Liver Regeneration Study Resources

Chapter 4: Cellular Biology This chapter explores altered cellular and tissue biology, focusing on cellular adaptation, injury, manifestations of cellular injury, cellular death, aging, and the various types of cell death such as necrosis and apoptosis. Cellular adaptation allows cells to respond to physiological and pathological conditions, but severe or prolonged stressors can lead to cellular injury or death. Common sources of cell injury include lack of oxygen, free radicals, infections, inflammation, and metabolic derangements. Cellular aging also contributes to changes in structure and function. Bullet points Liver regeneration ● Removal of part of the liver triggers rapid hyperplasia of the remaining liver cells ● Regeneration is complete in about 2 weeks, even with removal of 70% of liver mass ● Compensatory hyperplasia can also occur in other organs such as the epidermal and intestinal epithelia, bone marrow cells, and fibroblasts ● Loss of cells within an organ stimulates DNA synthesis, mitotic division, and hyperplasia ● Hyperplasia can also occur in bone, cartilage, and smooth muscle cells Hormonal hyperplasia ● Occurs in organs that respond to endocrine hormonal stimulation ● For example, estrogen secretion during the menstrual cycle leads to hyperplasia and proliferation of the endometrium ● Hormonal secretion from various endocrine organs maintains the normal structure and function of target organs ● Pathologic hormonal hyperplasia is the abnormal proliferation of normal cells due to excessive hormonal stimulation or growth factors ● Examples include pathologic hyperplasia of the uterine endometrium and benign prostatic hyperplasia (BPH) Dysplasia ● Refers to abnormal changes in the size, shape, and organization of mature cells ● Not considered a true adaptive process, but related to hyperplasia and is often called atypical hyperplasia ● Common in epithelial tissue of the uterine cervix, endometrium, and gastrointestinal and respiratory tract mucosa ● Dysplasia can be reversible if the triggering stimulus is removed ● If dysplastic changes penetrate the basement membrane, it is considered an invasive neoplasm Metaplasia ● Metaplasia is the reversible replacement of one mature cell type with another cell type ● It occurs in response to tissue damage, repair, and regeneration ● Metaplasia can be an adaptive response, but often the change is not beneficial ● For example, chronic irritation from smoking can cause the replacement of normal ciliated columnar epithelial cells with stratified squamous epithelial cells Cellular Injury ● Cellular injury occurs when a cell is unable to maintain homeostasis ● Injury can be reversible or irreversible ● Causes of cellular injury include chemical agents, lack of oxygen, infectious agents, physical factors, immunologic reactions, genetic factors, and nutritional imbalances Types of Progressive Cell Injury and Responses ● Adaptation: atrophy, hypertrophy, hyperplasia, metaplasia ● Active cell injury: loss of ATP, cellular swelling, detachment of ribosomes ● Necrosis: severe cell swelling and breakdown of organelles ● Apoptosis: programmed cell death for elimination of unwanted cell populations ● Autophagy: self-eating of cytoplasmic vesicles and organelles ● Chronic cell injury: persistent stimuli may involve specific organelles or cytoskeleton ● Accumulations or infiltrations: water, pigments, lipids, glycogen, proteins ● Pathologic calcification: dystrophic and metastatic calcification Stages of Cellular Adaptation, Injury, and Death ● Normal cell responds to physiological and pathological stresses by adapting ● Cell injury occurs if adaptive responses are exceeded or compromised ● Injury can be reversible if it is mild or transient, but if the stimulus persists, irreversible injury and cell death occur ● The extent of cellular injury depends on cell type and level of stress Cell Injury and Death ● Cell injury can occur due to various factors such as nature, severity, and duration of the injury ● Fully differentiated, mature cells are more susceptible to injury than cell precursors ● Individual differences like genetics, nutritional status, and immunologic competency can influence the extent of cell injury ● Irreversible injury and cell death occur when changes to the nucleus or disruption of cell membranes happen General Mechanisms of Cell Injury ● Cell injury and death involve biochemical events like ATP depletion, damage from free radicals, and alterations in calcium level ● Injury to cell components includes membrane damage, protein folding defects, mitochondrial compromise, and DNA damage ● Common forms of cell injury include ischemic/hypoxic injury, ischemiareperfusion injury, oxidative stress, and chemical injury Ischemic and Hypoxic Injury ● Hypoxia, or lack of sufficient oxygen, is the most common cause of cellular injury ● Causes of hypoxia include reduced oxygen content, loss of hemoglobin, decreased RBC production, respiratory and cardiovascular diseases, and poisoning of oxidative enzymes ● Hypoxia negatively impacts normal physiologic processes and triggers the production of reactive oxygen species (ROS)