- Slides: 111
Cardiovascular System Dr. Sufia Husain
Ischemic Heart Disease (Coronary Heart Disease) • A group of closely related syndromes caused by an imbalance between the myocardial oxygen demand blood supply. – Angina pectoris (chest pain). – Acute myocardial infarction. – Sudden cardiac death. – Chronic ischemic heart disease with congestive heart failure.
Ischemic Heart Disease: Epidemiology(coronary atherosclerosis) Peak incidence: 60 y for males and 70 y for females. Men are more affected than women until the ninth decade. Contributing factors: ◦ Hypertension. ◦ Diabetes mellitus. ◦ Smoking. ◦ High levels of LDL. ◦ Genetic factors (direct or indirect). ◦ Lack of exercise.
Pathogenesis of Ischemic Heart Disease • 1) Role of Critical stenosis or obstruction: (>=75% of the lumen of one or more coronary arteries by atherosclerotic plaque).
Pathogenesis of Ischemic Heart Disease 2) Role of Acute Plaque Change: • In most patients the myocardial ischemia underlying unstable angina, acute MI, and (in many cases) sudden cardiac death is precipitated by abrupt plaque change followed by thrombosis.
Pathogenesis of Ischemic Heart Disease • Most often, the initiating event is disruption of previously only partially stenosing plaques with any of the following: • Rupture/fissuring, exposing the highly thrombogenic plaque constituents • Erosion/ulceration, exposing the thrombogenic subendothelial basement membrane to blood • Hemorrhage into the atheroma, expanding its volume.
Pathogenesis of Ischemic Heart Disease 3) Role of Coronary Thrombus: In acute transmural MI thrombus superimposed on a disrupted but previously only partially stenotic plaque converts it to a total occlusion. In unstable angina, acute subendocardial infarction, or sudden cardiac death, the extent of luminal obstruction by thrombosis is usually incomplete. Thrombus in coronary artery can also embolize.
Pathogenesis of Ischemic Heart Disease 4) Role of Vasoconstriction: • Vasoconstriction compromises lumen size, and, by increasing the local mechanical forces, can potentiate plaque disruption.
Pathogenesis of Ischemic Heart Disease 5) Role of Inflammation: Inflammatory processes play important roles at all stages of atherosclerosis. Entry of leukocytes into the wall is a consequence of the release of chemokines by endothelial cells, and the increased expression of adhesion proteins in these cells. At later stages of atherosclerosis, destabilization and rupture of the plaque may involve the secretion of metalloproteinases by macrophages. These enzymes weaken the plaque by digesting collagen at the fibrous cap.
A. Plaque rupture without superimposed thrombus in a patient who died suddenly. B. Acute coronary thrombosis superimposed on an atherosclerotic plaque with focal disruption of the fibrous cap, triggering fatal myocardial infarction. C. Massive plaque rupture with superimposed thrombus, also triggering a fatal myocardial infarction (special stain highlighting fibrin in red). In both
Ischemic Heart Disease: Pathogenesis
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ENDOTHELIAL CELLS • ECs comprise the single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium. Endothelial structural and functional integrity is fundamental to the maintenance of vessel wall homeostasis and normal circulatory function.
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Smooth muscle cells • SMCs are predominant cellular element of the vascular media • SMCs are responsible for vasoconstriction and dilation in response to normal or pharmacologic stimuli. • They also synthesize collagen, elastin, and proteoglycans; and elaborate growth factors and cytokines. They migrate to the intima and proliferate following vascular injury. • Thus, SMCs are important elements of both normal vascular repair and pathologic processes such as atherosclerosis.
Smooth muscle cells • Vascular injury ( endothelial injury/dysfunction) stimulates SMC growth. Reconstitution of the damaged vascular wall is a physiologic healing response that includes the formation of a neointima, in which SMCs (1) migrate from the media to the intima, (2) multiply as intimal SMCs, and (3) synthesize and deposit ECM
Smooth muscle cells • During the healing response, SMCs undergo changes that resemble dedifferentiation. In the intima they lose the capacity to contract and gain the capacity to divide. • Intimal SMCs may return to a nonproliferative state when either the overlying endothelial layer is reestablished following acute injury or the chronic stimulation ceases.
Arteriosclerosis (literally, "hardening of the arteries") is a generic term for thickening and loss of elasticity of arterial walls. Three patterns of arteriosclerosis are recognized; they vary in pathophysiology and clinical and pathological consequences. 1)Atherosclerosis, the most frequent and important pattern
Arteriosclerosis 2)Mönckeberg medial calcific sclerosis is characterized by calcific deposits in muscular arteries in persons older than age 50. They do not encroach on the vessel lumen. 3)Arteriolosclerosis affects small arteries and arterioles. There are two anatomic variants, hyaline and hyperplastic, both associated with thickening of vessel walls with luminal narrowing that may cause ischemic injury. Most often associated with hypertension and diabetes mellitus.
Atherosclerosis • Atherosclerosis is characterized by intimal lesions called atheromas, or atheromatous or fibrofatty plaques, which protrude into and obstruct vascular lumens and weaken the underlying media. They may lead to serious complications
Atherosclerosis: Morphology Fatty streaks are the earliest lesion of atherosclerosis. They are composed of lipid-filled foam cells. They are not significantly raised and thus do not cause any disturbance in blood flow. Fatty streaks begin as multiple yellow, flat spots less than 1 mm in diameter that coalesce into elongated streaks, 1 cm long or longer. They contain T lymphocytes and extracellular lipid in smaller amounts than in plaques.
Fatty streak—a collection of foam cells in the intima. A. Aorta with fatty streaks ( arrows), associated largely with the ostia of branch vessels. B. Close-up photograph of fatty streaks from the aorta of an experimental hypercholesterolemic rabbit shown after staining with Sudan red, a lipid-soluble dye, again illustrating the relationship of the lesions to the two-branch vessel ostia. C. Photomicrograph of fatty streak in an experimental hypercholesterolemic rabbit, demonstrating intimal macrophage-derived foam cells ( arrow). Slide 12. 9
Morphology • The key processes in atherosclerosis are intimal thickening and lipid accumulation. An atheroma or atheromatous plaque consists of a raised focal lesion initiating within the intima, having a soft, yellow, grumous core of lipid (mainly cholesterol and cholesterol esters), covered by a firm, white fibrous cap.
Morphology • The atheromatous plaques appear white to whitish yellow and impinge on the lumen of the artery. They vary in size from approximately 0. 3 to 1. 5 cm in diameter but sometimes coalesce to form larger masses. Atherosclerotic lesions usually involve only a partial circumference of the arterial wall ("eccentric" lesions) and are patchy and variable along the vessel length.
Atherosclerosis: Morphology • The most heavily involved vessels are the abdominal aorta then coronary arteries, the popliteal arteries, the internal carotid arteries, and the vessels of the circle of Willis.
Atherosclerosis: Morphology Atherosclerotic plaques have three principal components: • (1) cells, including SMCs, macrophages, and other leukocytes • (2) ECM, including collagen, elastic fibers, and proteoglycans • (3) intracellular and extracellular lipid. These components occur in varying proportions.
Atherosclerosis: Morphology • Typically, the superficial fibrous cap is composed of SMCs and relatively dense ECM. Beneath and to the side of the cap (the "shoulder") is a cellular area consisting of macrophages, SMCs, and T lymphocytes. • Deep to the fibrous cap is a necrotic core, containing a disorganized mass of lipid (primarily cholesterol and cholesterol esters), cholesterol clefts, debris from dead cells, foam cells, fibrin, variably organized thrombus, and other plasma proteins.
Atherosclerosis: Morphology • Foam cells are large, lipid-laden cells that derive predominantly from blood monocytes (tissue macrophages), but SMCs can also imbibe lipid to become foam cells. • Around the periphery of the lesions, there is usually evidence of neovascularization (proliferating small blood vessels). Typical atheromas contain relatively abundant lipid. • Atheromas often undergo calcification.
Major components of well-developed atheromatous plaque: fibrous cap composed of proliferating smooth muscle cells, macrophages, lymphocytes, foam cells, and extracellular matrix. The necrotic core consists of cellular debris, extracellular lipid with cholesterol crystals, and foamy macrophages. Slide 12. 6
Gross views of atherosclerosis in the aorta. A. Mild atherosclerosis composed of fibrous plaques, one of which is denoted by the arrow. B. Severe disease with diffuse and complicated lesions. Slide 12. 7
Histologic features of atheromatous plaque in the coronary artery. A. Overall architecture demonstrating a fibrous cap (F) and a central lipid core (C) with typical cholesterol clefts. The lumen (L) has been moderately narrowed. Note the plaque-free segment of the wall ( arrow). In this section, collagen has been stained blue (Masson trichrome stain). B. Higher-power photograph of a section of the plaque shown in A, stained for elastin ( black) demonstrating that the internal and external elastic membranes are destroyed and the media of the artery is thinned under the most advanced plaque ( arrow). C. Higher-magnification photomicrograph at the junction of the fibrous cap and core showing scattered inflammatory cells, calcification ( broad arrow), and neovascularization ( small arrows). Slide 12. 8
American Heart Association classification of human atherosclerotic lesions from the fatty dot (type I) to the complicated type VI lesion. The diagram also includes growth mechanisms and clinical correlations. Slide 12. 11
COMPLICATIONS The advanced lesion of atherosclerosis is at risk for the following pathological changes that have clinical significance: 1) Focal rupture, ulceration, or erosion of the luminal surface of atheromatous plaques may result in exposure of highly thrombogenic substances that induce thrombus formation or discharge of debris into the bloodstream, producing microemboli composed of lesion contents (cholesterol emboli or atheroemboli).
COMPLICATIONS 2) Hemorrhage into a plaque, especially in the coronary arteries, may be initiated by rupture of either the overlying fibrous cap or the thin-walled capillaries that vascularize the plaque. A contained hematoma may expand the plaque or induce plaque rupture.
COMPLICATIONS 3)Superimposed thrombosis, the most feared complication, usually occurs on disrupted lesions (those with rupture, ulceration, erosion, or hemorrhage) and may partially or completely occlude the lumen. Thrombi may heal and become incorporated into and thereby enlarge the intimal plaque.
4)Aneurysmal dilation may result from ATHinduced atrophy of the underlying media, with loss of elastic tissue, causing weakness and potential rupture 5) Calcifications.
Natural history of atherosclerosis Slide 12. 5
Risk Factors for Atherosclerosis Major Nonmodifiable • Increasing age • Male gender • Family history • Genetic abnormalities Potentially. Controllable • Hyperlipidemia • Hypertension • Cigarette smoking • Diabetes
Risk Factors for Atherosclerosis Lesser, Uncertain, or Nonquantitated • Obesity • Physical inactivity • Stress ("type A" personality) • Postmenopausal estrogen deficiency • High carbohydrate intake • Alcohol • Lipoprotein Lp(a) • Hardened (trans)unsaturated fat intake • Chlamydia pneumoniae
PATHOGENESIS: response to injury hypothesis • This concept, called the response to injury hypothesis, considers atherosclerosis to be a chronic inflammatory response of the arterial wall initiated by injury to the endothelium. Moreover, lesion progression is sustained by interaction between modified lipoproteins, monocyte-derived macrophages, T lymphocytes, and the normal cellular constituents of the arterial wall.
Processes in the response to injury hypothesis. 1, Normal. Slide 12. 13
2, Endothelial injury with adhesion of monocytes and platelets (the latter to denuded endothelium). Slide 12. 14
3, Migration of monocytes (from the lumen) and smooth muscle cells (from the media) into the intima. Slide 12. 15
4, Smooth muscle cell proliferation in the intima. Slide 12. 16
5, Well-developed plaque. Slide 12. 17
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PATHOGENESIS: response to injury hypothesis Central to this thesis are the following: • Accumulation of lipoproteins, mainly LDL, with its high cholesterol content, in the vessel wall • Chronic endothelial injury, usually subtle, yielding increased permeability, leukocyte adhesion, and thrombotic potential.
PATHOGENESIS: response to injury hypothesis • Adhesion of blood monocytes (and other leukocytes) to the endothelium, followed by their migration into the intima and their transformation into macrophages and foam cells • Adhesion of platelets • Release of factors from activated platelets, macrophages, or vascular cells that cause migration of SMCs from media into the intima
PATHOGENESIS: response to injury hypothesis • Proliferation of smooth muscle cells in the intima, and elaboration of extracellular matrix, leading to the accumulation of collagen and proteoglycans • Enhanced accumulation of lipids both within cells (macrophages and SMCs) and extracellularly.
PREVENTION • primary prevention programs, aimed at either delaying atheroma formation or causing regression of established lesions in persons who have never suffered a serious complication of atherosclerotic coronary artery disease • secondary prevention programs, intended to prevent recurrence of events such as myocardial infarction in patients with symptomatic disease.
PREVENTION • based on risk factor modification: abstention from or cessation of cigarette smoking, control of hypertension, weight reduction and increased exercise, moderation of alcohol consumption, and, most importantly, lowering total and LDL blood cholesterol levels while increasing HDL. on
Angina pectoris • Angina pectoris is a symptom complex of IHD characterized by paroxysmal and usually recurrent attacks of substernal or precordial chest discomfort (variously described as constricting, squeezing, choking, or knifelike) caused by transient (15 seconds to 15 minutes) myocardial ischemia that falls short of inducing the cellular necrosis that defines infarction.
Angina pectoris • There are three overlapping patterns of angina pectoris: (1) stable or typical angina, (2) Prinzmetal or variant angina, and (3) unstable or crescendo angina
Angina pectoris Stable angina, the most common form and therefore called typical angina pectoris, appears to be caused by the reduction of coronary perfusion to a critical level by chronic stenosing coronary atherosclerosis; this renders the heart vulnerable to further ischemia whenever there is increased demand, such as that produced by physical activity, emotional excitement, or any other cause of increased cardiac workload. Episodic chest pain associated with exertion or some other form of stress.
Angina pectoris • The pain is described as a crushing or squeezing substernal sensation, which may radiate down the left arm. Typical angina pectoris is usually relieved by rest (thereby decreasing demand) or nitroglycerin, a strong vasodilator.
Angina Pectoris • Prinzmetal variant angina is an uncommon pattern of episodic angina that occurs at rest and is due to coronary artery spasm. Prinzmetal angina generally responds promptly to vasodilators, such as nitroglycerin and calcium channel blockers.
Angina Pectoris Unstable or crescendo angina refers to a pattern of pain that occurs with progressively increasing frequency, is precipitated with progressively less effort, often occurs at rest, and tends to be of more prolonged duration. It is induced by disruption of an atherosclerotic plaque with superimposed partia) thrombosis and possibly embolization or vasospasm (or both). Unstable angina is often the precursor of subsequent acute MI. Thus this referred to as preinfarction angina.
Myocardial Infarction • Definition: MI, also known as "heart attack, " is the death of cardiac muscle resulting from ischemia. • Risks are the same as those of coronary atherosclerosis.
Pathogenesis of MI • Any form of coronary artery disease. • In the typical case of MI, the following sequence of events can be proposed: • The initial event is a sudden change in the morphology of an atheromatous plaque, that is, disruption-manifest as intraplaque hemorrhage, erosion or ulceration, or rupture or fissuring.
Pathogenesis of MI • Exposed to subendothelial collagen and necrotic plaque contents, platelets undergo adhesion, aggregation, activation, and release of potent aggregators including thromboxane A 2, serotonin, and platelet factors 3 and 4. • Vasospasm is stimulated by platelet aggregation and the release of mediators.
Pathogenesis of MI • Other mediators activate the extrinsic pathway of coagulation, adding to the bulk of the thrombus. • Frequently within minutes, the thrombus evolves to completely occlude the lumen of the coronary vessel
Pathogenesis of MI • Most common cause is thrombosis on a preexisting disrupted atherosclerotic plaque. • Platelet aggregate and vasospasm may participate but are rarely the sole cause of occlusion. • Hypoperfusion + atherosclerosis may lead to subendocerdial infarct without thrombosis.
Pathogenesis of MI • Myocardial necrosis begins within 20 -30 minutes, mostly starting at the subendocardial region (less perfused, high intramural pressure). • Infarct reaches its full size within 3 -6 hrs. , during this period, lysis of the thrombus by streptokinase or tpa, may limit the size of the infarct.
Pathogenesis of MI • Table 12 -4. Approximate Time of Onset of Key Events in Ischemic Cardiac Myocytes • Feature. Time. Onset of ATP depletion. Seconds. Loss of contractility<2 min. ATP reducedto 50% of normal 10 minto 10% of normal 40 min. Irreversible cell injury 2040 min. Microvascular injury>1 hr
Pathogenesis of MI Location of the MI is determined by the site of the occlusion and by the anatomy of coronary circulation. Left anterior descending(40 -50%): anterior and apical left ventricle and anterior two thirds of interventricular septum. Right coronary artery(30 -40%): posterior wall of the left ventricle, posterior one third of interventricular septum (rt. Dominant coronary circulation). Left circumflex: lateral wall of lt. Ventricle (posterior wall in persons with left-dominant coronary circulation).
Pathogenesis of MI • The precise location, size, and specific morphologic features of an acute myocardial infarct depend on: • The location, severity, and rate of development of coronary atherosclerotic obstructions • The size of the vascular bed perfused by the obstructed vessels • The duration of the occlusion
Pathogenesis of MI • The metabolic/oxygen needs of the myocardium at risk • The extent of collateral blood vessels • The presence, site, and severity of coronary arterial spasm • Other factors, such as alterations in blood pressure, heart rate, and cardiac rhythm.
Pathogenesis of MI Myocardial necrosis begins within 20 -30 minutes, mostly starting at the subendocardial region (less perfused, high intramural pressure). Infarct reaches its full size within 3 -6 hrs. , during this period, lysis of the thrombus by streptokinase or tpa, may limit the size of the infarct.
Myocardial Infarction: Morphology • Coagulation necrosis and inflammation. • Formation of granulation tissue. • Organization of the necrotic tissue to form a fibrous scar. • Morphology is dependent on age of the infarct, its size, recurrence, reperfusion.
Myocardial Infarction: Morphology Time Gross Microscopy 0 -30 min No change 1 -2 hr No change Few wavy fibers at margin of infarct 4 -12 hr No change Early coagulation necrosis, edema, occasional neutrophils, minimal hemorrhage 18 -24 hr Slight pallor Continuing coagulation necrosis(nuclear pyknosis, and disintegration, cytoplasmic eosinphilia), contraction band, necrosis at periphery of infarct, neutrophilic infiltrate 24 -72 hr Pallor Complete coagulation necrosisof myofibers, heavy neutrophilic infiltrate with early fragmentation of neutrophil nuclei 4 -7 days Central pallor with hyperemic border Macrophages appear, early disintegration and phagocytosis of necrotic fibers, granulation tissue visible at edge of infarct 10 days Maximally yellow, shrunken; purple border Well-developed phagocytosis, prominent granulation tissue in peripheral areas of infarct 7 -8 wks Firm gray Fibrosis
13. 16 Figure 13– 8 (p. 560) Microscopic features of myocardial infarction. A. One-day-old infarct showing coagulative necrosis, wavy fibers with elongation, and narrowing, compared with adjacent normal fibers (lower right). Widened spaces between the dead fibers contain edema fluid and scattered neutrophils. B. Dense polymorphonuclear leukocytic infiltrate in an area of acute myocardial infarction of 3 to 4 days' duration. C. Nearly complete removal of necrotic myocytes by phagocytosis (approximately 7 to 10 days).
D. Granulation tissue with a rich vascular network and early collagen deposition, approximately 3 weeks after infarction. E. Well-healed myocardial infarct with replacement of the necrotic fibers by dense collagenous scar. A few residual cardiac muscle cells are present. (In D and E, collagen is highlighted as blue in this Masson trichrome stain. )
Complications of MI • Myocardial rupture • Arrhythmias. Many patients have conduction disturbances and myocardial irritability following MI, which undoubtedly are responsible for many of the sudden deaths • Pericarditis
Complications of MI • Infarct extension. New necrosis may occur adjacent to an existing infarct. • Infarct expansion • Mural thrombus. With any infarct, the combination of a local myocardial abnormality in contractility (causing stasis) with endocardial damage (causing a thrombogenic surface) can foster mural thrombosis and, potentially, thromboembolism
Complications of MI • Ventricular aneurysm. In contrast to false aneurysms mentioned above, true aneurysms of the ventricular wall are bounded by myocardium that has become scarred. • Papillary muscle dysfunction.
Complications of MI • • • External rupture of the infarct. Mural thrombi. Acute pericarditis. Ventricular aneurysms. Progressive late heart failure is discussed as chronic IHD below.
Myocardial Infarction: Clinical Features Pain: ◦ Severe crushing substernal chest pain, which may radiate to the neck, jaw, epigastrum, shoulder or left arm. ◦ Pain lasts for hours to days and is not relieved by nitroglycerin. ◦ Absent in 20 -30% of patients (diabetics, hypertensive, elderly). Pulse is rapid and weak. Diaphoresis. Dyspnea. Cardiogenic shock in massive MI(>40%of lt. ventricle).
Myocardial Infarction: Electrocardiographic Abnormalities • • Changes of Q waves. ST-segment abnormalities. T-wave inversion. Arrhythmias.
Myocardial Infarction: Outcomes Sudden coronary death due to ventricular arrhythmia (25%). No complications in 10 -20%. 80 -90% experience one or more of the followings: ◦ Cardiac arrhythmia (75 -90%). ◦ Left ventricular failure with mild to severe pulmonary edema (60%). ◦ Cardiogenic shock (10%). ◦ Rupture of free wall, septum, papillary muscle (4 -8%). ◦ Thromboembolism (15 -49%).
Myocardial Infarction: Laboratory Evaluation • Creatine kinase (CK) … CK-MB. – Rise 2 -4 hrs, peaks 18 hrs, persists 48 hrs. • Lactate dehydrogenase (LD)… LD 1. – Rise 24 hrs, peaks 72 hrs, persists 72 hrs. • Troponins: c. Tn. T, c. Tn. I (more specific). – Persists for 4 -7 days.
Sudden Cardiac Death • Morphology: – Marked degree of coronary atherosclerosis. – ? acute rupture of plaque, thrombosis, vasospasm, fatal ventricular arrhythmia. – Acute or remote myocardial infarction.
Sudden Cardiac Death • This catastrophe strikes down about 300, 000 to 400, 000 individuals annually in the United States. Sudden cardiac death (SCD) is most commonly defined as unexpected death from cardiac causes early after symptom onset (usually within 1 hour) or without the onset of symptoms.
Sudden Cardiac Death • Atherosclerosis is the most commom cause. The non-atherosclerotic causes include the following: • Congenital structural or coronary arterial abnormalities • Aortic valve stenosis • Mitral valve prolapse • Myocarditis • Dilated or hypertrophic cardiomyopathy • Pulmonary hypertension
Sudden Cardiac Death • Hereditary or acquired abnormalities of the cardiac conduction system • Isolated hypertrophy, hypertensive or unknown cause. Increased cardiac mass is an independent risk factor for cardiac death; thus, some young patients who die suddenly, including athletes, have hypertensive hypertrophy or unexplained increased cardiac mass as the only finding
Sudden Cardiac Death • The ultimate mechanism of SCD is most often a lethal arrhythmia (e. g. , asystole, ventricular fibrillation
Hypertension and Hypertensive Vascular Disease • Hypertension: Definition: a sustained diastolic pressure more than 90 mm hg or a sustained systolic pressure in excess of 140 mm hg. • Hypertension is an important risk factor in: – Coronary heart disease. – Cerebrovascular accidents. – May lead to: • Congestive heart failure. • Aortic dissection. • Renal failure.
Hypertension: Types/ Cause • Primary or essential hypertension(90 -95%). • Secondary hypertension(5 -10%): – Renal: • • • Acute glomerulonephritis. Chronic renal disease. Renal artery stenosis. Renal vasculitis. Renin-producing tumors.
Hypertension: Types/ Cause • Secondary hypertension: – Endocrine: • • • Adrenocortical hyperfunction (Cushing’s syndrome) Oral contraceptives. Pheochromocytoma. Acromegaly. Myxedema. Thyrotoxicosis (systolic).
Hypertension: Types/ Cause • Secondary hypertension: – Vascular: • Coarctation of aorta. • Polyarteritis nodosa. • Aortic insufficiency (systolic) – Neurogenic: • Psychogenic. • Increased intracranial pressure. • Polyneuritis, bulbar poliomyelitis, others.
Hypertension: Types/ Clinical • Benign: – Modest level. – Fairly stable over years to decades. – Compatible with long life. • Malignant(5%): – Rapidly rising blood pressure. – Severe hypertension (diastolic>120) – Renal failure. – Retinal hemorrhages and exudates (w/wo papilledema). – Leads to death in 1 or 2 years if untreated.
Hypertension: Pathogenesis • Blood pressure: BP = Cardiac Output x Peripheral Resistance
Atriopeptin: peptides secreted by heart atria in response to volume expansion: inhibit Na reabsorption in distal tubules and cause vasodilation Glomerular filtration rate
Hypertension: Possible Factors • Genetic: – Twin studies. – Familial clustering. – Gene linkage studies (red in previous slide) • Environmental: – Low incidence in native Chinese as compared to immigrants to US. – May include: stress, obesity, inactivity, and heavy consumption of salt.
1. Behavioural or neurogenic factors 2. release of vasoconstrictors (endothelin. , angiotensin II) 3. 1 ry sensitivity of vascular smooth muscle Hypertrophy, remodeling and hyperplasia of SMCs.
Vascular pathology in hypertension. A. Hyaline arteriolosclerosis. The arteriolar wall is hyalinized and the lumen is markedly narrowed. B. Hyperplastic arteriolosclerosis (onionskinning) causing luminal obliteration ( arrow), with secondary ischemic changes, manifested by wrinkling of the glomerular capillary vessels at the upper left )periodic acid–Schiff [PAS] stain).
Vascular pathology in hypertension. • Hyaline arteriolosclerosis: – Can also be seen in elderly without hypertension and in diabetic patients. – Leads to benign nephrosclerosis due to diffuse renal ischemia. • Hyperplastic arteriolosclerosis: – Characteristic of malignant hypertension. – May be associated with necrotizing arteriolitis.
Heart in Hypertension • Clinically: • Early: no symptoms (chest x-ray, echo-, electrocardiography). • Late: heart failure, symptoms and signs of ischemic heart disease. • Hypertensive heart disease (HHD) is the response of the heart to the increased demands induced by systemic hypertension. 74 Pulmonary hypertension also causes heart disease and is referred to as rightsided HHD, or cor pulmonale
SYSTEMIC (LEFT-SIDED) HYPERTENSIVE HEART DISEASE • In hypertension, hypertrophy of the heart is an adaptive response to pressure overload that can lead to myocardial dysfunction, cardiac dilation, CHF, and sudden death. • The minimal criteria for the diagnosis of systemic HHD are the following: (1) left ventricular hypertrophy (usually concentric) in the absence of other cardiovascular pathology that might have induced it and (2) a history or pathologic evidence of hypertension
SYSTEMIC (LEFT-SIDED) HYPERTENSIVE HEART DISEASE • Morphology. Hypertension induces left ventricular pressure overload hypertrophy without dilation of the left ventricle. The thickening of the left ventricular wall and increase in the weight of the heart and increase in the overall cardiac size. In time, the increased thickness of the left ventricular wall imparts a stiffness that impairs diastolic filling. This often induces left atrial enlargement
SYSTEMIC (LEFT-SIDED) HYPERTENSIVE HEART DISEASE • Microscopically, the earliest change of systemic HHD is an increase in the transverse diameter of myocytes, which may be difficult to appreciate on routine microscopy. At a more advanced stage, the cellular and nuclear enlargement becomes somewhat more irregular, with variation in cell size among adjacent cells, and interstitial fibrosis.
SYSTEMIC (LEFT-SIDED) HYPERTENSIVE HEART DISEASE Depending on the severity, duration, and underlying basis of the hypertension, and on the adequacy of therapeutic control, the patient may • (1) enjoy normal longevity and die of unrelated causes, (2) develop progressive IHD owing to the effects of hypertension in potentiating coronary atherosclerosis, • (3) suffer progressive renal damage or cerebrovascular stroke, • (4) experience progressive heart failure.
SYSTEMIC (LEFT-SIDED) HYPERTENSIVE HEART DISEASE • The risk of sudden cardiac death is also increased. Effective control of hypertension can prevent or lead to regression of cardiac hypertrophy and its associated risks.
PULMONARY (RIGHT-SIDED) HYPERTENSIVE HEART DISEASE (COR PULMONALE) • Cor pulmonale, as pulmonary HHD is frequently called, consists of right ventricular hypertrophy, dilation, and potentially failure secondary to pulmonary hypertension caused by disorders of the lungs or pulmonary vasculature. Pulmonary HHD is the right-sided counterpart of left-sided (systemic) HHD.
PULMONARY (RIGHT-SIDED) HYPERTENSIVE HEART DISEASE (COR PULMONALE) • Although right ventricular dilation and thickening caused either by diseases of the left side of the heart or congenital heart diseases are generally excluded by this definition of cor pulmonale, pulmonary venous hypertension that follows left-sided heart diseases of various etiologies is quite common
PULMONARY (RIGHT-SIDED) HYPERTENSIVE HEART DISEASE (COR PULMONALE) Cor pulmonale may be acute or chronic, depending on the suddenness of development of the pulmonary hypertension. Acute cor pulmonale can follow massive pulmonary embolism. Chronic cor pulmonale usually implies right ventricular hypertrophy (and dilation) secondary to prolonged pressure overload caused by obstruction of the pulmonary arteries or arterioles or compression or obliteration of septal capillaries (e. g. , owing to primary pulmonary hypertension or emphysema
PULMONARY (RIGHT-SIDED) HYPERTENSIVE HEART DISEASE (COR PULMONALE) • Morphology. In acute cor pulmonale, there is marked dilation of the right ventricle without hypertrophy. In chronic cor pulmonale, the right ventricular wall thickens, sometimes up to 1. 0 cm or more, and may even come to approximate that of the left ventricle.