Cellular Stress - Injury, Adaption, and Cell Death Flashcards
What occurs when the environmental changes exceed the capacity of the cell?
Cell injury
What are the different agents that can cause cell injury? (7)
- Hypoxia
- Physical agents ex. radiation, extreme temp
- Chemical agents ex. poison, drugs
- Biological/Infectious agents ex. microorganisms
- Immunologic reactions ex. allergens
- Genetic alterations
- Nutritional Imbalances
What are the four cell components that are particularly vulnerable?
- cell membranes critical for ionic and osmotic homeostasis
- mitochondria and the generation of energy via ATP
- protein synthetic machinery
- cellular DNA
What occurs when there is persistent sub lethal injury to the cell?
The cell adapts to the environment; the cell achieves a new steady state and preserves cells viability
What are some of the adaptive responses of cells to injury? (5)
- regulation of cell receptors
- changes in cell protein synthesis and turnover
- adaption to cell size (atrophy or hypertrophy)
- adaption to cell number (hyperplasia)
- adaption to phenotype and organization of cells (metaplasia, dysplasia)
What is Hypertrophy?
- Increase in the size of existing cells, due to the increase in synthesis of cellular protein and structural components and organelles responsible for producing them
- can be pathological or physiological in response to increasing functional demand or specific hormonal stimulation
What is Hyperplasia?
Increase in number of cells caused by cell division
What are some physiological examples of Hyperplasia and Hypertrophy?
- hyperplasia and hypertrophy of uterine smooth muscle occur in pregnancy in response to estrogen
- compensatory hyperplasia occurs when a portion of tissue is removed
- hypertrophy of skeletal muscle occurs as a normal physiological response in weight training
What are some pathological examples of Hyperplasia and Hypertrophy?
- hypertrophy of cardiac muscle fibers occurs in response to increased workload as a result of systemic hypertension
- excessive stimulation of the normal uterus by estrogen may result in endometrial hyperplasia
What is Metaplasia?
When certain types of cells, change into different types of cells due to the long-term environment that they are in becoming unsuitable for them
What is Dysplasia?
- an alteration in the size, shape and organization of the cellular components of a tissue
- may be reversible after the irritating cause has been removed
Where does Dysplasia often occur?
In metaplastic squamous epithelium of the respiratory tract and cervix
What is Atrophy?
- a decrease in mass due to the shrinkage in cell size
- due to diminished blood supply or diminished nutritional or trophic factors, a new steady state is reached in which a smaller cell is able to survive
What are some physiological and pathological examples of Atrophy?
- normal aging (ex. Shrinkage and loss of brain cells with age
- Disuse of skeletal muscle in an immobilized limb
- degeneration following loss of nerve input to the muscle
What is a Reversible injury?
When the injurious stimulus is mild and transient, and the cell is capable of recovery and return to normal state
What occurs when the injury stimulus is severe or progressive, and the cell undergoes irreversible damage?
Death of the cell
What are the 2 mechanisms by which cells die?
- Apoptosis
- Necrosis
What is Apoptosis?
The death of cells which occurs as a normal and controlled part of an organism’s growth and development
What is Necrosis?
The death of body tissue, which occurs when there is too little blood flow to the tissue
What is Cellular Proliferation?
The division and reproduction of cells
Including:
- replication of DNA
- synthesis of all cellular constituents for a new cell
- equal division of all these things between the original cell and new daughter cell during mitosis
What are the 4 phases of the cell cycle?
G1 - where cells grow in mass
S - where DNA is synthesized
G2 - where further growth occurs
M - the mitotic phase where the cell divides
What is the G0 phase?
additional phase of quiescent cells that are not actively cycling
- Stable cells such as Hepatocytes rest in the phase
How can cells enter the G1 phase?
- from the geno-quiescent cell pool
- after completing a round of mitosis if they are continuously replicating
- label cells such as stem cells of the skin or GI tract
What permanent cells exit the cell cycle permanently and do not replicate?
Neutrons and cardiac muscle cells
By what is the cell cycle regulated?
By activators and inhibitors
What are the activators that regulate the cell cycle?
cyclones and their associated enzyme, cyclin dependent kinases CDK’s
How is the cell cycle controlled?
By CDK inhibitors, which delay cell cycle progression at the G1 to S and G2 to M transition points to check for DNA damage
What occurs if damage is detected in the cell cycle?
DNA repair mechanisms are initiated
What occurs if the damage detected in the cell cycle is too severe?
The cell will either undergo death by apoptosis, or it may enter Senescence, a non-replication state
How may a Malignant Tumour develop?
If CDK inhibitors are defective, there is the potential for cells with damaged or mutated DNA to divide, forming the tumour
What is the Warburg Effect?
It involves increased cellular uptake of glucose and glutamine, increased glycolysis, and decreased oxidative phosphorylation. These changes become fixed cancer cells
What are Stem cells?
- cells that during development give rise to all differentiated tissues
- in adults, stem cells replace damaged cells and maintain tissue populations
What are the different types of Stem cells?
- Embryonic
- Tissue
What are Embryonic Stem cells?
- cells that are present in inner cell mass of blastocyst
- they have virtually limitless self-renewal capacity
- type: totipotent
What are Totipotent stem cells?
stem cells that can give rise to any type in the body
What are Tissue Stem Cells?
- cells that are found admired with differentiated cells in tissues
- Can only generate certain differentiated cells - usually only those that are normal constituents of that tissue
What is Ischemia?
a condition in which the blood flow (and thus oxygen) is restricted or reduced in a part of the body
What occurs during Ischemia? (4)
- cell injury
- coagulative necrosis
- disappearance of oxygen and substrates for glycolysis
- disappearance of continued ATP generation
What are the sequence of steps that as a result of reduced levels of O2 during ischemia results in Necrosis? (5)
- decreased O2 compromises respiration in mitochondria damaging the ability to produce ATP
- decreased ATP causes the accumulation of Na in the cell and the diffusion of K out of the cell
- accumulation of Na causes cells to swell, resulting in damage or rupture of the cell membranes
- More acidic environment due to increased anaerobic glycolysis and the depletion of glycogen resulting in buildup of lactic acid
- decreased ATP and pH levels cause ribosomes to detach from the rough endoplasmic reticulum (RER) with a reduction in protein synthesis
What occurs if Ischemia is not relieved? (4)
- worsening mitochondrial function
- increasing membrane permeability
- proteolytic enzymes are released due to the acidic environment, inducing widespread damage
- calcium increases in the cells, leading to many enzyme systems to activate inappropriately
What are blood serum samples used to measure in regards to cell injury and death?
they are used to measure the leakage of cell proteins across the degraded cell membrane into the peripheral circulation
What are the 4 major mechanisms of cell injury?
- Mitochondrial damage
- Entry of Ca2+
- Membrane damage -> plasma membrane, lysosomal membrane
- Protein misfolding, DNA damage -> activation of pro-apoptotic proteins
What can occur at early stages or in mild forms of injury?
The functional and morphological changes are entirely reversible if the stimulus is removed
What are the two types of cell death?
- Necrosis
- Apoptosis
What are the two types of Reversible Cell Injury?
- Hydropic Swelling
- Fatty Changes
What is Hydropic Swelling?
- Injury caused by a variety of agents producing a characteristic cellular or hydropic swelling when seen under the microscope
- an increase in cell volume characterized by a large, pale, and vacuolated cytoplasm and a normally located nucleus
What does Hydropic Swelling cause?
- Impairment of the process that controls ionic concentrations in the cytoplasm
- can impair the energy-dependent Na-K plasma membrane pump leading to an accumulation of Na in the cell
What does Hydropic Swelling lead to?
An increase in water in the cell to maintain isosmotic conditions and the cell swells
What is Fatty change?
a form of reversible adaptation to cell stressors, the abnormal accumulation of triglycerides within cells
How does Fatty change occur? (3)
- an increased delivery of fat to the cell
- an impairment of fat metabolism within the cell
- decreased synthesis of apolipoproteins for transport out of the cell
What occurs during Fatty change?
Small vacuoles of fat appear throughout the cytoplasm or may coalesce to form one large vacuole that displaces the nucleus as a result of:
- toxin exposure
- protein malnutrition or starvation
- diabetes
- obesity
- anoxia
Where does Fatty change occur? (4)
- liver
- heart
- kidney
- skeletal muscle
What are the characterizations of Necrosis?
- Eosinophilia (pinkness) of the cytoplasm
- Pyknosis (shrinkage) of the nucleus
- Karyorrhexis (pyknotic nucleus fragments or breaks up) the nucleus
- Karyolysis (dissolution) of the nucleus
What are the different types of Necrosis?
- Coagulative
- Liquefactive
- Fat
- Caseous
What is Coagulative Necrosis?
- most common form
- cells appear like “ghosts”
- typical of ischemia
- ex. in heart cells
What is Liquefactive Necrosis?
Rapid loss of tissue architecture and digestion of the dead cells
- most seen in CNS
- typical of bacterial infection or death of brain tissue
What is Fat Necrosis?
Released enzymes digest fat that complexes with calcium to form chalky-white deposits
- specific to fat (adipose) tissue
ex. pancreatitis, damage to breast tissue
What is Caseous Necrosis?
- Soft, friable, “cheesy” material
- characteristic of tuberculosis
What is Gangrenous necrosis?
coagulative necrosis when there is superimposed infection with a liquefactive component
- most frequently of a limb
What is Dry Gangrene?
If the necrotic tissue dries out (with no infectious component, and it becomes dark black and mummified
What is Apoptosis?
- morphological manifestation of programmed cell death
- an energy-dependent process specifically designed to switch off unneeded or damaged cells and eliminate them
How can Apoptosis occur?
- Physiological
- Pathological
What is Physiological Apoptosis?
- during embryogenesis is shaping of fingers and toes
- physiological involution of the thymus during development or the endometrium during the menstrual cycle
- removal of an infected or damaged cell
What is Pathological Apoptosis?
- following radiation injury
- some cancers
How do Apoptotic cells initiate their own death?
by the activation of proteases that breakdown the cell nucleus and cytoskeleton
What occurs in Apoptosis?
- The cell nucleus collapses due to chromatin condensation and fragmentation
- the cell then shrinks and is cleaved into cytoplasmic buds enclosing organelles
- finally, phagocytosis of the extruded apoptotic bodies
What are the signs of necrosis?
- chromatin clumping
- organelle swelling
- membrane damage
