Cell Injury Mechanisms Flashcards
(47 cards)
1
Q
Cell Injury
A
- 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
2
Q
Injured Cells
A
- Changes in available nutrients
- including oxygen
- Direct cell damage
- microorganisms
- Toxins
- Physical forces
3
Q
Cell Injury:
Causes:
Physical Agents
A
Trauma, temperature extremes
4
Q
Cell injury:
Causes:
Chemical
A
Xenobiotics (toxins), endogenous and exogenouse substances
5
Q
Cell Injury:
Causes:
Nutrients
A
Too many or Too few
6
Q
Cell injury:
Causes:
Infectious agents
A
Virus, bacteria
7
Q
Cell Injury:
Susceptibility
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
8
Q
Cell Injury:
Mechanisms:
Loss of membrane integrity
A
Cell membrane breakdown and loose the ability to segregate reactions within the cell
- Free radical-induced damage
- Phospholipase-induced damage
- Direct membrane Damage
9
Q
Cell injury:
Mechanisms:
Loss of ability to produce energy
A
ATP is insufficient to support cell functions
10
Q
Cell injury:
Mechanisms:
Genetic Damage
A
Functional changes induced by a mutation
11
Q
Free Radical Injury
A
- 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
12
Q
Reactive Oxygen Metabolites:
Effects
A
- Protein and membrane degradation
- DNA damage
- Inflammation
13
Q
Reactive Oxygen metabolites:
Implicated in
A
Aging
Neurodegeneration
Neoplasia
Cell injury and death
Chronic inflammation
14
Q
Free Radical Injury:
Protective Mechanisms
A
- Vitamins A, C, and E phytochemicals (Antioxidants)
- Iron and copper binding proteins
- ferritin and ceruloplasmin
- Specific enzymes
- superoxide dismutase, Catalase, gluthathione peroxidase
15
Q
Phospholipase-induced injury
A
- 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++
16
Q
Direct Membrane Injury
A
- Certain substances can cause direct injury to membranes
- Bacterial Toxins
- xenobiotics
- Complements
17
Q
Mechanisms:
Loss of ability to produce Energy
A
- Cell Injury = ATP
- ATP produced by
- oxidative phophorylation
- Anaerobic glycolysis
18
Q
Role of Calcium in Cell injury
A
Mitochondrial injury
Phospholipase activation
Protease activation
Endonuclease activation
19
Q
Mechanisms:
Genetic Injury
A
Damage to cellular nucleic acids is common
Permanent damage to DNA is a mutation
20
Q
Mechanisms:
Genetic Injury
Outcomes
A
- No effect on the cell or tissues
- Cell dysfunction leading to disease
- Cell Transformation leading to neoplasia
- Cell death
21
Q
Altered and Injured Cells:
Characteristics
A
- Cell injury can be either sublethal or lethal
- Sublethal injury can be reversible or progress to cell death
22
Q
Altered and Injured Cells:
Characteristics:
Sublethal
A
Cell swelling
Intracellular accumulations
Neoplastic transformation
23
Q
Altered and Injured Cells:
Characteristics:
Lethal
A
Apoptosis
Necrosis
24
Q
Sublethal Injury:
Cell swelling
A
- 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”
25
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
26
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
27
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
*
28
Endogenous Accumulations:
Lipidosis:
Physiologic causes
High fat ration
Increased periparturient engergy need
Anorexia
29
Endogenous Accumulations:
Lipidosis:
Pathologic Causes
Hyptotoxins
Hypoxia
Starvation
30
Endogenous Accumulations:
Glycogenosis
* Glycogen accumulates due to abnormal metabolism
* Hypatocytes of animals with diabetes mellitus
* Cells look “swollen”
31
Endogenous Accumulations:
Hemosiderin
* Intracellular Aggregates of Ferritin
* Commonly Associated with:
* Increased RBC sensecences
* Hemolysis
32
Endogenous Accumulations:
Lipofuscin-ceroid
Undegradable remnants of oxidized membrane lipid
It can accumulate as a part of aging or due to excessive membrane oxidation
33
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
34
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
35
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
36
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
37
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
38
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
39
Apoptosis:
Causes:
Pathologic
Unrepaired DNA damage
Heat
Hypoxia
Viral infections
Physical pressure
40
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
41
Autolysis
self-digestion of a cell or tissue
42
Necrosis
Autolysis of a cell/tissue in a living animal
43
Postmortem Autolysis
Self-digestion of cells/tissues/organs after an animal dies
44
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
45
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
46
Necrosis:
Morphology
* Eosinophilia
* protein denaturation
* Smooth, Homogenous cytoplasm “ground glass”
* Cytoplasmic vacuolation
* Nuclear degeneration
* Inflammation in response to necrosis
47
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
