Mechanism of cell injury Flashcards
1
Q
What is Cell Injury?
A
- When basic cell functions or viability are threatened
- Usually occurs due to situations where the ability of teh cell to respond or adapt are exceeded
- Can be reversible or irreversible
2
Q
What are general causes of cell injury?
A
- Changes in available nutrients
- Direct cell damage
- microorganisms
- Toxins
- Physial forces
3
Q
What are the specific causes of Cell injury?
A
- Physical agents:
- Trauma, temperature extremes
- Chemicals:
- Xenobiotics (toxins, endogenous and exogenous substances
- Nutrients:
- Too few, too many
- Infectious agents
4
Q
What determines a cells susceptibility to injury?
A
- 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
5
Q
What are the mechanisms for cell injury?
A
- Loss of membrane integrity
- Loss of ability to produce energy
- Genetic damage
6
Q
How does the loss of membrane integrity cause cell injury?
A
- Cell membranes breakdown and lose the ability to segregate reactions within the cell
- Damage to the plasma membrane removes the barrier to the extracellular environment and the gradients that it forms
- Damage to organelle membranes disrupts the segregation of reactions within a cell
7
Q
What are the mechanisms that cause loss of membrane integrity?
A
- Free radical-induced damage
- Phopholipase-induced damge
- Direct membrane damage
8
Q
What is Free Radical Injury?
A
- Free radicals are chemicals with unparied electron that readily react with surrounding molecules
- A chain reaction occurs as teh electon passes from molecule to molecule
- Free radicals can dmage membranes, and other cell components
- Free radicals are formed during metaboism and by normal ell reactions
9
Q
How are Free Radicals created?
A
- Formed during metabolism and by normal cell reactions
- Oxidation reduction reaction during aerobc respiration
- Oxygen-derived products are the most important types o free radicals i tissues and cells
- Biotrnssfomation ocf chemical substances
- Transient, highly reactive intermediate compounds are formed
- Nitric oxide metabolism
- Oxidation reduction reaction during aerobc respiration
10
Q
What are the effects of Reactive Oxygen Metabolites?
A
- Protein and membrane degradation
- DNA damage
- Inflammation
- Implicated in:
- Aging
- Neurodegeneration
- Neoplasia
- Cell injury and death
- Chronic inflammation
11
Q
What are the protective mechanisms against Free Radical Injury?
A
- Vitamins A, C, and E (antioxidants): phytochemicals
- Iron ad coppor binding proteins
- Ferritin
- ceruloplasmin
- others
- Specific enzymes:
- Superoxide dismutase
- Catalase
- Glutathione peroxidae
- Others
12
Q
What is Phospholipase-Induced Injury?
A
- Activted membrane phospholipases cleave phospholipids out of the membrane
- These can be activated by increased cytoplasmic Ca+2 among other activators
- Phospholipase activation can also be caused by decreased energy
- Decreased energy results in interference with membrane pump function and increased cytoplasmic Ca+2
13
Q
What is Direct Membrane Injury
A
- Certain substances can cause direct injury to membranes
- Bacterial toxins
- Xenobiotics
- Complement system
14
Q
How does the loss of the ability to produce energy cause cell injury?
A
- ATP is insufficient to support cell functions
- ATP is produced in 2 pathways
- Oxidative phosphorylation - Mitochondria, highly efficient
- Anaerobic glycolysis - Cytoplasm, poorly efficient
- Failure of energy-dependent membrane pumps (NA+/K+ and Ca+2/Mg+2
- Decreased intracellular pH
- Decreased protein syntehesis
- Cytoskeletal degradation
- Ca+2 induced coagulation
- Membrane degradation
- Leakage of organelle contents
- Organelle dysfunction
15
Q
What role does Calcium play in Cell injury?
A
- Mitochondrial injury
- Phospholipase activation
- Protease activation
- Endonuclease activation
16
Q
What is Genetic Injury?
A
- Damag to cellular nucleic acids is common
- most damage is repaired and transient
- Permanent damage to DNA is a mutation
17
Q
What are the outcomes of genetic injury?
A
- No effect on cell or tissue
- Cell dysfunction leading to disease
- developmental anomalies, storage diseses
- Cell transformation leading to neoplasia
- Cell death - apoptosis
19
Q
What is Cell Swelling?
A
- Membraneion pumps fail to maintain osmotic gradients across the membrane
- water enters the cell or an intracellular organelle along an osmotic gradient
- Morphology
- Affected cells or organelles are swllen and finely vacuolated
- Hydropic change
23
Q
What is Lipidosis
A
- 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
- Most apparent in those cells which metabolize large amounts of fat
- When due to cell injury, often occurs concurrently with cell swelling
- Morphology:
- Cytoplasmic vacuoles of variable size
26
Q
What is Glycogenosis?
A
- Glycogen accumulates due to abnormal metabolism
- Hepatocytes of animals with diabetes mellitus
- Cells look “swollen”
27
Q
What is hemosiderin?
A
- Intracellular aggregates of ferritin (iron protein conjugate)
- Commonly associated with:
- increased RBC senescence
- Hemolysis
28
Q
What is Lipfuscin-ceroid accumulation?
A
- Endogenous
- Undegradable remnants of oxidized membrane lipids
- It can accumulate as a part of aging or due to excessive membrane oxidatoin
29
Q
What are Exogenous Intracellular accumulations
A
- Substances that accumulate are not native to the cell environment
- Include:
- Viral proteins and nucleic acids (“inclusions”)
- Carbon
- Non-nutritive minerals (eg. lead)
41
Q
What is the morphology of necross?
A
- Eosinophilia - protein denaturation
- Smooth, homogenous (“ground glass”) cytoplasm
- Deterioration of organelles
- Cytoplasmi vacuolation
- Nuclear degeneration
- Karyolysis, Karyorrhexis, pyknosis
- Inflammation in response to necrosis
