Growth Adaptations, Cellular Injury, and Cell Death PDF

Www.Medicalstudyzone.com Growth GrowthAdaptations, Adaptations,Cellular Cellular Injury, Injury,and CellDeath andCell Death...

Www.Medicalstudyzone.com Growth GrowthAdaptations, Adaptations,Cellular Cellular Injury, Injury,and CellDeath andCell Death 11 GROWTH ADAPTATIONS I. BASIC PRINCIPLES A. An organ is in homeostasis with the physiologic stress placed on it. B. An increase, decrease, or change in stress on an organ can result in growth adaptations. IL HYPERPLASIA AND HYPERTROPHY A. An increase in stress leads to an increase in organ size. 1. Occurs via an increase in the size (hypertrophy) and/or the number (hyperplasia) of cells B. Hypertrophy involves gene activation, protein synthesis, and production of organelles. C. Hyperplasia involves the production of new cells from stem cells. D. Hyperplasia and hypertrophy generally occur together (e.g., uterus during pregnancy). 1. Permanent tissues (e.g., cardiac muscle, skeletal muscle, and nerve), however, cannot make new cells and undergo hypertrophy only. 2. For example, cardiac myocytes undergo hypertrophy, not hyperplasia, in response to systemic hypertension (Fig. 1.1). E. Pathologic hyperplasia (e.g., endometrial hyperplasia) can progress to dysplasia and, eventually, cancer. 1. A notable exception is benign prostatic hyperplasia (BPH), which does not increase the risk for prostate cancer. III. ATROPHY A. A decrease in stress (e.g., decreased hormonal stimulation, disuse, or decreased nutrients/blood supply) leads to a decrease in organ size (atrophy). 1. Occurs via a decrease in the size and number of cells B. Decrease in cell number occurs via apoptosis. C. Decrease in cell size occurs via ubiquitin-proteosome degradation of the cytoskeleton and autophagy of cellular components. 1. In ubiquitin-proteosome degradation, intermediate filaments of the cytoskeleton are "tagged" with ubiquitin and destroyed by proteosomes. 2. Autophagy of cellular components involves generation of autophagic vacuoles. These vacuoles fuse with lysosomes whose hydrolytic enzymes breakdown cellular components. IV. METAPLASIA A. A change in stress on an organ leads to a change in cell type (metaplasia). 1. Most commonly involves change of one type of surface epithelium (squamous, columnar, or urothelial) to another 2. Metaplastic cells are better able to handle the new stress. B. Barrett esophagus is a classic example. pathoma.com 1  Www.Medicalstudyzone.com 2 FUNDAMENTALS OF PATHOLOGY 1. Esophagus is normally lined by nonkeratinizing squamous epithelium (suited to handle friction of a food bolus). 2. Acid reflux from the stomach causes metaplasia to nonciliated, mucin-producing columnar cells (better able to handle the stress of acid, Fig. 1.2). C. Metaplasia occurs via reprogramming of stem cells, which then produce the new cell type. 1. Metaplasia is reversible, in theory, with removal of the driving stressor. 2. For example, treatment of gastroesophageal reflux may reverse Barrett esophagus. D. Under persistent stress, metaplasia can progress to dysplasia and eventually result in cancer. 1. For example, Barrett esophagus may progress to adenocarcinoma of the esophagus. 2. A notable exception is apocrine metaplasia of breast, which carries no increased risk for cancer. E. Vitamin A deficiency can also result in metaplasia. 1. Vitamin A is necessary for differentiation of specialized epithelial surfaces such as the conjunctiva covering the eye. 2. In vitamin A deficiency, the thin squamous lining of the conjunctiva undergoes metaplasia into stratified keratinizing squamous epithelium. This change is called keratomalacia (Fig. 1.3). F. Mesenchymal (connective) tissues can also undergo metaplasia. 1. A classic example is myositis ossificans in which connective tissue within muscle changes to bone during healing after trauma (Fig. 1.4). V. DYSPLASIA A. Disordered cellular growth B. Most often refers to proliferation of precancerous cells 1. For example, cervical intraepithelial neoplasia (CIN) represents dysplasia and is a precursor to cervical cancer. C. Often arises from longstanding pathologic hyperplasia (e.g., endometrial hyperplasia) or metaplasia (e.g., Barrett esophagus) D. Dysplasia is reversible, in theory, with alleviation of inciting stress. 1. If stress persists, dysplasia progresses to carcinoma (irreversible). VI. APLASIA AND HYPOPLASIA A. Aplasia is failure of cell production during embryogenesis (e.g., unilateral renal agenesis). B. Hypoplasia is a decrease in cell production during embryogenesis, resulting in a relatively small organ (e.g., streak ovary in Turner syndrome). Fig. 1.1 Left ventricular hypertrophy. (Courtesy of Fig.1.2 Barrett esophagus. Aliya Husain, MD)