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Terms in this set (73)

Myofibril relaxation is an early sign of reversible injury in cardiac myocytes, which occurs within the first 30 minutes of severe ischemia. Myofibril relaxation corresponds with intracellular ATP depletion and lactate accumulation due to anaerobic glycolysis during this period.

Disaggregation of polysomes denotes the dissociation of rRNA from mRNA in reversible ischemic/hypoxic injury. Depletion of intracellular ATP is thought to promote the dissolution of polysomes into monosomes as well as the detachment of ribosomes from the rough endoplasmic reticulum. Disaggregation of polysomes results in impaired protein synthesis.

Disaggregation of granular and fibrillar elements of the nucleus is associated with reversible cell injury. Another common nuclear change associated with reversible cell injury is clumping of nuclear chromatin, perhaps secondary to a decrease in intracellular pH.

Triglyceride droplet accumulation is characteristic of reversible cell injury, especially in hepatocytes, and also in striated muscle cells and renal cells. This fatty change may result from the decreased synthesis of intracellular proteins that occurs with cell injury. In the hepatocyte, decreased production of lipid acceptor proteins prevents the normal incorporation of triglycerides into lipoproteins. Since triglycerides cannot be rapidly exported from the cell in the form of lipoproteins, they accumulate intracellularly.

Glycogen loss is another early and reversible cellular response to injury. As a result of lowered mitochondrial ATP production, ATP must be supplied to the cell via anaerobic glycolysis of glucose derived from the cell's glycogen stores. Myocardial glycogen stores may be completely depleted within 30 minutes of the onset of severe ischemia.
area of residence
This man with a large area of localized cardiac apical wall thinning likely died of chronic Chagas cardiomyopathy. Chagas disease is caused by infection with the protozoan Trypanosoma cruzi, which is transmitted by the triatomine "kissing" bug (Reduviid family) found throughout the Americas as far north as the southern United States. Infection is rare in developed regions, but the disease is endemic throughout Central and South America where widespread open-air and thatched-roof housing exposes individuals to routine contact with the triatomine vector.

Years following initial infection, some individuals develop serious end-organ damage affecting the cardiac, gastrointestinal, and/or central nervous systems. Cardiac disease results from a chronic parasite-induced and immune-mediated myocarditis that leads to dilated cardiomyopathy (DCM). Chronic Chagas cardiomyopathy is relatively unique among DCMs in that there is characteristically localized apical wall thinning with the development of a large apical aneurysm. In addition to impairing ventricular systolic function, the aneurysm can harbor mural thrombus that may systemically embolize and cause stroke. Damage to the cardiac conduction system can also trigger ventricular arrhythmias (eg, ventricular tachycardia, ventricular fibrillation) that can lead to sudden cardiac death (the likely cause of death in this man).
The gastrointestinal manifestations of Chagas disease involve destruction of the myenteric plexus, which can lead to progressive dilation and dysfunction of the esophagus and, less commonly, the colon.
This patient's presentation is consistent with coronary artery atherosclerosis. The pathogenesis of atherosclerosis likely begins with 1) endothelial cell injury. Chronic endothelial cell injury may result from hypertension (and related hemodynamic factors), hyperlipidemia, smoking, and diabetes mellitus. Such injury leads to endothelial cell dysfunction and/or exposure of subendothelial collagen (endothelial cell denudation).
Endothelial cell dysfunction results in monocyte and lymphocyte adhesion and migration into the intima while exposure of subendothelial collagen promotes platelet adhesion. Growth factors produced by monocytes and platelets stimulate medial smooth muscle cell (SMC) migration into the intima.

At the same time, increased vascular permeability allows LDL cholesterol into the intima, where it is phagocytosed by the accumulating macrophages and SMCs to produce lipid-laden foam cells (fatty streak).
The continued release of cytokines and growth factors results in a chronic inflammatory state within the underlying intima. This promotes further deposition of LDL cholesterol within the intima and stimulates SMC proliferation with increased production of collagen and proteoglycans. Necrosis of foam cells results in release of toxic oxidized LDL into the extracellular matrix, perpetuating a cycle of injury. The lesion eventually organizes into a core of lipid debris surrounded by monocytes and lymphocytes covered by a fibrous cap with intermixed SMCs (fibrofatty atheroma).