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Questions and Answers
Which condition is directly characterized by cell swelling and organellar breakdown?
Which condition is directly characterized by cell swelling and organellar breakdown?
What factor does NOT contribute to cell injury?
What factor does NOT contribute to cell injury?
Which system is NOT considered inherently vulnerable to cell injury?
Which system is NOT considered inherently vulnerable to cell injury?
Which type of cell death occurs under normal physiological conditions?
Which type of cell death occurs under normal physiological conditions?
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What is primarily affected by hypoxia in relation to cell injury?
What is primarily affected by hypoxia in relation to cell injury?
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What mechanism leads to the influx of calcium in ischemic conditions?
What mechanism leads to the influx of calcium in ischemic conditions?
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Which nutritional imbalance is strongly linked to the pathogenesis of atherosclerosis?
Which nutritional imbalance is strongly linked to the pathogenesis of atherosclerosis?
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All of the following are considered possible physical agents of cell injury EXCEPT:
All of the following are considered possible physical agents of cell injury EXCEPT:
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Which condition is NOT a cause of hypercalcæmia?
Which condition is NOT a cause of hypercalcæmia?
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Which type of cellular adaptation is characterized by an increase in cell size due to increased protein synthesis?
Which type of cellular adaptation is characterized by an increase in cell size due to increased protein synthesis?
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What is a characteristic feature of metaplasia?
What is a characteristic feature of metaplasia?
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In which tissue does metastatic calcification most commonly occur?
In which tissue does metastatic calcification most commonly occur?
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What type of hyperplasia occurs when a portion of tissue is removed or is diseased?
What type of hyperplasia occurs when a portion of tissue is removed or is diseased?
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What is a common biochemical change associated with atrophy?
What is a common biochemical change associated with atrophy?
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Which of the following cell adaptations allows cells to modulate their environment to escape injury?
Which of the following cell adaptations allows cells to modulate their environment to escape injury?
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Which condition does NOT typically cause significant impairment of organ function despite extensive deposition?
Which condition does NOT typically cause significant impairment of organ function despite extensive deposition?
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What is the primary consequence of reduced intracellular ATP during hypoxic injury?
What is the primary consequence of reduced intracellular ATP during hypoxic injury?
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Which of the following is a hallmark of irreversible cellular injury?
Which of the following is a hallmark of irreversible cellular injury?
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How do free radicals contribute to cellular aging?
How do free radicals contribute to cellular aging?
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What is the mechanism by which mercury causes chemical injury in cells?
What is the mechanism by which mercury causes chemical injury in cells?
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Which cellular component is primarily affected by free radical-induced lipid peroxidation?
Which cellular component is primarily affected by free radical-induced lipid peroxidation?
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What is the result of anaerobic glycolysis during acute hypoxia?
What is the result of anaerobic glycolysis during acute hypoxia?
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Which process leads to the formation of myelin figures in dead cells?
Which process leads to the formation of myelin figures in dead cells?
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What role do neutrophils play after reperfusion of ischemic tissue?
What role do neutrophils play after reperfusion of ischemic tissue?
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What change in cellular morphology is typically seen in necrosis?
What change in cellular morphology is typically seen in necrosis?
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Which of the following would primarily indicate a state of irreversible injury?
Which of the following would primarily indicate a state of irreversible injury?
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What type of necrosis is characterized by the preservation of the structural outlines of dead cells?
What type of necrosis is characterized by the preservation of the structural outlines of dead cells?
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Which mechanism primarily leads to cellular injury from chemical toxins?
Which mechanism primarily leads to cellular injury from chemical toxins?
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What effect does hypoxia have on the plasma membrane sodium pump?
What effect does hypoxia have on the plasma membrane sodium pump?
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Which of the following is true regarding the effect of oxygen free radicals on DNA?
Which of the following is true regarding the effect of oxygen free radicals on DNA?
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What is the primary mechanism by which cells are removed during coagulative necrosis?
What is the primary mechanism by which cells are removed during coagulative necrosis?
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Which of the following types of necrosis is characterized by the presence of a cheesy, white gross appearance due to tuberculous infection?
Which of the following types of necrosis is characterized by the presence of a cheesy, white gross appearance due to tuberculous infection?
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What physiological process is indicated by a cell exhibiting shriveling, nuclear chromatin condensation, and formation of apoptotic bodies?
What physiological process is indicated by a cell exhibiting shriveling, nuclear chromatin condensation, and formation of apoptotic bodies?
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Which stimulus does NOT initiate apoptosis?
Which stimulus does NOT initiate apoptosis?
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What type of necrosis occurs primarily due to focal bacterial or fungal infections resulting in the accumulation of white cells?
What type of necrosis occurs primarily due to focal bacterial or fungal infections resulting in the accumulation of white cells?
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Which category of intracellular accumulation is characterized by a normal endogenous substance produced at an inadequate metabolic rate?
Which category of intracellular accumulation is characterized by a normal endogenous substance produced at an inadequate metabolic rate?
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In which condition would you most likely observe fat necrosis?
In which condition would you most likely observe fat necrosis?
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What type of necrosis is typically associated with ischemic coagulative necrosis and may include a superimposed infection?
What type of necrosis is typically associated with ischemic coagulative necrosis and may include a superimposed infection?
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What is the main cellular characteristic observed in glycogen accumulation?
What is the main cellular characteristic observed in glycogen accumulation?
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Hemorrhagic necrosis resulting from ischemic injury leading to cell death is primarily witnessed in which organ?
Hemorrhagic necrosis resulting from ischemic injury leading to cell death is primarily witnessed in which organ?
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What is the consequence of apoptosis that differentiates it from necrosis?
What is the consequence of apoptosis that differentiates it from necrosis?
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Which pigment accumulation is caused by an excess of iron in tissues and appears golden brown?
Which pigment accumulation is caused by an excess of iron in tissues and appears golden brown?
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The process of dystrophic calcification occurs in which circumstance?
The process of dystrophic calcification occurs in which circumstance?
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Xanthomas are primarily associated with the accumulation of which type of substances in macrophages?
Xanthomas are primarily associated with the accumulation of which type of substances in macrophages?
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Study Notes
Cell Injury
- When cells encounter physiological stresses or pathological stimuli, they can undergo adaptation to preserve viability.
- If the cell's adaptive capability is exceeded, cell injury develops.
- There are two main patterns of cell death: necrosis and apoptosis.
- Necrosis is caused by noxious conditions and characterized by cell swelling, protein denaturation, and organellar breakdown.
- Apoptosis is a programmed cell death that occurs in normal or physiological conditions.
Causes of Cell Injury
- Hypoxia impinges on aerobic oxidative respiration and should be distinguished from ischemia, which also results in hypoxic cell injury.
- Physical agents, including trauma, extremes of temperatures, radiation, electric shock, and sudden changes in atmospheric pressure.
- Chemicals and drugs can cause cell injury by altering membrane permeability, osmotic homeostasis, or the integrity of enzyme cofactors.
- Microbiologic agents, ranging from viruses to tapeworms.
- Immunologic reactions, such as anaphylactic reactions.
- Genetic defects, including Down's syndrome and sickle cell anemia.
- Nutritional imbalances, such as protein-calorie insufficiency, vitamin deficiencies, and diets rich in animal fat.
- Aging.
Mechanisms of Cell Injury
- Four intracellular systems are vulnerable to injury: cell membrane integrity, aerobic respiration, protein synthesis, and the genetic apparatus.
- Cytosolic free calcium is maintained at extremely low levels by ATP-dependent calcium transporters.
- Mitochondria and endoplasmic reticulum contain a higher concentration of calcium.
- Ischemia or toxins allow an influx of calcium from the extracellular space and a release of mitochondrial calcium, resulting in the activation of various enzymes, including phospholipases, proteases, ATPases, and endonucleases.
- Oxygen free radicals are important mediators of cell death.
Ischemic and Hypoxic Injury
- Reversible injury affects aerobic respiration, resulting in reduced intracellular ATP, influx of extracellular calcium, reduction of the plasma membrane sodium pump with accumulation of intracellular sodium and diffusion of potassium out of the cell, and osmotic water accumulation leading to acute cellular swelling.
- Irreversible injury features: severe vacuolization of mitochondria and accumulation of calcium particles, extensive damage of the plasma membrane, swelling of lysosomes, calcium-mediated injury due to reperfusion of oxygen, continued loss of proteins, coenzymes, and RNA, and leak of lysosomal enzymes into the cytoplasm leading to degradation of cytoplasmic components.
Mechanisms of Irreversible Injury
- Progressive loss of membrane phospholipids.
- Cytoskeletal abnormalities due to activation of proteases and increased calcium.
- Toxic oxygen radicals generated after reperfusion of the ischemic area released by influxed neutrophils.
- Lipid breakdown products have detergent effects.
Free Radical Mediation of Cell Injury
- Free radicals are implicated in chemical and radiation-mediated injury, oxygen toxicity, cellular aging, microbial killing, inflammatory damage, and tumor killing.
- Free radicals are chemical species with a single unpaired electron in an outer orbital and are highly reactive.
- They may be generated within the cell by absorption of radiant energy, reduction-oxidation reactions, and enzymatic catabolism of oxygenous chemicals.
- Oxygen free radicals react with lipid peroxidation of plasma membranes, deoxyribonucleic acid (DNA), and cross-linking of proteins.
Chemical Injury
- Two main mechanisms of chemical injury: combining with a critical molecular component or cellular organelle, such as mercury binding to sulfhydryl groups of the cell membrane and other proteins, and conversion to reactive toxic metabolites, often by P-450 oxidases in the SER.
- Carbon tetrachloride (CCl4) is converted to the toxic free radical CCl3., causing autocatalytic membrane peroxidation and rapid breakdown of endoplasmic reticulum.
Patterns of Acute Cell Injury
- Reversible cell injury involves cellular swelling (hydropic changes), cytoplasmic eosinophilia due to cytoplasmic acidosis and loss of ribosomes, and fatty change.
- Ultrastructural changes include plasma membrane blebbing, distortion of microvilli, loosening of intercellular attachments, mitochondrial swelling and appearance of phospholipids rich amorphous densities, dilatation of endoplasmic reticulum, detachment of ribosomes, dissociation of polysomes, and nuclear alterations.
Necrosis
- Necrosis is a sequence of morphologic changes following cell death in living tissue and is characterized by enzymatic digestion of the cell and denaturation of proteins.
- Cytoplasmic changes include eosinophilia and glassy appearance due to loss of glycogen, cytoplasmic vacuolation, and calcification.
- Nuclear changes include karyolysis, pyknosis, and karyorrhexis.
Types of Necrosis
- Coagulative necrosis preserves the structural outlines of the coagulated cell or tissue for days.
- Liquefactive necrosis is caused by focal bacterial or fungal infection.
- Gangrenous necrosis refers to ischemic coagulative necrosis with superimposed infection and liquifactive necrosis.
- Caseous necrosis is seen in tuberculous infection.
- Fat necrosis describes focal areas of fat destruction following acute pancreatitis.
Apoptosis
- Apoptosis is responsible for programmed cell death in physiological and pathological conditions.
- It involves single cells or clusters of cells and appears as round masses on H&E stained sections.
- The nucleus condenses and aggregates peripherally under the nuclear membrane.
- The cell shrinks, forms cytoplasmic buds, and fragments into apoptotic bodies.
- Apoptosis does not elicit an inflammatory response.
- Apoptosis is initiated by withdrawal of growth factors or hormones, engagement of specific receptors, injury by radiation, toxins, and free radicals, and intrinsic protease activation.
Intracellular Accumulations
- Normal cells may accumulate abnormal substances, either transiently or permanently.
- Intracellular accumulation can be subdivided into three categories: normal endogenous substance produced at a normal or increased rate, normal or abnormal endogenous substance which can not be metabolized, and abnormal exogenous substance deposit.
Fatty Change (Steatosis)
- Steatosis is an abnormal accumulation of triglycerides within parenchymal cells.
- It is most often seen in the liver and is reversible.
- It may be caused by toxins, diabetes mellitus, protein malnutrition, obesity, and anoxia.
Cholesterol and Cholesterol Esters
- Macrophages in contact with lipid debris of necrotic cells may become filled with lipid.
- In atherosclerosis, smooth muscle cells and macrophages are filled with lipid vacuoles.
- Xanthomas are accumulations of fat within macrophages of subcutaneous connective tissues.
Proteins
- Accumulate in proximal convoluted tubules in cases of glomerular diseases with proteinuria.
Glycogen
- Accumulate in cases of abnormal metabolism of glucose or glycogen.
Pigments
- Pigments are colored substances.
- Melanin accumulates in basal cells of the epidermis.
- Hemosiderin is a hemoglobin-derived granular pigment that accumulates in tissues when there is local or systemic excess iron.
Pathologic Calcification
- Dystrophic calcification is the deposition of calcium salts in dead or dying tissues, independent of serum calcium levels or calcium metabolic derangement.
- Metastatic calcification occurs in normal tissues when there is hypercalcemia, often caused by primary endocrine dysfunction, tumors, ingested exogenous substances, sarcoidosis, or advanced renal failure.
Cellular Adaptations of Growth and Differentiation
- Atrophy is shrinkage in the size of the cell by loss of cell substance.
- Hypertrophy is an increase in the size of cells by increased synthesis of structural proteins and organelles.
- Hyperplasia is an increase in the number of cells in an organ or tissue.
- Metaplasia is a reversible change in which one adult cell type is replaced by another adult cell type.
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Description
Explore the mechanisms and causes of cell injury in this quiz. Understand the differences between necrosis and apoptosis, as well as the various physiological and pathological stimuli that can lead to cellular damage. Test your knowledge on hypoxia, physical agents, and chemical influences on cell health.
