Week 1: Cell Injury Flashcards
A cell’s response to stress depends on the ________________________ and the _______________.
dose intensity of stressor ; cell’s vulnerability
3 basic cellular responses to stress
1) Injury: reduced function / may not be reversible
2) Adaption: Cell takes different forms
3) Death: cessation of cellular activity
What are the criteria for irreversible cell injury?
When ATP drops below certain level or when membranes are damaged beyond repair
Energy-dependent functions of a cell fail due to what?
ATP depletion which results from hypoxia or anoxia
What does mitochondrial damage usually result from?
Genetic disorders
Toxins
Medications
If a cell is subject to lots of ROS, toxins or trauma, what might that cause?
An increase in permeability of the cell membrane
What does an accumulation of DNA or misfolded proteins result from?
Ionizing radiation
Reactive oxidative stress (ROS)
7 common causes of cell injury
Toxins Infections Genetic and metabolic diseases Trauma Reactive oxidative stress (ROS) Inflammatory responses Hypoxia and Anoxia
What is the initial response of a cell when they are low on oxygen? What happens to the cell? Why is this a problem?
Initial response is to switch to anaerobic respiration but this produces less ATP for the cell which can cause problems over long periods of time.
The cell begins to swell since the sodium potassium pumps are not able to use ATP. More sodium goes into cell which is followed by water. This causes swelling.
Also, failure of sodium calcium exchange.
Most common cell injury
Hypoxic injury
Reduction in oxygen
Hypoxia
Absence of oxygen
Anoxia
Loss of oxygen due to insufficient blood flow
Ischemic hypoxia/ anoxia
Most common form of hypoxia
Ischemic hypoxia
Iron-deficiency anemia, carbon monoxide poisoning
Anemic hypoxia
What do radical forms of ROS have?
They have an unpaired electron which makes them very reactive. They are partially REDUCED forms of oxygen and are energetically unstable.
Describe Reactive Oxidative Species (ROS). Give 4 examples. Their forms. What neutralizes them?
Produced in mitochondria during ATP production, produced by immune cells. Examples include hydrogen peroxide, superoxide, nitric oxide, ozone. Can be in radical or non-radical forms. They break covalent bonds between molecules and can cause damage. Neutralized by anti-inflammatories.
3 associated injuries due to reactive oxygen species (ROS)
Lipid per oxidation
Protein Degradation
DNA damage
3 oxygen-derived free radicals
1) O2 - superoxide
2) H202 - hydrogen peroxide
3) OH - Hydroxyl
Anti-oxidants that neutralize ROS
Superoxide dismutase
Peroxidases
Catalase
Antioxidants
2 Occular effects of unchecked ROS
Cataracts
ARMD
3 examples and effects of direct toxicity
Lead - CNS toxicity
Mercury - CNS toxicity
Carbon Monoxide - Anemic hypoxia
3 examples and effects of indirect toxicity
Ethanol - CNS and liver toxicity
Ethanbutol - Toxic Optic Neuropathy
Cyclosporine - Retinal toxicity. Immunosupressant and Restasis
What type of injury is an infection?
Direct or indirect damage
What is Ethambutol used for? What are its effects on the eyes?
- Used to treat TB and MAC
- Causes vision loss as side effect
- painless progressive LOV, decreased VA
- central/centrocecal scotoma
- optic nerve becomes pale over time
- no safe dosage, greater than 15 mg is toxic
- can start to lose vision as soon as 2 weeks
True or false:
Normal immune responses can someetimes cause damage to the surrounding healthy tissues.
True
Things produced in immune response and inflammatory response that can be damaging
Phagocytic cells Antibodies Complement Enzymes Free Radicals
Describe genetic and metabolic injury
Flawed genetic codes cause disruptions in normal cellular behavior which typically lead to cell injury and death
4 examples of metabolic and genetic injuries
Sickle Cell anemia
Fatty liver disease
Hepatolenticular Disease
Type 2 diabetes
Explain Hepatolenticular Disease. What kind of injury is it? What is its relevance to the eyes?
- Genetic/metabolic injury
- Body can’t remove excess iron.
- Defect in ATP7B protein. Creates free radicals which create holes in membrane. Iron goes through membrane and transported to other tissues.
- Iron can be transported to the Descemet’s membrane of the cornea and can be seen as rings near the limbus called Kayser Fleisher rings.
4 types of traumatic injuries
Blunt force trauma
Sharp force trauma
Penetrating trauma
Ionizing radiation
Cells shrink and reduce their differentiated functions
Atrophy
Increased cell size
Hypertrophy
Increased cell number
Hyperplasia
Potentially transform into cancerous tissue
dysplasia
Conversion of one cell type to another
Metaplasia
Two primary theories of aging
1) Accumulation of injurious events
2) Genetically controlled programs
Initiated by cell injury, leads to inflammation
Necrosis
The more specialized a cell, the more ____________ it is to injury
vulnerable
Clumping of chromatin in nucleus
Pyknosis
Fragmentation of the nucleus
Karyorrhexis
Nuclear dissolution of chromatin lysis
Karyolysis
Pyknosis, karyolysis, and karyorrhexis in order
Pyknosis, karyorrhexis, then karyolysis
loss of electron
oxidation
gain electron
reduction
Describe reperfusion. Give examples
When there is schema hypoxia, reactive species are created without oxygen. Then, blood flow gets reintroduced and interacts with those molecules and can worsen injury.
Examples:
Transplant
myocardial infarction (heart attack)
stroke
What does carbon monoxide do?
Direct toxin.
Binds to hemoglobin and displaces oxygen
Immune cells produce ____ that attack ______________
ROS ; cellular membranes
cooling of the body during death
algor mortis
pooling of blood during death
livor mortis
muscle contraction during death
rigor mortis
