Glossary

2.2 Mechanisms of Cellular Injury

3 min read•july 24, 2024

Cellular injury is a fundamental concept in understanding disease processes. From to chemical agents, various factors can disrupt cellular function, leading to cascading effects throughout the body. These mechanisms of injury form the basis for many pathological conditions.

Exploring cellular injury reveals how cells respond to stress and damage. Understanding these processes is crucial for grasping how diseases develop and progress, as well as for developing targeted therapeutic approaches to prevent or mitigate cellular damage.

Causes and Mechanisms of Cellular Injury

Causes of cellular injury

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  • Hypoxia starves cells of oxygen disrupts aerobic metabolism often stems from reduced blood flow (), anemia, or respiratory disorders (COPD)

  • Physical agents damage cells through mechanical force (blunt trauma), extreme temperatures (burns, frostbite), or ionizing radiation (X-rays, gamma rays)

  • Chemical agents disrupt cellular processes include environmental toxins (mercury), therapeutic drugs (chemotherapy agents), and pollutants (air particulates)

  • Biological agents invade and harm cells encompass viruses (influenza), bacteria (Streptococcus), parasites (malaria), and fungi (Candida)

Pathophysiology of hypoxic injury

  • Reduced oxygen availability impairs aerobic respiration decreases ATP production forces cells to rely on less efficient anaerobic metabolism

  • Anaerobic metabolism activation increases lactic acid production leads to cellular acidosis disrupts enzyme function and protein structure

  • Ion pump dysfunction occurs as sodium-potassium ATPase fails causes intracellular sodium accumulation results in cell swelling ()

  • Mitochondrial damage disrupts electron transport chain further reduces ATP synthesis compromises cellular energy supply

  • disruption increases intracellular calcium levels activates degradative enzymes (phospholipases, proteases) damages cellular structures

  • Cellular death pathways activate:

    1. initiates in less severe cases controlled
    2. occurs in severe hypoxia uncontrolled cell rupture triggers inflammation

Cellular Injury Mechanisms and Consequences

Free radicals and oxidative stress

  • highly reactive molecules with unpaired electrons produced by normal metabolism (mitochondrial respiration) and environmental factors (UV radiation)

  • occurs when free radical production overwhelms antioxidant defenses damages lipids (cell membranes), DNA (mutations), and proteins (enzyme dysfunction)

  • Antioxidant defense mechanisms protect against oxidative damage:

    • Enzymatic antioxidants neutralize specific free radicals (superoxide dismutase, catalase, glutathione peroxidase)
    • Non-enzymatic antioxidants scavenge various free radicals (vitamin C, vitamin E, glutathione)

  • Cellular adaptations to oxidative stress include upregulating antioxidant enzymes () and increasing synthesis of protective proteins ()

Consequences of cellular damage

  • Membrane damage through increases permeability disrupts selective ion transport alters cellular homeostasis

  • Mitochondrial dysfunction impairs ATP production releases pro-apoptotic factors (cytochrome c) disrupts calcium homeostasis triggers cell death pathways

  • alters structure and function inactivates enzymes forms toxic protein aggregates (amyloid fibrils in Alzheimer's disease)

  • induces mutations (point mutations, deletions) causes strand breaks impairs gene expression affects cell division and protein synthesis

  • Cellular organelle dysfunction:

    • leads to unfolded protein response
    • releases hydrolytic enzymes into cytoplasm

  • Cell death mechanisms activate based on injury severity:

    1. Apoptosis programmed cell death orderly cellular disassembly
    2. Necrosis uncontrolled cell death releases cellular contents triggers inflammation
    3. cellular self-digestion can promote survival or lead to cell death

  • Tissue-level consequences manifest as inflammation (acute or chronic), (excessive scarring), and organ dysfunction (reduced functional capacity)

Key Terms to Review (25)

Apoptosis: Apoptosis is a programmed cell death process that occurs in multicellular organisms, allowing cells to self-destruct when they are damaged, diseased, or no longer needed. This controlled mechanism is crucial for maintaining homeostasis, development, and the elimination of potentially harmful cells, such as those that could become cancerous. By understanding apoptosis, one can appreciate its role in cellular injury, adaptations to stress, and the intricate balance between life and death at the cellular level.
Autophagy: Autophagy is a cellular process that involves the degradation and recycling of cellular components, allowing cells to maintain homeostasis, respond to stress, and remove damaged organelles. This mechanism plays a crucial role in protecting cells from injury, particularly during conditions of nutrient deprivation or cellular stress, by providing energy and building blocks for essential cellular functions.
Biological toxins: Biological toxins are poisonous substances produced by living organisms, such as bacteria, plants, fungi, and animals. These toxins can lead to cellular injury by disrupting normal cellular processes, damaging tissues, or inducing inflammatory responses. Understanding biological toxins is crucial for recognizing how they contribute to disease mechanisms and cellular injury in various medical conditions.
Calcium Homeostasis: Calcium homeostasis refers to the tightly regulated process by which the body maintains stable calcium levels in the blood and within cells. This regulation is crucial for various physiological functions, including muscle contraction, nerve transmission, and blood clotting. Disruption of calcium homeostasis can lead to cellular injury and has significant implications for overall health.
Cell Death: Cell death refers to the process by which cells cease to function and ultimately break down, leading to their demise. This phenomenon can occur through various mechanisms such as apoptosis, necrosis, and autophagy, each having distinct implications for tissue health and disease. Understanding cell death is crucial as it plays a significant role in development, homeostasis, and the response to injury or disease conditions.
Cell Membrane: The cell membrane, also known as the plasma membrane, is a biological barrier that surrounds the cell, separating its internal components from the external environment. This semi-permeable structure plays a crucial role in regulating what enters and exits the cell, maintaining homeostasis, and facilitating communication between cells. Understanding the function and integrity of the cell membrane is essential in the context of cellular injury, as damage to this membrane can lead to significant disruptions in cellular function and viability.
Chemical Injury: Chemical injury refers to cellular damage caused by exposure to harmful substances, including drugs, heavy metals, and industrial chemicals. This type of injury disrupts normal cellular functions, leading to a cascade of biological responses that can result in cell death or dysfunction. Understanding chemical injury is crucial as it highlights the importance of cellular vulnerability to various environmental toxins and the mechanisms through which they exert their damaging effects.
Cytotoxic Edema: Cytotoxic edema refers to the swelling of cells due to the accumulation of intracellular fluid, primarily as a result of cellular injury or dysfunction. This condition often occurs when there is a failure in the mechanisms that regulate ion homeostasis, particularly sodium and potassium, leading to increased intracellular sodium levels, which subsequently draws water into the cells. This type of edema is particularly significant in the context of cell injury, as it can exacerbate cellular damage and impair normal cellular functions.
DNA Damage: DNA damage refers to alterations in the chemical structure of DNA that can impede replication and transcription, ultimately leading to cell injury or death. This damage can occur due to various factors including environmental stressors, radiation, and chemical exposure, which disrupt cellular functions and contribute to disease processes such as cancer and aging.
Endoplasmic Reticulum Stress: Endoplasmic reticulum (ER) stress occurs when the ER experiences an accumulation of misfolded or unfolded proteins, disrupting its normal function. This condition triggers a cellular response known as the unfolded protein response (UPR), which aims to restore homeostasis, but if unresolved, can lead to cell injury and apoptosis. The relationship between ER stress and cellular injury highlights its critical role in various diseases, including neurodegenerative disorders and metabolic syndromes.
Fibrosis: Fibrosis is the excessive accumulation of fibrous connective tissue in an organ or tissue, resulting in scarring and loss of function. It occurs as a response to injury, inflammation, or chronic diseases, leading to the thickening and stiffening of tissues, which can severely affect their normal operation and overall health.
Free Radicals: Free radicals are highly reactive molecules that contain unpaired electrons, which makes them unstable and prone to react with other molecules in the body. Their reactivity can lead to cellular damage by attacking lipids, proteins, and DNA, contributing to various diseases and aging processes. Understanding free radicals is crucial in exploring mechanisms of cellular injury, as they play a significant role in oxidative stress and inflammation.
Functional Impairment: Functional impairment refers to a reduction in an individual’s ability to perform daily activities or tasks, often resulting from physiological, psychological, or neurological conditions. This term is crucial for understanding how injuries or diseases can affect a person's overall quality of life, particularly in the context of cellular injury and nervous system disorders, where the ability to carry out normal functions may be significantly hindered.
Heat Shock Proteins: Heat shock proteins (HSPs) are a group of proteins that are produced by cells in response to stressful conditions, such as heat, toxins, or injury. They function primarily as molecular chaperones, helping to stabilize and refold misfolded proteins, preventing protein aggregation, and aiding in cellular repair processes. Their critical role in cellular response to stress links them to mechanisms of cellular injury and recovery.
Hypoxia: Hypoxia refers to a deficiency in the amount of oxygen reaching the tissues, which can lead to cellular injury and dysfunction. It plays a significant role in various health conditions, as inadequate oxygen supply can result in impaired cellular metabolism, anaerobic respiration, and the eventual death of cells. Understanding hypoxia is crucial for grasping how it contributes to brain injuries and disorders related to red blood cells.
Inflammatory response: The inflammatory response is a biological reaction of the body to harmful stimuli, such as pathogens, damaged cells, or irritants. It serves as a protective mechanism that helps isolate and eliminate the source of injury, facilitating healing and restoration. This complex process involves various immune cells, signaling molecules, and blood vessels, leading to redness, swelling, heat, and pain at the affected site, which are all indicators of inflammation.
Ischemia: Ischemia refers to the inadequate blood supply to a tissue, resulting in a deficiency of oxygen and nutrients necessary for cellular metabolism. This condition can lead to cellular injury and can have widespread implications for organ function and overall health.
Lipid peroxidation: Lipid peroxidation is a process in which free radicals attack lipids containing carbon-carbon bonds, resulting in the degradation of these lipids. This process can lead to cell membrane damage and is associated with various forms of cellular injury, contributing to conditions like oxidative stress and inflammation. Understanding lipid peroxidation is crucial as it plays a significant role in cellular damage mechanisms that can result from various insults such as toxins, radiation, and ischemia.
Lysosomal membrane permeabilization: Lysosomal membrane permeabilization (LMP) is a process in which the membranes of lysosomes become disrupted, leading to the release of their hydrolytic enzymes into the cytosol. This event can contribute to cellular injury by causing a cascade of damage, including cellular apoptosis and necrosis, which is particularly relevant in various pathophysiological conditions.
Mitochondria: Mitochondria are known as the powerhouses of the cell, responsible for generating adenosine triphosphate (ATP) through cellular respiration. They play a crucial role in energy production and also have key functions in regulating metabolism, apoptosis, and calcium homeostasis, making them essential for cellular health and function.
Necrosis: Necrosis is the process of uncontrolled cell death caused by factors such as infection, injury, or lack of blood flow. This type of cell death often leads to inflammation and can affect surrounding tissues, making it a key concept in understanding how cells respond to various stresses and injuries.
Nrf2 pathway: The nrf2 pathway is a cellular signaling mechanism that regulates the expression of antioxidant proteins and detoxifying enzymes in response to oxidative stress and electrophilic stress. This pathway plays a critical role in protecting cells from injury by activating genes that combat reactive oxygen species (ROS) and other harmful compounds, thus promoting cellular health and survival.
Oxidative Stress: Oxidative stress refers to a condition in which there is an imbalance between the production of reactive oxygen species (ROS) and the body’s ability to detoxify these harmful compounds or repair the resulting damage. This imbalance can lead to cellular injury and contributes significantly to various diseases and aging processes, making it essential to understand in relation to mechanisms of cellular injury and adaptations to stress.
Protein Denaturation: Protein denaturation is the process in which proteins lose their three-dimensional structure and functionality due to the disruption of non-covalent interactions that maintain their shape. This alteration in structure can result from various stressors, including changes in temperature, pH, and exposure to chemicals. When proteins denature, they may become nonfunctional, impacting cellular processes and leading to cellular injury.
Reactive Oxygen Species: Reactive oxygen species (ROS) are highly reactive molecules containing oxygen, such as free radicals and peroxides, that can damage cellular components. They are produced as byproducts of normal cellular metabolism, especially in the mitochondria, and play a dual role in cell signaling and promoting oxidative stress, which can lead to various mechanisms of cellular injury.
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