1_cell injury, death, and adaptation

Reactive oxygen species.

An infarct.

Overview of Cellular Responses to Stress and Noxious Stimuli

Decreased protein synthesis, increased protein degradation in cells, and increased autophagy.

Profound disturbances in membrane function

Tissues with high (e.g., skin and GI tract) or low (e.g., heart and brain) cell turnover.

Normal, adapted, reversibly injured, and dead.

Focal areas of fat destruction.

A progressive decline in cellular function and viability caused by genetic abnormalities and the accumulation of cellular and molecular damage.

Lysosomal digestion of the cell’s own components, a survival mechanism initiated by proteins that sense nutrient deprivation.

In areas of necrosis, atherosclerotic arteries, damaged heart valves, and necrotic tumors.

Hypertrophy, hyperplasia, atrophy, and metaplasia.

Carbon tetrachloride (CCl4) and acetaminophen.

Immune reactions involving blood vessels.

They can recover if the stressor is removed.

It usually occurs in a single cell, hence it rarely triggers an inflammatory response.

Direct-acting toxins and latent toxins.

The binding of free fatty acids to calcium.

Collagenous fibrous tissue and the wall of arterioles in hypertension and diabetes mellitus.

Dilation of the ER with detachment of polysomes.

Reversible changes in the number, size, phenotype, metabolic activity, or functions of cells in response to changes in their environment.

Cell shrinkage, chromatin condensation, and karyorrhexis.

The type of injury, its duration, and severity.

In interstitial tissues of the gastric mucosa, kidneys, lungs, systemic arteries, and pulmonary veins.

Nephrocalcinosis is the deposition of calcium salts in the kidneys due to metastatic calcification.

Renal atrophy, renal infarction, and acute renal failure.

Hypertrophy (compensatory increase in cell size).

Ag-Ab complex deposition.

Hypertrophy.

Necrotic cell death.

An increase in the number of cells.

Ubiquitin-proteasome pathway.

Exposure to exogenous influences.

A change in the type of cells.

Necroptosis occurs in both physiologic and pathologic conditions.

It causes water to accumulate in the cell, leading to swelling.

Increased parathyroid hormone, destruction of bone tissue, vitamin D-related disorders, and renal failure.

By enzymes that neutralize them.

Chaperones.

Endometrial hyperplasia due to excessive hormonal or growth factor stimulation.

Squamous metaplasia.

In cells and tissues with a strong ability to divide.

Excessive use of estrogen.

Xanthomas are cholesterol deposits that occur in the subepithelial connective tissue of the skin.

Through chromosome or gene defects.

They appear as yellow nodules, often around the eyes.

Necrosis is the death of tissue following irreversible injury.

Mechanical stretch, agonists, and growth factors.

Atrophy caused by decreased workload, such as immobilization of a limb.

Fibrinoid necrosis.

Apoptosis.

An increase in the size of cells.

A condition caused by the accumulation of carbon (coal dust) in the lungs.

Protein accumulation.

Phagophore  Autophagosome  fuses with lysosomes  autophagolysosome.

A type of pathologic calcification that occurs in abnormal tissue deposition of calcium salts.

Focal bacterial or sometimes fungal infections.

Clumping of chromatin.

The abnormal tissue deposition of calcium salts.

The stage of cell injury at which the deranged function and morphology of the injured cells can return to normal if the damaging stimulus is removed.

Steatosis (Fatty change) and Cholesterol and cholesterol esters.

They are phagocytosed.

Fatty change refers to the accumulation of lipid droplets within cells, which is a type of reversible cell injury.

The fragmentation of the nucleus.

Air pollutants, poisons, insecticides, carbon monoxide (CO), etc.

The fading of basophilia of chromatin.

Cholesterolosis is the accumulation of cholesterol in the lamina propria of the gallbladder.

They can persist for some time or be digested.

It is a condition where the restoration of blood flow to ischemic but viable tissues results in increased cell injury.

The expanding field of extracellular vesicles and their release in regulated cell death programs.

Yes, apoptosis can be either physiologic or pathologic.

1. Mitochondrial membrane, 2. Plasma membrane, 3. Lysosomal membrane

Release of activated pancreatic lipases due to acute pancreatitis.

Abnormal tissue deposition of calcium salts.

The accumulation of reactive oxygen species (ROS).

Anti-neoplastic chemotherapeutic agents and toxins made by microorganisms.

Diabetes.

Wear-and-tear or aging pigment.

Excessive intake or defective transport or catabolism.

Through processes such as aerobic respiration.

Tissue damage and various changes and their severity.

Hemosiderin is an iron-storage complex that commonly accumulates in areas of hemorrhage.

Lipids, Proteins, Hyaline change, Glycogen, Pigments (Exogenous and Endogenous).

Cell swelling.

Telomerase adds repetitive nucleotide sequences to the ends of telomeres, helping to maintain their length and delay replicative senescence.

Cells enter replicative senescence and stop dividing.

The disease reaches its peak with severe symptoms.

纤维素样坏死是免疫反应引起的坏死，常见于血管炎和自身免疫性疾病。

A glimpse of necroptosis and its relation to diseases.

Ferroptosis.

They accumulate sphingomyelin in macrophages.

Coagulative necrosis.

For days or weeks.

Necrosis.

They cannot recover and are permanently damaged.

Inhalation of excessive carbon can lead to its accumulation in the lungs, causing conditions like anthracosis.

Extremely unstable molecules that readily react with inorganic and organic compounds.

Cancer, neurodegenerative disorders, infectious disease, inflammatory bowel disease.

It can stress compensatory pathways in the ER and lead to cell death by apoptosis.

It appears as brown atrophy.

A reversible change where one differentiated cell type is replaced by another cell type.

Accumulating cellular damage, reduced capacity to divide, and reduced ability to repair damaged DNA.

Cellular swelling (hydropic change or vacuolar degeneration) and fatty change (accumulation of lipid droplets).

Reprogramming of stem cells that exist in normal tissue, or of undifferentiated mesenchymal cells present in connective tissue.

Exposure to a pathogen or harmful agent.

Columnar metaplasia.

Prodromal stage where early symptoms appear.

脂肪坏死是脂肪组织的坏死，常见于急性胰腺炎。

Fragmentation of the pyknotic nucleus.

Foam cells are macrophages that have ingested large amounts of cholesterol.

Nondividing cells such as heart and skeletal muscle cells.

In necrosis, the cell size is enlarged (swelling), whereas in apoptosis, the cell size is reduced (shrinkage).

Apoptosis is individual cell death that may be physiological or pathological, characterized by enzymatic degradation of proteins and DNA, initiated by caspases, and the recognition and removal of dead cells by phagocytes.

Cellular contents undergo enzymatic digestion in necrosis.

Reversible cell injury is a type of cellular damage that can be repaired if the stressor is removed, allowing the cell to return to its normal state.

A pathway of cell death in which cells activate enzymes that degrade the cells’ own nuclear DNA and nuclear and cytoplasmic proteins.

An alteration within cells or in the extracellular space that gives a homogeneous, glassy, pink appearance.

Genetic abnormalities and the accumulation of cellular and molecular damage due to exposure to exogenous influences.

A decrease in the size of cells.

No, necroptosis is caspase-independent but dependent on signaling by the RIPK1 and RIPK3 complex.

No, it refers to a morphological description, not a specific substance.

A round collection of calcium commonly seen in certain types of tumors.

Electron microscopy, optical microscopy of pathological sections, and observing cell function and tissue damage with the naked eye.

An endogenous pigment found in the skin.

It can lead to loss of enzyme activity and other cellular dysfunctions.

In foci of tuberculous infection.

Ferritin is an iron-storage protein that accumulates in areas of red blood cell hemorrhage.

凝固性坏死是细胞蛋白质变性和凝固的结果，常见于心脏、肾脏和脾脏。

Intracellular accumulation.

They are accumulations of excessive amounts of normal secretory protein.

Apoptosis, necrosis, and autophagy.

Aggregation of abnormally folded proteins.

They are morphologically distinct and depend on the underlying cause.

Uterus during pregnancy and bodybuilders.

The increase in cell size is due to the increased synthesis of proteins.

Decreased workload (disuse atrophy), loss of innervation (denervation atrophy), diminished blood supply (ischemia), inadequate nutrition, loss of endocrine stimulation, and pressure.

The brain.

Loss of endocrine stimulation can lead to atrophy as hormones are necessary for the maintenance of certain tissues.

Mild inflammation and severe inflammation

Mitochondrial dysfunction.

The regulation stage.

Carbon (coal dust), anthracosis, tattooing.

Cytochrome C is released.

Reduced metabolic activity.

Blebbing, blunting, and distortion of microvilli.

The cell membrane remains intact.

1. Inability to reverse mitochondrial dysfunction 2. Profound disturbances in membrane function

Enzyme digestion.

Tattooing introduces exogenous pigments into the skin.

Oxygen-derived free radicals.

Hypoxia is a deficiency in the amount of oxygen reaching tissues, while ischemia is an inadequate blood supply to an organ or part of the body.

A condition where the production of ROS exceeds the cell's ability to remove them.

An increase in the production of misfolded proteins or a reduction in the ability to eliminate them.

Dry gangrene appears as black, shriveled tissue and is less associated with bacterial infection compared to wet gangrene.

The cellular and tissue architecture disappears.

By creating a deficiency of an essential protein or by inducing apoptosis.

A special form of coagulative necrosis with limited liquefaction.

Conditions like abscesses or acne (pustules).

Malignant transformation in metaplastic epithelium.

Hemosiderosis.

Steatosis is the accumulation of fat within cells, also known as fatty change.

Denaturation of cellular proteins, leakage of cellular contents through damaged membranes, local inflammation, and enzymatic digestion of the lethally injured cell.

Exogenous and Endogenous pigments.

High turnover (e.g., skin and GI tract) and low turnover (e.g., heart and brain).

Fat degrades to glycerol and free fatty acids.

Necroptosis is triggered by the ligation of TNFR1 and viral proteins of RNA and DNA viruses.

Swelling and the appearance of phospholipid-rich amorphous densities.

Inability to reverse mitochondrial dysfunction

Metastatic calcification is the deposition of calcium salts in normal tissues due to hypercalcemia.

Myelin figures are collections of phospholipids derived from damaged cellular membranes.

An increase in the number of cells in an organ or tissue in response to a stimulus.

Cytoplasmic buds and membrane-bound apoptotic bodies.

Cellular swelling, also known as hydropic change or vacuolar degeneration, is a type of reversible cell injury.

Growth factor-driven proliferation of mature cells and increased output of new cells from tissue stem cells.

The brush border initially remains clear but may disappear as the injury progresses.

Loss of RNA.

Heart, skeletal muscle, kidney.

Alcoholic hyaline (keratin) and neurofibrillary tangles in Alzheimer disease (neurofilament).

Triglycerides, cholesterol/cholesterol esters, and phospholipids.

Myocardial hypertrophy and chronic hemodynamic overload resulting from either hypertension or a faulty valve.

Physiologic atrophy is the shrinkage of cells due to aging, such as in the breast and uterus.

Hypoxia and ischemia leading to ATP depletion, ischemia-reperfusion injury, oxidative stress, protein misfolding, DNA damage, mitochondrial dysfunction, and membrane damage.

Pathologic calcification is the abnormal deposition of calcium salts in tissues, which can be dystrophic (occurring in dead or dying tissues) or metastatic (occurring in normal tissues due to hypercalcemia).

粒線體會損壞，細胞膜和細胞器膜（包括粒線體膜）會破裂和滲漏，粒線體會腫脹、斷裂，最終導致細胞內容物的釋放。

粒線體是細胞能量代謝的關鍵，其功能的改變可誘導細胞凋亡，並由 Bcl-2 家族蛋白調控粒線體膜的完整性和對凋亡信號的反應。

Necroptosis is a form of programmed cell death that resembles necrosis morphologically and apoptosis mechanistically.

The cell membrane structure is maintained during cell death.

It is not a distinctive pattern but rather ischemic coagulative necrosis, frequently of a limb, especially common in diabetes.

Atrophy that occurs due to aging.

Reversible changes in the size, number, phenotype, or functions of cells in response to changes in their environment.

Wet gangrene is gangrenous necrosis with a bacterial infection, considered a severe form of coagulative necrosis.

Poor nutritional status or degenerative changes leading to mineral deposition.

Fragmentation of DNA.

The type of cell, its metabolic state, adaptability, and genetic makeup.

Cell injury.

Telomeres protect the ends of chromosomes and shorten with each cell division, eventually leading to replicative senescence when they become too short.

Ischemia.

液化性坏死是组织被消化酶液化，常见于脑组织和脓肿。

Infectious agents.

Convalescence or recovery period where symptoms decline and health is restored.

湿性坏疽是由于细菌感染引起的坏死，常见于四肢和肠道。

Cell injury, which can be reversible or irreversible.

Coagulative, liquefactive, gangrenous, caseous, fat, and fibrinoid.

Increased protein synthesis.

The two main types of cell death are apoptosis and necrosis.

Decreased hormone levels lead to reduced survival signals, causing apoptosis.

外部因素如創傷、毒素或缺氧。

Hypoxic death in the brain (brain infarct).

It leads to cell swelling and loss of microvilli structure.

Columnar to squamous (Squamous metaplasia).

Hormonal hyperplasia (e.g., breast at puberty and pregnancy) and compensatory hyperplasia (e.g., liver after partial resection).

Cheesy, white, structureless, amorphous granular debris.

A granuloma is an area of caseous necrosis enclosed within a distinctive inflammatory border.

Incubation period where the pathogen begins to multiply.

Liver.

Protein accumulation.

The EMBO Journal.

An increase in the size of a cell.

Increased generation of reactive oxygen species (ROS).

Increased generation of ROS during reoxygenation and increased inflammation.

The nucleus fragments during apoptosis.

Ischemia caused by obstruction in the vessel.

Persistent pressure on tissues can cause them to shrink, as seen in conditions affecting the kidney.

Apoptosis is a mechanism of programmed cell death.

中和細胞質中的 caspase 抑制劑。

Leakage of intracellular proteins.

Protein accumulation.

Increased telomerase activity can extend the lifespan of a cell by maintaining telomere length and delaying senescence.

Toxins, protein malnutrition, diabetes mellitus, obesity, anoxia, alcoholic abuse, and nonalcoholic fatty liver disease.

Protein-calorie insufficiency and vitamin deficiency.

Inflammation induced by ischemic injury may increase, leading to an influx of leukocytes and plasma proteins, and activation of the complement system.

The nucleus undergoes pyknosis, karyorrhexis, and karyolysis in necrosis.

Caspases.

Atrophy caused by diminished blood supply.

The main topics include reversible cell injury, cell death, mechanisms of cell injury, cellular adaptations to stress, intracellular accumulations, pathologic calcification, and cellular aging.

Cellular adaptations to stress are changes that cells undergo in response to chronic stress, including hypertrophy, hyperplasia, atrophy, and metaplasia.

DNA damage, accumulation of misfolded proteins, and infections, especially certain viral infections.

It completely obliterates tissue architecture, making it cheese-like.

In the intimal layer of the aorta and large arteries.

Hypersensitivity and autoimmune diseases.

Abnormal accumulation of triglycerides within parenchymal cells.

干性坏疽是由于缺血引起的坏死，常见于四肢。

Targeting regulated non-apoptotic cell death.

Shrinkage in the size of a cell by the loss of cell substance.

Activation of the complement system can increase inflammation and cell injury.

Atrophy caused by loss of innervation.

Necrosis is typically pathologic.

During embryogenesis, turnover of proliferative tissues, involution of hormone-dependent tissues, decline of leukocyte numbers at the end of immune and inflammatory responses, and elimination of potentially harmful self-reactive lymphocytes.

粒線體膜的通透性增加，釋放出細胞色素 c 等蛋白質，並與 Apaf-1 和前體 caspase-9 結合形成凋亡體，啟動 caspase 級聯反應。

Viral proteins activate the mitochondrial pathway, and cytotoxic T lymphocytes kill infected cells by activating caspases.

干酪性坏死是一种特殊类型的坏死，组织呈现奶酪样外观，常见于结核病。

Nuclear shrinkage and increased basophilia.

A lysosomal storage disease characterized by the accumulation of cholesterol in multiple organs.

Trauma, extreme temperatures, radiation, etc.

A mutation in the enzyme responsible for transporting cholesterol.

It accumulates cholesterol.

Denaturation.

Yes, cellular contents remain intact in apoptosis.

Their influx contributes to the inflammation that exacerbates cell injury.

In necrosis, the plasma membrane is disrupted, while in apoptosis, it remains intact.

Inflammation is frequent in necrosis but not in apoptosis.

Common mechanisms of cell injury include hypoxia, chemical agents, infectious agents, immunologic reactions, genetic factors, nutritional imbalances, and physical agents.

細胞色素 c 和 SMAC 等蛋白質。

調控粒線體膜的完整性和對凋亡信號的反應。

Inadequate nutrition can cause cells to shrink due to lack of necessary nutrients.

Cellular aging refers to the progressive decline in cellular function and viability caused by genetic and environmental factors, leading to the aging of the organism.

They activate proapoptotic proteins in response to DNA damage and accumulation of misfolded proteins.

Intracellular accumulations are the build-up of substances that cells cannot immediately use or eliminate, which can be normal cellular constituents, abnormal substances, or pigments.

They decline due to loss of survival signals as the stimulus for leukocyte activation is eliminated.

DNA damage activates proapoptotic proteins by BH3-only sensors.

Loss of growth factor signaling leads to apoptosis during embryogenesis and turnover of proliferative tissues.

Strong recognition of self-antigens induces apoptosis by both the mitochondrial and death receptor pathways.

necrosis 導致粒線體的整體損壞，而 apoptosis 則引起粒線體釋放特定蛋白質，但粒線體本身並不會完全破壞。

細胞損傷是指細胞在面對壓力或有害刺激時，無法維持正常功能的狀態。

細胞死亡的兩種主要形式是壞死和凋亡。