Frailty and Cellular Adaptation: A Summary Review PDF

## Frailty Frailty is a state of increased vulnerability to poor resolution of homeostasis following a stress, which increases the risk of adverse outcomes including falls, delirium, disability, long-term care, and death. * **Pathophysiology:** Frailty includes many interrelated physiological syst...

## Frailty Frailty is a state of increased vulnerability to poor resolution of homeostasis following a stress, which increases the risk of adverse outcomes including falls, delirium, disability, long-term care, and death. * **Pathophysiology:** Frailty includes many interrelated physiological systems. * **Aging:** Frailty includes many interrelated physiological systems. A gradual decline progresses with aging, but in frailty this decline becomes accelerated. Homeostatic mechanisms begin to fail, and vulnerability becomes accentuated. * **Stress:** Even minor changes in health status after a relatively minor stressor event can cause a sudden, often serious health status change. ### Factors Influencing Frailty * **Genetic factors:** Genetic and epigenetic mechanisms and environmental factors regulate differential expression of genes in cells. * **Environmental factors:** Factors that are especially important in aging include brain and endocrine, immune, hematopoietic, and skeletal muscle systems. ### Cumulative Molecular and Cellular Damage * **Reduced physiological reserve:** * Brain * Endocrine * Immune * Skeletal muscle * Cardiovascular * Respiratory * Renal * **Physical activity** * **Nutritional factors** ### Progressive Levels of Frailty * **Frailty:** * Falls * Delirium * Fluctuating disability * **Increased care needs** * **Admission to hospital** * **Admission to long-term care** ### Somatic Death * **Somatic death:** Death of the entire person. * **Postmortem change:** Unlike cellular death in a live body, it is diffuse, unlike the changes that follow cellular death in a live body, and does not involve the inflammatory response. * **Signs of postmortem change:** * **Respiration and circulation**: Cessation within minutes of death. * **Skin Color**: Pale and yellowish, but cheeks and lips may persist in cases like carbon monoxide poisoning, drowning, and chloroform poisoning. * **Temperature:** Falls immediately and then more rapidly for about 24 hours. * **Body Stiffening:** Muscle stiffening, or rigor mortis, develops within 6 hours. * **Putrefaction:** Foul-smelling decay that generally becomes obvious 24 to 48 hours after death * **Postmortem Autolysis:** Lytic dissolution of cells. ### Cellular Adaptation * **Injury**: Cellular injury leads to tissue and organ injury and can be reversible or irreversible. * **Adaptation:** Allows cells to maintain a steady state despite adverse conditions. * **Types of adaptation:** * **Atrophy:** Decrease in cell size that is most common in skeletal muscle, the heart, secondary sex organs, and the brain. * **Hypertrophy:** Increase in cell size due to increased workload or hormonal stimulation * **Hyperplasia:** An increase in the number of cells due to increased rate of cellular division. * **Metaplasia:** Reversible replacement of one mature cell type by another. It is associated with tissue damage and regeneration. * **Dysplasia:** Abnormal changes in cell size, shape, and organization. It is not cancer but progresses to cancer. ### Cellular injury * **Causes:** * Lack of oxygen (hypoxia) * Free radicals * Chemical toxins * Infectious agents * Unintentional or intentional injury * Inflammatory and immune responses * Genetics * Insufficient nutrients * Physical trauma * **Types:** * Acute or chronic * Reversible or irreversible * **Processes:** * Necrosis * Apoptosis * Autophagy * Accumulation * Pathological calcification * **Biochemical themes:** * Depletion of ATP * Decreased levels of oxygen and increased levels of oxygen-derived free radicals * Increased concentration of intracellular calcium * Defects in membrane permeability * **Cell death pathways:** * Decreased ATP production * Failure of active transport mechanisms * Cellular swelling * Detachment of ribosomes from the endoplasmic reticulum * Cessation of protein synthesis * Mitochondrial swelling * Vacuolation * Leakage ### Summary Review * **Hypoxic Injury:** The initial insult is usually ischemia, causing a cessation of blood flow to vessels that supply the cell with oxygen and nutrients. * **Reperfusion Injury:** Restoration of oxygen after ischemic injury results in reperfusion (reoxygenation) injury. * **Reactive Oxygen Species (ROS):** Metabolic byproducts of aerobic metabolism that can play a crucial biological role in diseases, but also in cellular communication and cell function. * **Free Radicals:** Free radicals cause cellular damage, particularly ROS, and are an important mechanism in many conditions including chemical and radiation injury, ischemia-reperfusion injury, microbial killing by phagocytes, and cellular aging. * **Oxidative Stress:** Significant mechanism of membrane damage. * **Chemical and Toxic Injury:** Initial insult is damage or destruction of the plasma membrane. * **Air pollution:** The world's largest single environmental health risk. * **Heavy Metals:** Commonly associated with harmful effects in humans. * **Unintentional and Intentional Injuries:** A significant health problem. * **Microorganisms:** Can invade and destroy cells, produce toxins, and cause damaging hypersensitivity reactions. * **Inflammation:** Involves powerful biochemicals and proteins capable of damaging cells. * **Genetic Disorders:** Can damage cells by altering the nucleus and the plasma membrane’s structure, shape, receptors, or transport mechanisms. * **Nutritional Deprivation:** Can cause cell injury by altering cellular structure and function. * **Physical Agents:** Include temperature extremes, changes in atmospheric pressure, ionizing radiation, illumination, mechanical stresses, and noise. ### Manifestations of Cellular Injury * **Cellular Swelling:** The accumulation of excessive water in the cell is a sign of many types of cellular injury. * **Accumulation of Organic Substances:** This includes lipids, carbohydrates, glycogen, proteins, and pigments. * **Dystrophic Calcification:** Accumulation of calcium salts in injured or dead cells. ### Aging * **Changes of Aging:** Hallmarks include accumulation of damaged macromolecules. * **Origins of Aging:** Genetic, epigenetic, inflammatory, oxidative stress, cell renewal by adult stem cells, and metabolic and endocrine origins. * **Senescence:** Permanent proliferative arrest of cells in response to various stressors that may be an important contributor to aging and age-related diseases. * **Inflammaging:** Increased levels of circulating cytokines and proinflammatory markers. * **Microbiota:** Plays a fundamental role in the induction and function of the immune system. * **Diet:** Has a major influence on both the development and the prevention of age-related diseases. * **Maximal Life Span:** Dictated by currently unknown intrinsic mechanisms. * **Life Expectancy:** In the United States, there is a trend of decreasing life expectancy. * **Frailty:** A common clinical syndrome in older adults characterized by vulnerability to falls, functional decline, disability, disease, and death. * **Risk Factors:** Involves oxidative stress, dysregulation of inflammatory cytokines and hormones, malnutrition, physical inactivity, and muscle changes. ### Somatic Death * **Definition:** Death of the entire organism. * **Postmortem Change:** Does not involve the inflammatory response. * **Signs of Somatic Death:** * Cessation of respiration and circulation * Gradual lowering of body temperature * Dilation of pupils * Loss of elasticity and transparency in the skin * Stiffening of muscles (rigor mortis) * Discoloration of the skin (livor mortis) * Signs of putrefaction are obvious about 24 to 48 hours after death.