Cell Injury Mechanisms Flashcards
Cell Injury
- Basic cell functions or viability are threatened
- Injury usually occurs due to situations where the ability of the cell to respond or adapt are exceeded
- Injury can be reversible or irreversible
Injured Cells
- Changes in available nutrients
- including oxygen
- Direct cell damage
- microorganisms
- Toxins
- Physical forces
Cell Injury:
Causes:
Physical Agents
Trauma, temperature extremes
Cell injury:
Causes:
Chemical
Xenobiotics (toxins), endogenous and exogenouse substances
Cell Injury:
Causes:
Nutrients
Too many or Too few
Cell injury:
Causes:
Infectious agents
Virus, bacteria
Cell Injury:
Susceptibility
- Cells have widely variable resistance to detrimental stimuli
- neurons and cardiac myocytes are highly susceptible to hypoxia
- Fibroblasts or squamous epithelium can survive in the absence of adequate oxygen
- Metabolic status will influence cell susceptibility
Cell Injury:
Mechanisms:
Loss of membrane integrity
Cell membrane breakdown and loose the ability to segregate reactions within the cell
- Free radical-induced damage
- Phospholipase-induced damage
- Direct membrane Damage
Cell injury:
Mechanisms:
Loss of ability to produce energy
ATP is insufficient to support cell functions
Cell injury:
Mechanisms:
Genetic Damage
Functional changes induced by a mutation
Free Radical Injury
- Free radicals are chemicals with unpaired electrons that readily react with surrounding molecules
- Chain reaction occurs as the electron passes from molecules to molecule
- Can damage membranes, as well as other cell components
- Formed during metabolism and by normal cell reactions
- Oxidation reduction reactions during areobic respiration
- Biotransformation of chemical substances
- Nitric oxide metabolism
Reactive Oxygen Metabolites:
Effects
- Protein and membrane degradation
- DNA damage
- Inflammation
Reactive Oxygen metabolites:
Implicated in
Aging
Neurodegeneration
Neoplasia
Cell injury and death
Chronic inflammation
Free Radical Injury:
Protective Mechanisms
- Vitamins A, C, and E phytochemicals (Antioxidants)
- Iron and copper binding proteins
- ferritin and ceruloplasmin
- Specific enzymes
- superoxide dismutase, Catalase, gluthathione peroxidase
Phospholipase-induced injury
- Activated membrane phospholipases cleave phospholipids out of the membrane
- Can be activated by increased cytoplasmic Ca++
- Phospholipase activation can also be cause by decreased energy
- Decreased energy interferes with membrane pump function and increased cytoplasmic Ca++
Direct Membrane Injury
- Certain substances can cause direct injury to membranes
- Bacterial Toxins
- xenobiotics
- Complements
Mechanisms:
Loss of ability to produce Energy
- Cell Injury = ATP
- ATP produced by
- oxidative phophorylation
- Anaerobic glycolysis
Role of Calcium in Cell injury
Mitochondrial injury
Phospholipase activation
Protease activation
Endonuclease activation
Mechanisms:
Genetic Injury
Damage to cellular nucleic acids is common
Permanent damage to DNA is a mutation
Mechanisms:
Genetic Injury
Outcomes
- No effect on the cell or tissues
- Cell dysfunction leading to disease
- Cell Transformation leading to neoplasia
- Cell death
Altered and Injured Cells:
Characteristics
- Cell injury can be either sublethal or lethal
- Sublethal injury can be reversible or progress to cell death
Altered and Injured Cells:
Characteristics:
Sublethal
Cell swelling
Intracellular accumulations
Neoplastic transformation
Altered and Injured Cells:
Characteristics:
Lethal
Apoptosis
Necrosis
Sublethal Injury:
Cell swelling
- Membrane ion pumps fail to maintain osmotic gradients across the membrane
- Water enters the cell or an intracellular organelle
- Morphology:
- Affected cells or organelles are swollen, and finely vacuolated
- “Hydropic changes”
Sublethal Injury:
Intracellular Accumulations
- Abnormal metabolism, functional demands that exceed the capability of hte cell, or exposure to injurious agents can lead to accumulation of various intracellular substances
- edogenous
- Exogenous
Endogenous Intracellular Accumulations
- Excess normal or abnormal metabolic products that accumulate in a cell
- Causes:
- Abnormal metabolism
- demand exceeds capability of the cell
- Cell injury that inhibits cell functions
- Examples:
- Metabolic storage disease
- Lipidosis
- Glycogenosis
- Intracellular Pigments
Endogenous Accumulations:
Lipidosis
- Metabolic pathways in cells are inhibited by injury or overwhelmed by excess demand
- Triglyceride accumulation is one common manifestation of metabolic change
- It can be physiological as well as pathological
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Endogenous Accumulations:
Lipidosis:
Physiologic causes
High fat ration
Increased periparturient engergy need
Anorexia
Endogenous Accumulations:
Lipidosis:
Pathologic Causes
Hyptotoxins
Hypoxia
Starvation
Endogenous Accumulations:
Glycogenosis
- Glycogen accumulates due to abnormal metabolism
- Hypatocytes of animals with diabetes mellitus
- Cells look “swollen”
Endogenous Accumulations:
Hemosiderin
- Intracellular Aggregates of Ferritin
- Commonly Associated with:
- Increased RBC sensecences
- Hemolysis
Endogenous Accumulations:
Lipofuscin-ceroid
Undegradable remnants of oxidized membrane lipid
It can accumulate as a part of aging or due to excessive membrane oxidation
Exogenous Intracellular Accumulations
The substances that accumulate are not native to the cell environment
These Include:
Viral Proteins and Nucleic Acids
Carbon
Non-Nutritive minerals
Sublethal Injury:
Transformation
- As a result of genetic injury soem cells undergo neoplastic transformation
- Transformed cells may have abnormal growth, often abnormal function, and abnormal morphology
- They are not injured, in the traditional sense, they are detrimentally changed
Sublethal Injury:
Transformation:
Morphology
- Cells may appear normal
- some degree of hyperplasia may be present
- Some cells appear poorly differentiated
- Anaplasia
- Some cells have vairable sizes/shapes/appearance
- Pleomorphism
Lethal Cell Injury
- The insult to the cell exceeds the cells ability to adapt or respond
- Lethal injury is immediate
- Sublethal injury can progress to lethal injury
- The severity of the insult may determine the outcome for the cell
- Many of the causes of lethal injury are the same as those for sublethal injury
- The severity of the insult may determine the outcome for the cell
Lethal Cell Injury:
Apoptosis
- Physiological Cell Death
- the mechanism to remove damaged or unneeded cells in the least disruptive way possible
- Apoptosis maintains homeostasis, but can also be involved in pathological states
- Apoptosis is an active process that requires energy from the cell
Apoptosis:
Causes:
Physiological
- Patterned death during embrygenesis
- Hormone/cytokine induced death
- tissue involution
- Maintain balance in proliferating populations
- Removal of cells following completion of their purpose
- Removal of self-reactive lymphocytes
Apoptosis:
Causes:
Pathologic
Unrepaired DNA damage
Heat
Hypoxia
Viral infections
Physical pressure
Lethal Cell injury:
Necrosis
- Death due to injury that disrupts the ability of the cell to continue to function
- Degradative process that occurs after the cell is dead
- Passive process, that does NOT require energy from the cell
Autolysis
self-digestion of a cell or tissue
Necrosis
Autolysis of a cell/tissue in a living animal
Postmortem Autolysis
Self-digestion of cells/tissues/organs after an animal dies
Necrosis:
Causes
- Direct Injury to the cell
- Hypoxia
- Direct Membrane Injury
- Many of the same facotrs that initiate apoptosis when the stimulus is mild, initiate necrosis when more severe
Necrosis:
Mechanisms
- Degradative Activity fo lytic enzymes
- Lysosomal enzymes degreade cell components
- Enzymes may come from the same cell
- Enzymes may come from other cells
Necrosis:
Morphology
- Eosinophilia
- protein denaturation
- Smooth, Homogenous cytoplasm “ground glass”
- Cytoplasmic vacuolation
- Nuclear degeneration
- Inflammation in response to necrosis
Post Mortem Autolysis
- Cells and tissues degradation that occurs following the death of an animal
- Changes that occur in cells are similar to those associated with antemortem necrosis
- Occurs ina predictable fashion
- All cells are affected and are at the same stage of autolysis
- There is no inflammation of host response
