching, crampy, tired and sometimes burning pain in the legs that comes and goes. It typically occurs with walking and disappears with rest, due to poor blood circulation in the arteries of the legs. 23

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25 ATHEROSCLEROSIS Clinical Consequences: Unstable plaques can cause dramatic and potentially fatal ischemic complications related to acute plaque rupture, thrombosis, or embolization Stable plaques can produce symptoms related to chronic ischemia by narrowing vessels Vulnerable and stable atherosclerotic plaque. Stable plaques have densely collagenized and thickened fibrous caps with minimal inflammation and negligible underlying atheromatous cores, whereas vulnerable plaques have thin fibrous caps, large lipid cores, and increased inflammation. (Adapted from Libby P: Circulation 91:2844, 1995.) 25

26 ATHEROSCLEROSIS Clinical Consequences: Plaque erosion or rupture typically triggers thrombosis, leading to partial or complete vascular obstruction and often tissue infarction. 26

27 ATHEROSCLEROSIS Clinical Consequences: Atherosclerotic stenosis: Critical stenosis occurs when chronic occlusion limits blood flow so severely that tissue demand exceeds supply (70% fixed occlusion). Ex: Bowel ischemia, sudden cardiac death, ischemic heart disease, ischemic encephalopathy, and intermittent claudication (ischemic leg pain). Acute Plaque Changes: Rupture/fissuring, exposing highly thrombogenic plaque constituents. Erosion/ulceration, exposing the thrombogenic subendothelial basement membrane to blood. Hemorrhage into the atheroma, expanding its volume. 27

28 Plaque Changes: ATHEROSCLEROSIS Rupture, ulceration, or erosion of the luminal surface of atheromatous plaques exposes highly thrombogenic substances and induces thrombus formation. Thrombi may partially or completely occlude the lumen, leading to tissue ischemia (e.g., in the heart). If the patient survives, thrombi become organized and incorporated into the growing plaque. Hemorrhage into a plaque: Rupture of the overlying fibrous cap or of the thin-walled vessels in the areas of neovascularization can cause intra-plaque hemorrhage; the resulting hematoma may cause rapid plaque expansion or plaque rupture. Atheroembolism: Ruptured plaque can discharge debris into the blood, producing microemboli composed of plaque contents. Aneurysm formation: Atherosclerosis-induced pressure or ischemic atrophy of the underlying media, with loss of elastic tissue, causes structural weakening that can lead to aneurysmal dilation and rupture. 28

29 References ROBBINS Basic Pathology 9 th Edition Source of the cover: 29

30 Thank you 30