Lesson 17

"Hypertension. Ischemic Heart Disease."

Key points:
1.Cerebrovascular disease: definition, risk factors, classification, background diseases. Infarction (ischemic stroke) of the brain. Morphological classification and characterization,consequences. Selective neuron necrosis (ischemic encephalopathy): morphologicalcharacteristics. Hemorrhagic stroke, cerebral hemorrhage, subarachnoid hemorrhage:morphological characteristics, complications, consequences.
2. Essential hypertension (hypertension) and secondary (symptomatic) hypertension.
3. Benignand malignant hypertension.
4. Hypertension: risk factors, morphological changes in bloodvessels, heart, kidneys and other organs.
5.Coronary heart disease. Angina pectoris: classification, clinical and morphological characteristics.
6. Myocardial infarction: causes, classification, dynamics of morpho-functionalchanges in the myocardium. Consequences, complications, causes of death.
7. Chroniccoronary heart disease: clinical and morphological characteristics, complications, causes of death.

Sources:
1. Kumar, Vinay, Abul K. Abbas, and Jon C. Aster. Robbins and Cotran Pathologic Basis of Disease. Ninth edition. Philadelphia, PA: Elsevier/Saunders, 2015. P.7-64
2. Kumar, Vinay, Abul K Abbas, Jon C Aster, and Stanley L. 1915-2003 Robbins. RobbinsBasic Pathology. 10th ed. Philadelphia, PA: Elsevier/Saunders, 2018. P.1-33, 51
3. Klatt, Edward C. Robbins and Cotran Atlas of Pathology. Third edition. Philadelphia, PA:Elsevier Saunders, 2015.
4. Klatt, Edward C., and Vinay Kumar. Robbins and CotranReview of Pathology. Fourth edition. Philadelphia, PA: Elsevier Saunders, 2015. P.3-17
5. Harsh Mohan. Essential Pathology for Dental Students.Fourth edition. Jaypee Brothers,Medical Publishers Pvt. Limited, 2011. P.1-77

Cardiac hypertrophy, gross

Note prominent concentric left ventricular hypertrophy. The number of myocardial fiers does not increase, but their size can increase in response to an increased workload, leading to marked thickening of the LV. Increased pressure load from systemic hypertension is the most common cause of left ventricular hypertrophy. An increased volume load from aortic regurgitation can also lead to hypertrophy. Some degree of cardiac chamber dilation also accompanies ventricular failure. A relatively decreased capillary density, increased firous tissue, and synthesis of abnormal proteins predispose to heart failure.

Coronary atherosclerosis, gross

A minimal amount of coronary atherosclerosis, with a few scattered yellow lipid plaques , is shown on the intima of the opened coronary artery traversing the epicardial surface of a heart. The degree of atherosclerosis here is not great enough to cause signifiant luminal narrowing but could be the harbinger of worse atherosclerosis to come, if plaques continue to enlarge. Atherosclerosis is initiated with endothelial damage and inflmmation with leukocyte elaboration of cytokines, such as tumor necrosis factor (TNF), interleukin-1 (IL-1), and interferon-γ (IFN-γ). This process is promoted by uptake of increased circulating oxidized LDL cholesterol into macrophages.

Coronary atherosclerosis, gross

These cross-sections of the left anterior descending coronary artery show atherosclerosis with more pronounced luminal narrowing at the left, the more proximal portion of this artery. Atherosclerosis is generally worse at the origin of a coronary artery and in the fist few centimeters, where turbulent blood flw is greater. This turbulent flw over many years promotes endothelial injury that favors inflmmation with insudation of lipids to promote formation of atheromas. With lifestyle modifiations, this process is reversible.

Coronary thrombosis, gross

One of the severe complications of coronary atherosclerosis, shown here with thickened arterial walls with yellow-tan plaques that narrow the arterial lumen, is thrombosis. The dark red thrombus occludes this anterior descending coronary artery, opened longitudinally. The thrombotic occlusion leads to ischemia or infarction of the myocardium supplied by the artery. One possible outcome of coronary thrombosis is sudden death. Other complications include ongoing arrhythmias and congestive heart failure.

Coronary thrombosis, microscopic

The recent thrombus shown here nearly occludes the remaining small lumen of this coronary artery already narrowed from severe atherosclerosis. Note the firointimal proliferation with cholesterol clefts. Endothelial damage with platelet activation promotes thrombosis. A small dose of aspirin taken each day helps reduce platelet function, making the platelets less sticky and less prone to participate in thrombotic events.

Myocardial infarction, gross

The interventricular septum is sectioned to reveal an extensive acute MI. The dead muscle is tanyellow, with a surrounding hyperemic border. This appearance is characteristic of an infarction that is 3 to 7 days old. Serum creatinine kinase (CK), specifially the CK-MB isozyme more specifi to heart, and troponin I are released from damaged myofiers and start to increase 3 to 4 hours after the initial ischemic event. CK-MB peaks about 1 day later, then declines to negligible levels by 3 days. The troponin I level remains increased for 10 to 14 days. Serum myoglobin can be increased starting 3 hours after MI, but it is not specifi for myocardium.

Myocardial infarction, gross

This axial section reveals a large MI involving the anterior left ventricular wall and interventricular septum in the distribution of the left anterior descending coronary artery. Note the yellowish area of necrosis with the hyperemic border that is nearly transmural. Radionuclide imaging would show decreased uptake into this region. Echocardiography would show diminished ventricular wall motion with such a large infarction, and the EF would be decreased. Electrocardiographic changes could include ST segment elevation followed by T wave inversion and by development of Q waves.

Myocardial infarction, gross

In cross-section, the point of rupture of the left ventricular free wall myocardium is shown. In this case, an MI 3 weeks prior accounts for the ventricular wall thinning shown here; a subsequent MI occurred and ruptured through an already thinned ventricular wall 3 days later. The mitral valve with chordae tendineae and the papillary muscles appear normal here. Rupture is most likely to occur 3 to 7 days after a transmural infarction, when the necrotic muscle is soft and before any signifiant amount of organization with ingrowth of capillaries and firoblasts has occurred.

Myocardial infarction, microscopic

The earliest histologic change seen with acute MI during the fist 24 hours is contraction band necrosis. These myocardial fiers are beginning to lose cross-striations, and the nuclei are not clearly visible in most of the myocytes shown here. Note the many irregular, darker pink, wavy contraction bands extending across the fiers. Serologic markers for infarction include nonspecifi myoglobin and the more specifi markers of cardiac muscle injury, including CK-MB and troponin I. Use of thrombolytic agents, percutaneous transluminal coronary angioplasty, and coronary arterial bypass grafting are methods to help restore blood flw and prevent further damage.

Myocardial infarction, microscopic

This trichrome stain shows the appearance of an early acute MI, less than 1 day old, with prominent reddish contraction band necrosis. Coagulative necrosis with karyolysis has led to loss of the nuclei. If the area of infarction remains small, the MI may be “silent” without signs or symptoms and detectable only with electrocardiography or serum cardiac muscle enzyme elevation. The myocardial irritability after an MI leads to electrical conduction disturbances with arrhythmias such as sinus bradycardia, heart block, asystole, and ventricular firillation.

Myocardial infarction, microscopic

This early acute MI is 1 to 2 days old. There is loss of cross-striations, and some contraction bands are seen. The cardiac fier nuclei have undergone karyolysis and are no longer visible. Some neutrophils are beginning to infitrate into this necrotic myocardium. The loss of the nuclei represents an irreversible form of cellular injury. Reperfusion of such damaged muscle may lead to increased production of toxic free radicals that can potentiate further myocardial damage. Thrombolytic therapy to treat acute coronary thrombosis is most benefiial within 30 minutes of the initial arterial occlusion.

Myocardial infarction, microscopic

This early acute MI is 2 to 3 days old. There is increasing infitration by neutrophils into the myocardium. With ongoing coagulative necrosis, the outlines of myofiers remain, but their nuclei haveundergone dissolution. At this point CK-MB is decreasing while troponins remain elevated. The extent of infarction determines residual ventricular function. A large infarct may severely reduce EF and lead to acute congestive heart failure with pulmonary congestion and edema.

Myocardial infarction, microscopic

The extensive hemorrhage in this acute MI may represent the hyperemic border, but if extensive may be the result of a reperfusion injury. The vulnerable ischemic but not yet infarcted myocardium is at greatest risk for this injury, because endothelial swelling reduces blood flw to these areas. Reperfusion injury may be mediated by oxidative stress, calcium overload, and/or acute inflmmation.

Myocardial infarction, microscopic

There is extensive acute inflmmation with neutrophils infitrating into these myofiers undergoing coagulative necrosis. This MI is 3 to 4 days old. There is an extensive acute inflmmatory cell infitrate, and the myocardial fiers are so necrotic that the outlines of them are only barely visible. Clinically, such an acute MI is marked by changes in the electrocardiogram and by an increase in troponins. In addition to chest pain, patients with MI may have a rapid, weak pulse; hypotension; diaphoresis; and dyspnea from acute left-sided congestive heart failure.

Myocardial infarction, microscopic

Toward the end of the fist week after the initial ischemic event that triggered infarction, healing of the MI becomes more prominent, with numerous capillaries, firoblasts, and macrophages filed with hemosiderin. The granulation tissue shown here becomes most prominent 2 to 3 weeks after onset of infarction. This area of granulation tissue is nonfunctional and noncontractile, reducing the EF, but it is unlikely to rupture.

Myocardial infarction, microscopic

Two to 3 weeks after the onset of MI, healing at the site of myocardial necrosis is well under way, and there is more extensive collagen deposition. This remote MI has a dense collagenous scarafter 2 months, shown here as an irregular pale area surrounded by surviving myocardial fiers. The size of the MI determines the residual EF and clinical fidings. As expected, larger MIs are more likely to become complicated by heart failure and arrhythmias.

Myocardial infarction, gross

The left ventricular free wall is on the right and the interventricular septum is at the center, with the right ventricle at the left. A remote MI has extensively involved the anterior left ventricular free wall and septum, shown here as the white appearance of the endocardial surface in the areas of extensive scarring. Involvement of the right ventricle is uncommon. This scarred area is noncontractile, and the EF and cardiac output are reduced. The papillary muscles here appear to be mostly spared.

Myocardial infarction, gross

This axial cross-section reveals a ventricular aneurysm with a very thin wall that visibly bulges out. The stasis in this aneurysm has predisposed to the mural thrombus filing it. A previous extensive transmural MI involving the free wall of the LV reduced the thickness of the myocardial wall. This infarction was so extensive that, after healing, the ventricular wall was replaced by a thin band of collagen, forming an aneurysm. The aneurysm represents noncontractile tissue that reduces stroke volume and strains the remaining myocardium.

Nephrosclerosis, gross

Intrinsic renal vascular disease with sclerosis and progressive luminal narrowing leads to patchy ischemic atrophy with focal loss of parenchyma that gives the kidney surfaces a characteristic granular appearance. The kidneys are usually slightly smaller than normal. The process may be termed benign in most older adults who continue to have normal renal function, as determined by normal serum creatinine and urea nitrogen levels. There may be a mild reduction in the glomerular fitration rate and mild proteinuria. Nephrosclerosis associated with hypertension and diabetes mellitus suggests an increased risk for renal failure.

Nephrosclerosis, microscopic

The medial thickening of the small arteries leads to progressive luminal narrowing. Nephrosclerosis slowly leads to interstitial firosis. Tubular atrophy and cast formation are common. Glomeruli are eventually affected and fist undergo collagen deposition within the Bowman space, and periglomerular firosis, with eventual total glomerular sclerosis. Nephrosclerosis may lead to mild reduction in glomerular fitration rate and loss of renal reserve capacity. Hyaline arteriolosclerosis with hypertension or diabetes mellitus is also often present.

Malignant nephrosclerosis, microscopic

Malignant hypertension results from endothelial injury and increased permeability to plasma proteins along with platelet activation, leading to firinoid necrosis of small arteries as shown. The damage to this artery is characterized by formation of pink firin—hence the term firinoid. The renin-angiotensin mechanism is stimulated, and very high renin levels develop to produce hypertension. The generation of aldosterone promotes salt retention, which further promotes hypertension. The generation of more renin and angiotensin II leads to further vasoconstriction with ischemic injury.

Cerebral hypertensive hemorrhage, gross

Hypertension is the most common cause of intraparenchymal brain hemorrhage, accounting for more than half of all such bleeds. An intracerebral hemorrhage is one form of stroke. Hemorrhages involving the basal ganglia area as shown here (the putamen in particular) tend to be nontraumatic and caused by chronic hypertension, which damages and weakens the small penetrating arteries. A mass effect from the blood with midline shift, often with secondary edema, may lead to herniation. Hypertensive cerebral hemorrhages originate in the putamen in 50% to 60% of cases, but the thalamus, pons, and cerebellar hemispheres can also be sites of involvement.

Subarachnoid hemorrhage, gross

Berry aneurysms take years to increase in size, and larger aneurysms are more prone to rupture, particularly aneurysms reaching 1 cm in diameter, so that rupture is most likely to occur in young to middle-aged adults. Neurosurgery can be performed with embolization or clipping of the aneurysm at its base to prevent bleeding or rebleeding. The subarachnoid hemorrhage from a ruptured aneurysm is more of an irritant producing vasospasm than a mass lesion. In some cases, this arterial blood under pressure may dissect upward into the brain parenchyma. The result is often a sudden, severe headache followed by loss of consciousness.

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