Lectures 28+29 Learning Objectives (Hudmon) Flashcards
Understand how cells respond to injury (entire process)
A normal cell goes through homeostasis but when homeostasis is disrupted it can go through different pathways. When the cell goes through stress on increased demand, it can go through adaptation. If it cannot adapt, it will suffer cell injury. Cell injury leads to reversible injury or subcellular alterations. If the cell finds itself at a point of irreversibility, it will go through necrosis. The cell could also go through apoptosis.
Atrophy
**SIZE! **Cell shrinkage.
Caused by:
-decreased workload
-loss of innervation
-reduced blood supply
-inadequate nutrition
-aging (sterile atrophy)
Increasing protein degradation or reducing protein synthesis decreases cell size!
Hypertrophy
SIZE! Cells get bigger.
Typically caused by increased workload
Pathological hypertrophy (hypertension, aortic valve) can lead to decompensation.
Hyperplasia
NUMBER! More cells, cells are dividing
Pathological results from excessive hormonal or growth factors or tissue may eventually become malignant.
Physiological can be the proliferation of connective tissue cells during wound healing.
Metaplasia
FORM! Cell turns into a different form and it is reversible.
This is a response to chronic inflammation and irritation
Metaplasia is a precursor to malignancy.
Barrett’s Esophagus is a good example of metaplasia:
-normal columnar cells to squamous epithelium cells because of stomach acid damaging the esophagus
Dysplasia
ORGANIZATION! Uncontrolled growth. Unorganized.
Associated with chronic irritation and inflammation.
Often happens in the respiratory tract and uterine cervix.
Can be both R and IR
Dysplasia is strongly implicated as a precursor of cancer
Cause of cell injury: Oxygen Deprivation
A cause of cell injury
Hypoxia is an oxygen deficiency
Ischemia is loss of oxygenated blood supply to tissues
Cause of cell injury: Chemical agents
A cause of cell injury
Poisons, air pollutants, CO, and asbestos
Cause of cell injury: Infectious agents
A cause of cell injury
Viruses, bacteria, fungi, and parasites
Cause of cell injury: Immunological reactions
A cause of cell injury
Autoimmune diseases
Cause of cell injury: Genetic defects
A cause of cell injury
Sickle cell anemia, familial hypercholesterolemia
Cause of cell injury: Physical agents
A cause of cell injury
Trauma, heat, cold, electric shock
Cause of cell injury: Nutritional Imbalances
A cause of cell injury
Nutritional deficiencies- caloric or vitamin
Excess nutrition
Diabetes
Atherosclerosis
Cause of cell injury: Aging
A cause of cell injury
Accumulation of damage by ROS, loss of telomerase function
Reversible Injury
- Cellular swelling is the result of the failure of energy-dependent ion pumps in the plasma membrane which enables homeostasis.
- Fatty changes when there is the appearance of small or large lipid vaculoes in the cytoplasm.
Reversible cell injury can recover back to normal cells!
Irreversible Injury
- The inability to reverse mitochondrial dysfunction (lack of oxidative phosphorylation and ATP generation)
- Profound disturbances in membrane function
Irreversible injury leads to necrosis.
ATP Depletion mechanism
- Ischemia (insufficient O2 to tissues)
- oxidative phosphorylation in mitochondria DECREASES
- DECREASE in ATP
-A decrease in ATP can cause a decrease in the sodium pump which will increase calcium, water, and sodium IN the cell and increase potassium OUT the cell. This will cause ER swelling, cellular swelling, loss of microvilli, and blebs.
-A decrease in ATP can also cause an increase in anaerobic glycolysis which will cause a decrease of glycogen and an increase in lactic acid. An increase in lactic acid will lower pH and clump nuclear chromatin.
-ATP decrease will lastly cause detachment of ribosomes which lower protein synthesis.
Damage to mitochondria mechanism
Disregulated calcium signaling is the main way for mitochondrial damage.
If mitochondria release hydrogen, it will lead to necrosis.
If mitochondria release cytochrome C, it will lead to apoptosis.
Membrane damage mechanism
Phospholipid loss, lipid breakdown products, and cytoskeletal damage all lead to membrane damage.
Calcium influx mechanism
Cause of increase in cytosolic calcium concentration is because of release from intracellular calcium stores and calcium influx across the plasma membrane.
The activation of various enzymes causes the mechanism of damage.
Too much calcium leads to:
-mitochondrial damage
-ER damage
-all the proteins get activated when they shouldn’t
Increase of ROS (reactive oxygen species) damages mechanism
???
Intrinsic Pathway (mechanism)
Apoptotic pathway!
A process where the cell self-destructs in response to internal stress, like DNA damage or lack of survival signals.
It starts with mitochondria.
Extrinsic pathway (mechanism)
Apoptotic pathway!
Triggered by signals outside the cell.
Apoptosis
PROGRAMMED CELL DEATH
